Headcount: 23,000
Revenues: $28,190 (+7%)
Net Income: $6,717 (+3%)
R&D: $4,784 (+8%)

Amgen performed well in 2023, advancing many promising molecules in its pipeline, completing a significant acquisition and delivering strong financial performance.

Total revenues in 2023 increased 7% from the prior year to $28.2 billion. Demand for Amgen’s products was strong resulting in 15% volume growth, partially offset by a 3% decline in net selling price. Eighteen medicines generated record sales in 2023, and nine had sales exceeding $1 billion.

Amgen’s performance last year included $954 million in sales associated with its acquisition of Horizon Therapeutics plc, a provider of medicines to treat rare inflammatory diseases, which Amgen completed on October 6, 2023 for approximately $27.8 billion. There were some roadblocks along the way, such as an FTC administrative lawsuit which needed to be resolved, but the strategic and financial rationale for the acquisition is undeniable. The acquisition strengthens Amgen’s inflammation portfolio by adding first-in-class, early-in-lifecycle medicines such as Tepezza (teprotumumab-trbw), Krystexxa (pegloticase) and Uplizna (inebilizumab-cdon), which treat rare inflammatory diseases. Furthermore, the deal aligns with Amgen’s core strategy of delivering innovative medicines that make a significant difference for serious diseases.

Further underscoring the company’s commitment to the advancement of its robust pipeline and ongoing scientific and technological innovation, Amgen made two changes to its senior leadership team in the areas of research and development (R&D) and technology. James Bradner, M.D., joined Amgen as executive vice president of research and development, and chief scientific officer. Bradner is a physician-scientist and a seasoned R&D leader, having previously served as president of the Novartis Institutes for BioMedical Research. He succeeds David M. Reese, M.D., who was appointed executive vice president and chief technology officer. Reese has been with Amgen for nearly 20 years and has led its R&D organization since 2018.

Both Bradner and Reese will report to Robert A. Bradway, chairman and chief executive officer at Amgen. According to Bradway, these appointments “reflect our conviction that the rapid convergence of ‘biotech’ and ‘tech’ will unlock the next frontier of innovation in biotechnology.”

In positive pipeline news, the FDA approved the supplemental Biologics License Application (sBLA) for Blincyto (blinatumomab) for the treatment of adults and pediatric patients with CD19-positive B-cell precursor acute lymphoblastic leukemia (B-ALL) in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1%, based on additional data from two Phase 3 studies that were submitted. The approval converts Blincyto’s accelerated approval to a full approval.

The FDA also approved Blincyto for the treatment of adult and pediatric patients one month or older with CD19-positive Philadelphia chromosome-negative B-ALL in the consolidation phase, regardless of measurable residual disease (MRD) status.

Imdelltra (tarlatamab-dlle) was approved by the FDA for the treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy. Imdelltra is the first and only DLL3-targeting Bispecific T-cell Engager therapy that activates the patient’s own T cells to attack DLL3-expressing tumor cells.

R&D Collaborations

Amgen frequently enters into business relationships, including joint ventures and collaborative arrangements, for the R&D, manufacture and/or commercialization of products and/or product candidates. For example, the company is in a collaboration with AstraZeneca for the development and commercialization of Tezspire and a collaboration with UCB for the development and commercialization of Evenity.

In September 2023, the company introduced Amgen Partners of Choice, a new network that brings together Amgen’s oncology research and development experts and clinical leaders at eight research centers across the globe. As part of Amgen’s mission to improve care through partnerships across the healthcare ecosystem, the network fosters academic collaboration to advance new treatment options for patients with the greatest unmet needs. The network aims to create multiple collaboration channels globally with the goal of expediting the transition of new, transformational programs to leaders in the clinic. Current Amgen Partners of Choice projects are focused on select disease areas and tumor types including thoracic, gastrointestinal and genitourinary cancers.

Facility Investments

In February 2024, Amgen opened its manufacturing site in Central Ohio, the newest in its global operations network and its most advanced facility to date.

The nearly 300,000-square-foot facility will employ 400 full-time staff. It also features open workspaces to foster collaboration and has been designed to meet the highest environmental sustainability standards, in support of Amgen’s commitment to achieve carbon neutrality for all operations by 2027.

In partnership with Columbus State Community College, Amgen is hosting an inaugural 18-month manufacturing apprenticeship at the site. This program, designed for those new to the field or changing careers, offers a blend of classroom and practical training, aiming to expand opportunities for skilled individuals without the requirement for a formal bachelor’s degree.

The company believes in the importance of nurturing and inspiring the next generation of innovators. That’s why the Amgen Foundation has invested nearly $270 million over more than 30 years to provide best-in-class, no-cost science education programs that now reach approximately 25 million students annually around the world.

In 2023, the Amgen Foundation announced a new investment of more than $12 million to expand the Amgen Biotech Experience (ABE), a free science education program that has provided nearly a million high school students globally with hands-on biotech experiences. The new funding will be used to bring ABE to communities in Brazil, Mexico and South Africa, with the goal of reaching an additional 180,000 students over the next two years.

Also, last year the Amgen Foundation committed over $8 million in new funding to the Amgen Scholars Program, an undergraduate summer research experience hosted at premier educational institutions around the world. More than 5,300 students have completed the program to date, and this new investment will enable an additional 500 students to participate over the next two years.

Looking forward, the company expects total revenues in the range of $32.5 billion to $33.8 billion for the full year 2024. For the first quarter of 2024, total revenues increased 22% to $7.4 billion in comparison to the first quarter of 2023.

“With many of our innovative products delivering strong growth and promising new medicines advancing through our pipeline, we are excited about delivering attractive long-term growth,” said Bradway.

Headcount: 25,200
Revenues: $26,323 (+1%)
Net Income: $6,552 (+11%)
R&D: $1,324 (-2%)

It was a good year for Amgen despite sales being relatively flat, growing just 1% to $26.3 billion. Several medicines performed particularly well last year, including the cholesterol treatment Repatha (sales +16% versus the prior year), osteoporosis medicines Evenity (+48%) and Prolia (+12%), and several oncology and hematology therapies, such as Nplate (+27%), Blincyto (+24%), and Kyprolis (+13%). Two of Amgen’s newest innovations—Lumakras/Lumykras to treat a type of non-small cell lung cancer and Tezspire to treat severe asthma—collectively contributed more than $450 million in 2022 sales.

In positive pipeline news, FDA granted full approval to Blincyto for a new indication in Leukemia treatment. Riabni, a biosimilar to arthritis drug Rituxan, received FDA approval and to treat all available Rituxan indications and is Amgen’s fifth FDA-approved biosimilar.

Blockbuster Horizon deal

Compared to prior years, 2022 was shaping up to be a lackluster year for biopharma M&A. However, just before the year closed out, in December, Amgen struck a blockbuster deal—the largest of the year—to acquire Ireland-based Horizon Therapeutics for around $28 billion, strengthening its portfolio of treatments for rare, autoimmune, and severe inflammatory diseases.

The deal was also a way for Amgen to shore up losses when its top seller, arthritis drug Enbrel, faced the start of its loss of exclusivity on June 8, 2023. Sales of Enbrel fell 8% to $4.1 billion in 2022 and have continued to slide. According to first quarter 2023 data, Enbrel’s U.S. sales tumbled 33% year-over-year to $564 million.

Among the marketed products that Amgen gains through the Horizon purchase are thyroid eye disease drug Tepezza, gout therapy Krystexxa, and Uplizna. The three drugs carry promising growth potential. Horizon reported at the end of last year that Tepezza’s peak sales estimate are more than $4 billion and Krystexxa’s U.S. peak sales expectations are greater than $1.5 billion. As for Uplizna, the drug is FDA-approved in neuromyelitis optica spectrum disorder and is in clinical testing in some other increasingly competitive rare autoimmune indications such as myasthenia gravis.

Amgen hoped to complete the acquisition in the first half of this year, but at time of press, the deal has yet to get the green light from regulators. In fact, at the request of the U.S. Federal Trade Commission (FTC), Amgen agreed to delay closure of the deal until September 2023. The move comes in response to the FTC filing an antitrust lawsuit in May which is attempting to block the sale.

In other acquisition news, Amgen entered a deal earlier in the year for ChemoCentryx. It paid $3.7 billion in August 2022 for the rare diseases firm and in so doing added the investigational drug Tavneos, a transformative, first-in-class treatment for ANCA-associated vasculitis, to its portfolio. The drug generated $21 million of sales in the fourth quarter last year. In addition to Tavneos, the acquisition adds three early-stage drug candidates that target chemoattractant receptors and other inflammatory diseases and an oral checkpoint for cancer.

R&D collaborations

Recognizing the unique discovery challenges in multispecific drug discovery, Amgen has invested over the last decade in the marriage of wet lab high throughput automation and dry lab computational biology. Amgen’s generative biology strategy has led to the building of a Digital Biologics Discovery group.The goal is to leverage biologics expertise with emerging sequence-based drug design technologies to deliver complex multispecific medicines against a variety of difficult-to-treat diseases.

To this end, Amgen and Generate Biomedicines entered a research collaboration to create protein therapeutics for five clinical targets across several therapeutic areas and multiple modalities. Amgen paid $50 million in upfront funding for the initial five programs with a potential transaction value of $1.9 billion plus future royalties. Combining its drug discovery expertise with Generate Biomedicines’ AI platform provides the opportunity to further facilitate multispecific drug design by shaving time off discovery timelines and generating potential lead molecules that have predictable manufacturability and clinical behavior.

In another AI deal, Owkin and Amgen announced results of a three-year project leveraging artificial intelligence to more accurately predict cardiovascular risk. This study demonstrates the ability of AI to improve the way clinicians predict patients’ risk of suffering major cardiovascular events, such as strokes and myocardial infarctions.

The goal is to better predict which patients will suffer major cardiovascular events and improve both patient outcomes and efficiency. Identifying at-risk patients sooner will allow them to benefit from better care, adapted to their individual risk profile. With electronic medical records being complete and more prevalent, the use of machine learning aims to better predict cardiovascular risk and could have wide application. Owkin and Amgen have been collaborating for five years on projects across cardiology, hematology and oncology to develop clinical applications for artificial intelligence.

In another research pact, Amgen and Arrakis Therapeutics formed a collaboration focused on the discovery and development of RNA degrader therapeutics against a range of difficult-to-drug targets in multiple therapeutic areas. This new class of “targeted RNA degraders” consists of small molecule drugs that selectively destroy RNAs encoding disease-causing proteins by inducing their proximity to nucleases.

With its partner Syngene International, a research, development and manufacturing services company, Amgen extended its long-standing multi-discipline research collaboration. The contract is currently extended until the end of 2026 and its scope includes drug discovery and development solutions in chemistry and biology, peptide chemistry, antibody and protein reagents, pharmacokinetics and drug metabolism, and pharmaceutical development. In addition to operating the existing Syngene Amgen R&D Center (SARC), under the new contract, Syngene will also build and operate a dedicated lab to enable R&D project acceleration. SARC was established in 2016 and Syngene announced expansion of the original dedicated center in 2017. It currently consists of 60,000 square-feet of floor space and a dedicated team of multi-disciplinary Syngene scientists who work closely with Amgen researchers around the world.

Facility investments

In March 2022, Amgen broke ground at its newest biomanufacturing facility in Holly Springs, NC. The facility, expected to be operational by 2025, will support Amgen’s medicines that treat illnesses such as cancer and heart disease. The facility will use new technologies that maximize efficiency and help ensure the ability to produce a broad range of medicines.

Later in the year, in October, Amgen opened a new research and development site in San Francisco’s Oyster Point, continuing the company’s nearly two-decade presence in the region.

The new site will constitute the company’s second largest research and development facility, which focuses on discovering therapeutics for patients living with cancer, inflammatory disease and cardiometabolic disorders. The centerpiece of the new site is a 245,000 square foot, nine-story building that will provide a workplace for 650 staff representing 24 different functions.

In other facility news, towards the end of 2021, Amgen unveiled plans for a $365 million site investment, breaking ground on a biomanufacturing plant in New Albany, OH. The final product assembly and packaging plant will support production of medicines for the U.S. and is expected to be operational by 2024.

Headcount: 24,200
Revenues: $25,970 (+2%)
Net Income: $5,893 (-19%)
R&D: $4,818 (+15%)

TOP SELLING DRUGS 

As the company sees a gradual recovery from the Covid-19 pandemic, with patient visits and diagnosis rates approaching pre-pandemic levels by early in the fourth quarter, product sales for the year were flat, with 7% growth in unit volumes offset by a 7% decline in net selling price. Modest growth for the year was driven by increased revenue from Amgen’s global antibody manufacturing collaboration for Lilly’s Covid-19 therapies, and earnings for the year were impacted by the write-off of $1.5 billion in acquired in-process research & development associated with the acquisition of Five Prime Therapeutics.

Established products, which include Neulasta, Neupogen, Epogen, Aranesp, Parsabiv, and Sensipar/Mimpara, were down 25% for the year, primarily driven by volume declines and lower net selling price. The average selling price for Neulasta in the U.S. declined 38%, and going forward, additional price and volume erosion is expected across this portfolio of products.

In the fourth quarter, Enbrel saw its third consecutive quarter of volume declines, and sales for the year were down 11%. In 2022, Enbrel’s net selling price is expected to continue to decline.

Meanwhile, Amgen’s next top seller, Prolia achieved 18% sales growth driven by an increase in both new and repeat patients. Repatha’s 26% sales increase and volume growth of 40% for the year was partially offset by lower net selling price. For 2021, Repatha remained the global proprotein convertase subtilisin/kexin type 9 (PCSK9) segment leader, with more than 1 million patients treated since launch. Also, Nplate enjoyed a 15% volume growth with sales reaching $1 billion, up 21%.

Finally, joining Amgen’s top 10, multi-billion-dollar products, Mvasi (biosimilar to Avastin) had revenues nearing $1.2 billion. The drug is approved for all eligible indications of the reference product, Avastin. In the U.S. Mvasi is the first anti-cancer biosimilar, as well as the first bevacizumab biosimilar, approved by the FDA. Mvasi is approved for the treatment of five types of cancer, including non-squamous non-small cell lung cancer (NSCLC), metastatic colorectal cancer (mCRC), glioblastoma, kidney cancer and cervical cancer.

Business ventures

This past March, Amgen initiated construction of its newest biomanufacturing facility in Holly Springs, NC. The facility, expected to be operational by 2025, will support the growing demand for Amgen’s medicines that treat serious illnesses such as cancer and heart disease. The facility will leverage new technologies that aim to maximize efficiency and help ensure the ability to produce a broad range of medicines.

In October, Amgen completed its acquisition of Teneobio, Inc. for $900 million upfront in cash, as well as future contingent milestone payments worth up to an additional $1.6 billion in cash. The acquisition includes Teneobio’s bispecific and multispecific antibody technologies, which Amgen hopes to enable significant acceleration and efficiency in the discovery and development of new molecules across its core therapeutic areas. The acquisition also adds TNB-585, a Phase 1 bispecific T cell engager for the treatment of metastatic castrate-resistant prostate cancer, and several preclinical oncology assets with the potential for near-term Investigational New Drug (IND) filings.

Alliances

Throughout the year, Amgen invested in partnerships in an effort to advance protein degradation therapeutics for challenging drug targets, to develop targeted RNA degraders, and protein therapeutics leveraging machine learning.

An exclusive, worldwide, multi-year research collaboration and license agreement with Plexium, Inc. aims to identify novel targeted protein degradation therapeutics for historically challenging drug targets. The collaboration supports the discovery of novel molecular glue therapeutics and will initially focus on two programs. Plexium is eligible to receive more than $500 million in success-based development, regulatory and commercial milestones, as well as royalty payments. Amgen has a commercial license to each program that advances and will be responsible for global development and commercialization.

A research collaboration with Arrakis Therapeutics is focused on the discovery and development of RNA degrader therapeutics against a range of difficult-to-drug targets in multiple therapeutic areas. This new class of “targeted RNA degraders” consists of small molecule drugs that selectively destroy RNAs encoding disease-causing proteins by inducing their proximity to nucleases. Arrakis will lead research activities for the identification of RNA-targeted small molecule (rSM) binders against targets selected by Amgen. Amgen will pay $75 million upfront to Arrakis for five initial programs, and Arrakis will be eligible for additional payments, which could potentially reach several billion dollars in future payments if all milestones are met and future program options are exercised.

Another research pact with Generate Biomedicines aims to discover and create protein therapeutics for five clinical targets across several therapeutic areas and multiple modalities, leveraging Generate’s machine learning-enabled technology platform. Amgen will pay $50 million upfront with a potential transaction value of $1.9 billion plus future royalties. For each program, Amgen will pay up to $370 million in future milestones and royalties.

Finally, a strategic collaboration with Neumora Therapeutics, Inc., a biopharmaceutical company pioneering precision medicines for brain diseases, aims to advance neuroscience discovery, development and commercialization.

The companies will collaborate on programs by applying Neumora’s precision neuroscience platform to insights generated by Amgen’s deCODE genetics and human data research capabilities. In addition, Amgen made a $100 million equity investment in Neumora and provided exclusive global rights to develop and commercialize Amgen programs targeting casein kinase 1 delta and glucocerebrosidase for neurodegenerative diseases.

R&D advances and approvals

Amgen won several approvals for new products and expanded indications for existing products. The FDA approved Otezla (apremilast) for the treatment of adult patients with plaque psoriasis who are candidates for phototherapy or systemic therapy. With this expanded indication, Otezla is now the first and only oral treatment approved in plaque psoriasis across all severities, including mild, moderate and severe.

The FDA also approved Amgen and AstraZeneca’s Tezspire (tezepelumab-ekko) for the add-on maintenance treatment of adult and pediatric patients aged 12 and older with severe asthma, becoming first and only biologic to consistently and significantly reduce exacerbations in patients with severe asthma.

Meanwhile, an expanded approval for Kyprolis in combination with subcutaneous treatment regimen provides further options for patients with relapsed/refractory multiple myeloma.

Repatha received approval from the FDA as an adjunct to diet and other low-density lipoprotein cholesterol (LDL-C)-lowering therapies for the treatment of pediatric patients aged 10 years and older with heterozygous familial hypercholesterolemia (HeFH) to reduce LDL-C. HeFH is an inherited, genetic condition with a prevalence of one in 250 people worldwide.

Amgen’s fifth FDA-approved biosimilar is now approved to treat all available Rituxan indications. Recently, the FDA approved Riabni (rituximab-arrx), in combination with methotrexate in moderate to severely active rheumatoid arthritis with an inadequate response to one or more tumor necrosis factor antagonist therapies. Riabni is already approved for the treatment of non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, Wegener’s granulomatosis, and microscopic polyangiitis.

Finally, offering hope in pancreatic cancer, Lumakras (sotorasib), in the largest dataset and only global clinical trial to date evaluating the efficacy and safety of a KRAS G12C inhibitor in advanced pancreatic cancer, demonstrated centrally confirmed objective response rate of 21% and an impressive disease control rate of 84%. In the Phase 1/2 trial data showed encouraging and clinically meaningful anticancer activity and a positive benefit/risk profile across 38 heavily pre-treated advanced pancreatic cancer patients.

Lumakras was recently approved in Japan for the treatment of KRAS G12C-mutated positive, unresectable, advanced and/or recurrent non-small cell lung cancer that has progressed after systemic anticancer therapy. Lumakras was previously approved by the FDA in May 2021.

Headcount: 24,000
Pharma Revenues: $25,424 (+9%)
Net Income: $7,264 (-7%)
R&D: $4,085 (+7%)

TOP SELLING DRUGS

2020 was a successful year for Amgen, with growth for many newer medicines, including cholesterol treatment Repatha (+34%), migraine therapy Aimovig (+24%), and osteoporosis drug EVENITY (+85%). Product sales increased 9% for the year driven by 15% volume growth. Sales in the U.S. grew 9%, sales outside the U.S. grew 10%, and revenues in the Asia-Pacific region exceeded $1 billion for the first time.

Also adding significant revenue, Amgen integrated Otezla, which was acquired from Celgene in November 2019, strengthening its leadership position in inflammation. Otezla generated sales of $2.2 billion in 2020 and it’s expected to be strong growth driver for several years to come.

With four Amgen biosimilars now available, biosimilars sales grew to $1.7 billion. The most recent addition RIABNI, was approved in the U.S. in December 2020 as a biosimilar to Roche’s cancer drug Rituxan. Three additional biosimilars are in Phase 3 development.

Amgen has high hopes for two products in particular, sotorasib for non-small cell lung cancer and tezepelumab for severe asthma. Sotorasib holds a great deal of promise in treating non-small cell lung cancer and other solid tumors harboring the KRASG12C mutation. Until now, KRASG12C protein was long considered an “undruggable” target. Additionally, tezepelumab is a potential first-in-class human monoclonal antibody that targets a protein associated with multiple inflammatory cascades critical in the initiation and persistence of airway inflammation associated with severe asthma. Unlike existing treatments, tezepelumab is the first biologic shown to consistently and significantly reduce exacerbations in a broad population of severe asthma patients.

In 2020, Amgen and AstraZeneca updated their 2012 collaboration agreement for tezepelumab and will continue to share costs and profits equally after AstraZeneca pays an inventor royalty to Amgen.

In a big win for Amgen, last July, the U.S. Court of Appeals for the Federal Circuit held in Amgen’s favor on the validity of two Enbrel patents and methods for making it.

Investment endeavors
This past March, Amgen entered an agreement to acquire Five Prime Therapeutics for approximately $1.9 billion, expanding its oncology portfolio with Five Prime’s lead asset, bemarituzumab, a first-in-class, Phase 3 ready anti-FGFR2b antibody with positive Phase 2 results in advanced gastric cancer. Bemarituzumab targets FGFR2b, which has been found to be overexpressed in approximately 30% of patients with non-HER2 positive gastric cancer, as well as other solid tumors. This correlation suggests that FGFR2b could play a role in other epithelial cancers, including lung, breast, ovarian and other cancers.

The acquisition also supports Amgen’s international expansion strategy. Gastric cancer is one of the world’s most common forms of cancer and is particularly prevalent in the Asia-Pacific region, where Amgen plans to leverage its presence in Japan and other Asia-Pacific markets to maximize bemarituzumab’s potential.

Amgen previously had purchased from Astellas 49% of shares of Amgen Astellas BioPharma K.K. (AABP), a joint venture between the companies dating back to 2013. AABP is now a wholly-owned Amgen affiliate in Japan renamed Amgen K.K. and established Amgen’s presence in the country.

Also this past March, for a $55 million upfront and future milestones potentially worth an additional $666 million, Amgen acquired Rodeo Therapeutics, a biopharmaceutical company based in Seattle that develops small-molecule therapies designed to promote regeneration and repair of multiple tissues. Rodeo’s 15-PGDH program expands Amgen’s inflammation portfolio and efforts to develop first-in-class therapeutics. Rodeo’s lead 15-prostaglandin dehydrogenase (15-PGDH) modulators have generated compelling data in preclinical studies and have clinical potential in multiple indications.

Back in July, Amgen made an additional investment of approximately $421 million in BeiGene, which maintains Amgen’s current ownership of BeiGene of approximately 20%. This additional investment reflects Amgen’s confidence in the progress the companies are making in their ongoing oncology collaboration in China.

R&D
Several assets advanced this past year with a key approval for Lumakras, in addition to late-stage pipeline assets that include several potential new medicines in Phase 2 development for the treatment of atherosclerosis, systemic lupus erythematosus, and celiac disease.

The FDA recently approved Amgen’s KRAS-blocking drug Lumakras (sotorasib) for patients with advanced lung cancer. The drug is the first medicine approved to target the KRAS gene, which is frequently mutated in lung, colon and pancreatic cancers. Decades of research went into developing treatments that block the mutated gene’s effects, and now those efforts have proved successful.

Amgen and partner AstraZeneca recently submitted a Biologics License Application to the FDA for tezepelumab in severe asthma. The submission is supported by positive clinical trial results which demonstrated a statistically significant and clinically meaningful reduction in the annualized asthma exacerbation rate in patients with severe, uncontrolled asthma compared to placebo.

Meanwhile, Amgen’s investigational targeted treatment Bemarituzumab was granted breakthrough therapy designation as first-line targeted therapy for tumors that overexpress FGFR2b in gastric and gastroesophageal junction cancers, in combination with modified FOLFOX6, based on an FDA-approved companion diagnostic. Following sotorasib, bemarituzumab was the second Amgen oncology asset to receive the designation in the past six months.

Amgen and Kyowa Kirin Co. partnered to develop and commercialize KHK4083, Kyowa Kirin’s potential first-in-class, Phase 3-ready anti-OX40 fully human monoclonal antibody in development for the treatment of atopic dermatitis, with potential in other autoimmune diseases. KHK4083 has been shown to selectively deplete activated T cells that are critical in the development of atopic dermatitis. Amgen will lead the development, manufacturing, and commercialization for KHK4083 for all markets globally, except Japan. Amgen paid $400 million upfront and will pay up to an additional $850 million in potential milestones. Amgen will leverage unique data from its deCODE Genetics subsidiary for the potential use of KHK4083 in other indications.

In other asset news, Amgen and Medicines Development for Global Health (MDGH), entered a license agreement for AMG 634, a phosphodiesterase type 4 (PDE4) inhibitor being investigated in Phase 2 trials for the treatment of tuberculosis (TB) and erythema nodosum leprosum, an inflammatory skin and systemic complication of leprosy.  Amgen had acquired AMG 634 as part of its acquisition of Otezla from Celgene in 2019. MDGH will assume full responsibility for the further development and commercialization of AMG 634.

Lastly, Amgen terminated its collaboration with Cytokinetics and transitioned the development and commercialization rights for omecamtiv mecarbil and AMG 594 to Cytokinetics. Omecamtiv mecarbil, an investigational selective cardiac myosin activator, is being studied chronic heart failure, and AMG 594, a novel mechanism selective cardiac troponin activator, is in Phase 1 development other types of heart failure.

COVID efforts
An alliance with the Global Coalition for Adaptive Research (GCAR) and Lilly aims to support global COVID efforts. The collaboration with GCAR and Eisai Co., Ltd. is studying the immune modulation in COVID, testing multiple interventions for the treatment of patients hospitalized with COVID-19. Amgen’s apremilast and Eisai’s investigational eritoran are being evaluated as potential therapeutic agents.

Amgen’s apremilast is an oral drug which inhibits the activity of PDE4 (Phosphodiesterase 4), an enzyme found in inflammatory cells. By inhibiting PDE4, apremilast is thought to modulate the production of inflammatory cytokines and other mediators, which may prove helpful in inhibiting the inflammatory response associated with the signs, symptoms and pulmonary involvements observed in some COVID-19 patients. Apremilast is currently approved for use in more than 45 countries as an oral treatment for inflammatory diseases including moderate to severe plaque psoriasis, psoriatic arthritis and oral ulcers associated with Behcet’s disease.

Finally, a global antibody manufacturing collaboration with Eli Lilly and Co. aims to significantly increase the supply capacity available for Lilly’s COVID-19 therapies Bamlanivimab and Etesevimab, which were recently authorized by the FDA under an Emergency Use Authorization. Through this collaboration, the two companies will have the ability to quickly scale up production and serve more patients globally.

Headcount: 22,000
Revenues: $23,362 (-2%)
Net Income: $7,842 (-7%)
R&D: $4,116 (+10%)

TOP SELLING DRUGS

In 2019, Amgen’s newer drugs continued to drive growth, though not enough to offset revenues falling 2% to $23.4 billion. To bolster its portfolio, Amgen executed a major deal during the year to expand its inflammation franchise when it agreed to pay $13.4 billion for Celgene’s Otezla (apremilast), the only oral, non-biologic treatment for psoriasis and psoriatic arthritis. Amgen said that the acquisition is a strong strategic fit with its inflammation franchise offering a differentiated, oral therapy, along with Otezla’s sales growth potential over the next five years. Sales of Otezla in 2018 were $1.6 billion.

Otezla is currently approved for three indications in the U.S., including patients with moderate-to-severe plaque psoriasis who are candidates for phototherapy or systemic therapy; adult patients with active psoriatic arthritis; and adult patients with oral ulcers associated with Behçet’s Disease. Otezla is approved in more than 50 markets outside the U.S., including the EU and Japan, and has patent exclusivity through at least 2028 in the U.S.

More positive news was reported in 2019 when Amgen launched Evenity, the first and only osteoporosis treatment that both increases bone formation and reduces bone loss, thereby rapidly reducing the risk of fracture.

China expansion plans unfold
Amgen made its intentions clear to expand in China when it entered into a strategic collaboration with BeiGene that will significantly accelerate its expansion plans in the country. BeiGene is a research-based, oncology-focused biotechnology company with an established and experienced team in China, including a 700-person commercial organization and a 600-person clinical development organization. As part of the collaboration Amgen paid $2.7 billion for a 20.5% stake in BeiGene.

Under the agreement, BeiGene will commercialize Xgeva, Kyprolis and Blincyto in China during which time the parties will equally share profits and losses. Two of these products will revert to Amgen, one after five years and one after seven years. Following the commercialization period, BeiGene will have the right to retain one product and will be entitled to receive royalties on sales in China for an additional five years on the products not retained. Xgeva was launched in China in September of 2019; Kyprolis and Blincyto are both in Phase 3 trials in China.

The two companies will collaborate to advance 20 medicines from Amgen’s innovative oncology pipeline in China and globally. BeiGene will share global research and development costs and contribute up to $1.25 billion to advance these medicines. Amgen will pay royalties to BeiGene on sales of these products outside of China, with the exception of AMG 510, Amgen’s first-in-class KRASG12C inhibitor that is being studied as a potential treatment for solid tumors.

Of the 20 oncology medicines, BeiGene will assume commercial rights in China for seven years after launch for those that receive approval in China, including AMG 510. After this time, BeiGene will retain rights to up to six of these products in China, excluding AMG 510, while rights on remaining products revert to Amgen.

Amgen will continue to commercialize its non-oncology product portfolio in China. Earlier this year, Amgen launched its first-ever product in China, Repatha, an LDL cholesterol-lowering treatment proven to reduce the risk of heart attacks and stroke. Amgen expects to launch a number of other non-oncology medicines in China over the next several years, including Prolia, which reduces the risk of fracture in postmenopausal women with osteoporosis.

Xgeva, Kyprolis and Blincyto, as well as the medicines in Amgen’s oncology pipeline, will be manufactured at Amgen’s existing facilities.

Drug discovery and research
To boost its drug discovery platform, in 2019 Amgen acquired Copenhagen, Denmark-based Nuevolution, for $167 million. Now called Amgen Research Copenhagen, the company has developed Chemetics,  a pioneering technology in the emerging field of DNA-encoded libraries. In a DNA-encoded library, each compound is tagged with a unique sequence of DNA that functions like a barcode, and mixtures containing billions of unique DNA-tagged compounds can be screened in a single small test tube, according to the company.

In a research collaboration, Amgen and Syapse, a precision medicine insight company, entered a partnership to develop observational research analytics to assess treatment outcomes for areas of unmet need in oncology.
This effort aims to identify existing patients within the Syapse Learning Health Network that could be eligible for Amgen-sponsored clinical trials and to bring these trials to community health system sites. The companies will create opportunities for physicians and researchers within the Syapse Network to gain access to analytics, real-world evidence-based insights, and collaborative research opportunities.

Amgen will have access to real-world evidence for potential use in regulatory filings in support of certain agreed upon development candidates in oncology. Amgen will also work with Syapse to develop real-world evidence standards to support the acceleration of therapies to market.

In another research tie-up, Amgen and the University of Washington’s Institute for Protein Design (IPD) entered a broad collaboration that will cover multiple projects with a goal of testing new technologies and creating protein-building approaches that can be broadly applied to drug research.

This will include optimizing Amgen’s repertoire of BiTE (bispecific T cell engager) antibodies, with the goal of expanding the types of tumors that can be targeted with these molecules. IPD’s expertise could also help Amgen to generate antibodies against very challenging drug targets and to devise new ways to modulate the activity of the immune system. In the longer-term, the broad-based collaboration could help shape the discovery and development of protein-based therapies.

To further enhance its R&D capabilities, at the end of the year, Amgen signed a lease with BioMed Realty for a new 240,000-square-foot Leadership in Energy and Environmental Design (LEED) candidate facility in the Gateway of Pacific campus development in South San Francisco. The new location, currently under construction at Oyster Point, will house Amgen’s Bay Area employees focused on cardiometabolic, inflammation and oncology, research. The new site will include modular green wet labs and green molecular lab design and is scheduled to open in early 2022.

Headcount: 21,500
Revenues: $23,747 (+4%)
Net Income: $8,394 (NM)
R&D: $1,182 (+13%)

TOP SELLING DRUGS 

While Amgen’s newer drugs Prolia, Xgeva, Blincyto, Kyprolis continue to drive growth, its mature flagship products are facing rising competition. Sales of Neulasta and Neupogen are declining due to biosimilar competition from several companies, including Mylan and Coherus BioSciences. Several others face generic competition as well, including Enbrel, Aranesp and Epogen. Meanwhile, sales of Amgen’s new migraine drug, Aimvoig, were unimpressive in the first quarter of 2019, and it’s up against strong competition from Lilly’s Emgality and Teva’s Ajovy.

Amgen is successfully advancing its pipeline with the approval of osteoporosis drug Evenity in April, and Kanjinti, a biosimilar of Roche’s breast cancer drug Herceptin, in June. This is the third biosimilar from Amgen’s portfolio to receive approval, providing the potential for long-term revenues. Amgen expects to launch additional biosimilars in 2019.

As part of an effort to bolster its R&D efforts, Amgen recently offered to acquire Nuevolution, a drug discovery platform biotech company based in Denmark, for approximately $167 million. The Nuevolution board has recommended accepting the offer and Amgen expects to settle by July 15.  The two companies have collaborated since October 2016 for drugs targeting multiple indications including two cancer programs. Having Nuevolution’s discovery platform in-house may aid Amgen’s discovery efforts for small molecules against difficult-to-drug targets and make the process more efficient.

Additionally, to further enhance its manufacturing capabilities, Amgen is expanding its campus in West Greenwich, RI with a new $160 million next-gen biomanufacturing plant that will be the first of its kind in the U.S. It will manufacture products for the U.S. and global markets. Amgen plans to incorporate multiple innovative technologies into a single facility, which is expected to be built in half the construction time with approximately half of the operating cost required of a traditional plant. Next generation biomanufacturing plants require a smaller manufacturing footprint offering environmental benefits such as reduced water and energy consumption, and lower levels of carbon emissions.

Among its more significant approvals, Amgen and UCB gained FDA approval for EVENITY for the treatment of osteoporosis in postmenopausal women at high risk for fracture. EVENITY is the first and only bone builder with a unique dual effect that both increases bone formation and to a lesser extent reduces bone resorption (or bone loss) to rapidly reduce the risk of fracture.

In October, the FDA approved the expanded indication for  KYPROLIS to include a once-weekly dosing option in combination with dexamethasone for patients with relapsed or refractory multiple myeloma. The approval was based on Phase III data demonstrating that KYPROLIS achieved superior progression-free survival and overall response rates, with a comparable safety profile, versus twice-weekly. The FDA reviewed the application under its Real-Time Oncology Review and Assessment Aid pilot programs, which aim to explore a more efficient review process to ensure that safe and effective treatments are available to patients as early as possible.

Also, Amgen’s BLINCYTO gained approval for relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) in Japan, and an expanded indication as a monotherapy to include adult patients with Philadelphia chromosome negative (Ph-) CD19 positive B-cell precursor acute lymphoblastic leukemia (ALL) by the European Commission. Developed by a joint venture between Amgen and Astellas Pharma Inc., BLINCYTO is the first-and-only bispecific T cell engager (BiTE) immunotherapy construct approved globally. It’s also the first approved immunotherapy from Amgen’s BiTE platform, an approach that helps the body’s immune system target cancer cells.

Amgen and its biosimilar partner Allergan, recently received approval from the FDA for Kanjinti, a biosimilar of Roche’s breast cancer drug, Herceptin, for all approved indications of the reference product, HER2 adjuvant and metastatic breast cancer, and HER2 metastatic gastric cancer or gastroesophageal junction adenocarcinoma. Since December of last year, the FDA approved four biosimilar versions of Herceptin including Kanjinti: Pfizer’s Trazimera, Merck/Samsung Bioepis’ Ontruzant, and Celltrion/Teva’s Herzuma).

Kanjinti is the third biosimilar from Amgen’s portfolio to receive approval in the U.S. and Europe, joining Amjevita (a biosimilar of Abbvie’s Humira) and Mvasi (a biosimilar of Roche’s cancer drug Avastin). Currently, Amgen has 10 biosimilar products in its portfolio and a biosimilar version of Johnson & Johnson/Merck’s Remicade (ABP 710) is under review in the U.S. and EU.

The collaboration with Allergan includes the development and commercialization of four oncology antibody biosimilars. A biosimilar version of Roche’s Rituxan is in late-stage development for non-Hodgkin’s lymphoma and rheumatoid arthritis.

Innovative oncology efforts are advancing as well. Amgen recently reported early data from a Phase I trial of AMG 510 showing promising activity in a study of 35 patients targeting one of the most commonly mutated genes in cancer. Analysts are suggesting it has the potential to be the next cancer blockbuster. Out of 10 lung cancer patients receiving Amgen’s AMG 510 in the early-stage study, five went into partial remission and another four saw their disease stabilize. One patient experienced a complete remission four months after treatment. Representing a 90% disease control rate which is quite remarkable for a Phase I trial.

MG 510 targets KRAS G12c mutation, which accounts for about 13% of non-small cell lung cancers and 3% to 5% of colorectal cancers, and has been the subject of research for decades. While Amgen’s results in colon cancer were less robust, it’s still too early to tell.

Furthermore, several interesting early research collaborations are underway. Most recently, a collaboration with Intermountain Health aims to rapidly develop new medicines. Amgen’s subsidiary deCODE genetics will have access to the genomes of 500,000 participants from a study carried out by Intermountain Healthcare. Amgen hopes to use this data to uncover new insights into specific diseases and develop new medicines that reach the right disease targets. The collaboration aims to improve success rates and reduce drug development cycle times. To date, Amgen has accelerated the development timeline from early preclinical work through clinical development with several of its molecules, including AMG 510, currently in Phase I.

In October, Amgen made an equity investment of $66 million in Oxford Nanopore Technologies, a UK-based company advancing a new generation of portable genetic sequencing technology to perform direct, real-time sequencing of DNA and RNA. deCODE Genetics uses Oxford’s sequencing technologies to conduct genome research, including the identification and validation of new targets. The investment aligns with Amgen’s strategic focus on using human genetics to develop new medicines.

Headcount: 20,800
Revenues: $22,849 (-1%)
Net Income: $1,979 (-74%)
R&D: $3,562 (-7%)

TOP SELLING DRUGS

Despite being a relatively flat year for Amgen financially—laden with competition and a net charge of $6.1 billion as a result of U.S. Tax Reform—it was in no way unproductive. Of its top 13 products, five saw declines, including flagship Enbrel, which began to decline in 2017 due to lower demand and selling price, and good old fashion competition—a trend that is expected to continue. Epogen also saw declines driven by selling price and, to a lesser extent, a shift in some U.S. dialysis centers to Aranesp. Also, Mylan’s recent approval of a biosimilar to Neulasta and other competition, is expected to eviscerate sales of Amgen’s cornerstone drug.

With many of Amgen’s key products facing patent expiry and increasing competition, the company has managed to simultaneously launch a number of new medicines. Recently launched products and new indications helped to offset the blow to flagship products, namely Prolia, which was just shy of reaching $2 billion, and Kyprolis, up 21% for the year.

Also, to help offset losses, Amgen has significantly reduced its facilities footprint globally, and is investing in capabilities to enable improvements and to respond quickly to a fast-changing, often unpredictable industry. Amgen has also expanded its geographic presence from approximately 50 countries to upwards of 100, in an effort to take advantage of global markets. One market of particular interest to Amgen is China, where the company is banking on launching its cholesterol drug Repatha to an estimated 450 million people in China with high cholesterol.

Notably, biologics manufacturing expertise is Amgen’s foundation, and recently the company received approval for commercial-scale production from multiple regulatory agencies for its next-gen biomanufacturing plant in Singapore. Also, in April, Amgen announced its expansion in RI with a new $160-million next-gen biomanufacturing plant that will be the first of its kind in the U.S. The company plans to incorporate several new technologies into a single facility, which is expected to be built in half the construction time with half of the operating cost of a traditional plant.

Amgen gained a flurry of approvals for new products and expanded indications for some of its top sellers. Securing the first-to-market position, the FDA recently approved Amgen’s Aimovig (erenumab-aooe) for the prevention of migraine. The self-administered, once monthly autoinjector, is a novel therapeutic approach and the first FDA-approved treatment specifically developed to prevent migraine by blocking the calcitonin gene-related peptide receptor (CGRP-R), which is believed to play a critical role in migraine. Aimovig is forecast to be the top-selling drug in the migraine market by 2026, generating an estimated $1.4 billion in sales in the seven major markets.

Prolia, which saw 20% growth this year, has recently been approved by the FDA and European Commission (EC) for the treatment of bone loss associated with long-term systemic glucocorticoid therapy in osteoporosis patients at increased risk of fracture.

Amgen also gained FDA approval to add overall survival for Kyprolis after data showed that Kyprolis, lenalidomide and dexamethasone (KRd) significantly reduced the risk of death by 21% and extended overall survival by 7.9 months versus lenalidomide and dexamethasone alone in relapsed/refractory multiple myeloma.

Among others, the EC recently approved an expanded indication for Xgeva for the prevention of skeletal-related events in advanced malignancies involving bone. In May, Amgen’s Repatha was approved by the FDA and EC to prevent heart attack and stroke. Repatha is the first PCSK9 inhibitor to prevent heart attacks, strokes and coronary revascularizations in adults with cardiovascular disease. Also, Blincyto picked up another indication for the treatment of B-cell precursor acute lymphoblastic leukemia based on response rate and relapse-free survival, making it the first FDA approved BiTE immunotherapy.

Recent R&D efforts include Amgen’s collaboration agreement with MD Anderson Cancer Center aimed at accelerating development of a variety of Amgen’s early-stage oncology therapies for leukemia, myelodysplastic syndromes, multiple myeloma, small-cell lung cancer, and other non-lung cancers with small-cell histologies. The agreements combine Amgen therapies nearing clinical development or those that have already begun the process with MD Anderson’s translational medicine capabilities. The collaboration will focus on Amgen’s BiTE, chimeric antigen receptor (CAR) T cell and small molecule programs.

Additionally, Amgen and Novartis expanded their collaboration with the Banner Alzheimer’s Institute to initiate a new Alzheimer’s prevention trial to determine whether the BACE1 inhibitor CNP520 can prevent or delay the onset of AD symptoms in a high-risk population.

Under an immuno-oncology collaboration with CytomX Therapeutics, the companies will co-develop a CytomX Probody T-cell engaging bispecific against the Epidermal Growth Factor Receptor (EGFR), an oncology target expressed on multiple cancers. Probody T-cell engaging bispecifics are antibody constructs capable of directing cytotoxic T-cells in tumor microenvironments.

Lastly, a collaboration with Array BioPharma for the discovery and development of novel drugs for autoimmune disorders will leverage Array’s platform in chemistry and early lead development.

Amgen’s biosimilar endeavors are beginning to bear fruit. This past January, Amgen and Allergan were granted marketing authorization by the EC for MVASI (biosimilar bevacizumab), Genentech’s Avastin, which had $6.9 billion in sales last year. MVASI is the first biosimilar bevacizumab approved by the EC for the treatment of certain types of cancers. Additionally, in September, MVASI became the first anti-cancer biosimilar, as well as the first biosimilar Avastin to be approved by the FDA.

Amgen is currently developing three additional biosimilars with Allergan, ABP 494 a biosimilar to Lilly’s Erbitux, ABP 798, a biosimilar to Biogen’s Rituxan, and Kanjinti, a biosimilar to Genentech’s Herceptin, as well as two others. ABP 710 is a biosimilar to J&J’s top seller Remicade, and ABP 959 aims to compete with Alexion’s flagship rare disease leader, Soliris for Paroxysmal Nocturnal Hemoglobinuria and Atypical Hemolytic Uremic Syndrome.

In other biosimilar news, Amgen and Simcere Pharmaceutical Group are co-developing four biosimilars in China in the areas of inflammation and oncology—all are from Amgen’s existing biosimilars portfolio.

Also, Amgen reached a global settlement with AbbVie to resolve all pending litigation regarding Amgevita, a biosimilar to AbbVie’s Humira. AbbVie will grant patent licenses for the use and sale of Amgevita/Amjevita worldwide, on a country-by-country basis. Amgen expects to launch Amgevita in Europe in October 2018, and Amjevita in the U.S. in January 2023.

Headcount: 20,000
Revenues: $22,991 (+6%)
Net Income: $7,722 (+11%)
R&D: $3,840 (-6%)

TOP SELLING DRUGS  

After nearly 40 years, Amgen remains among the world’s largest biopharma companies with a market cap of $114 billion. In 2016, Amgen’s portfolio of top sellers boasted seven blockbuster drugs (classified as $1 billion or more in annual sales). Of these, five are still growing, Enbrel, Aranesp, Prolia, Sensipar and Xgeva. Osteoporosis drug Prolia, has shown the strongest gains (25%) over the last year. However, biosimilar competition in today’s market is fierce and Amgen’s products are among the prime targets.

Enbrel sales soared 11% in 2016, just shy of $6 billion, while sales of Neulasta, a treatment for chemotherapy induced neutropenia, were pretty much flat at $4.6 billion due to increased competition in this space and patent expirations. Sales of Amgen’s original flagship blockbusters, Epogen and Neupogen (the industry’s first victim of biosimilar competition), have fallen dramatically in recent years, down a third since 2014.

Kyprolis, Blincyto and Repatha are Amgen’s fastest growing drugs but they have a way to go to compensate for the decline of core products.

Despite increased competition and patent expirations, 10 out of Amgen’s 13 products grew in 2016. Not unlike many of its competitors, advancing its pipeline assets is essential to maintaining growth. Amgevita and Erenumab look to be the most promising sources of revenue for the company in the near term.

Safety issues surrounding Evenity and less than impressive Repatha results are among the company’s most recent road blocks. Osteoporosis drug Evenity was close to gaining FDA approval, but a recent study showed an increased risk of heart-related side effects. It’s not likely to be approved this year and its future is in question. Also, Repatha, a new cholesterol reducing drug, showed positive results in a recent study but not enough to impress investors or outstrip the competition, and as a result, it could face tougher payer reimbursement.

In the way of positive news, Amgen submitted a Biologics License Application to the FDA for its new migraine drug Erenumab, which demonstrated positive Phase III results from pivotal studies in more than 2,600 patients with episodic and chronic migraine.

Amgen and development partner, Novartis, recently expanded their collaboration for erenumab, a fully human monoclonal antibody specifically designed to target and block the Calcitonin Gene-Related Peptide (CGRP) receptor, believed to have a critical role in mediating migraine pain. The companies have agreed to combine capabilities to co-commercialize erenumab in the U.S. Amgen retains exclusive rights in Japan and Novartis gains exclusive rights in Canada, retaining its existing rights in rest of the world.

Amgevita, Amgen’s biosimilar to AbbVie’s $16 billion top-seller Humira, was approved by the FDA and the EU, but ongoing litigation could significantly delay launch. Amjevita is the first Humira biosimilar to be approved in the U.S.

AbbVie filed a lawsuit seeking to block Amgen from selling a copy of the arthritis medicine, and according to AbbVie, Amgen’s proposed biosimilar would infringe at least 10 patents, and AbbVie has reserved the right to assert as many as 51 other patents. Unfortunately for Amgen, the trial is not expected to begin until November 2019, and Amgen is not alone in its pursuit for a Humira biosimilar. Samsung Bioepsis’ Imraldi was recently recommended for approval by the EMA. The EMA also recently accepted an application for review from Sandoz, and Boehringer Ingelheim’s recent Phase III study confirmed its biosimilar candidate has similar efficacy, safety and immunogenicity to Humira—just to name a few…

Moreover, with respect to the Sandoz v. Amgen dispute, on June 12, the U.S. Supreme Court released a highly anticipated decision relating to patent disputes between the developers of new biologics and the manufacturers of “biosimilar” copies.

Sandoz received approval from the European Commission for Erelzi, its biosimilar to Amgen’s Enbrel to treat inflammatory diseases such as rheumatoid arthritis, psoriasis, and psoriatic arthritis.

On one issue, Sandoz won. As a result of the court’s ruling, biosimilar companies will generally be able to launch their products as soon as the data exclusivity on the innovative product expires. On the second issue, however, the outcome was a bit murky. Amgen lost the immediate dispute presented to the Supreme Court, but the litigation is not over, and there are still key questions to be resolved concerning not only federal but also state law, namely California.

With respect to innovation efforts, two early stage R&D investments aim to target cancer. Amgen and Immatics Biotechnologies entered a research collaboration and exclusive license agreement to develop next-gen T-cell engaging bispecific immunotherapies targeting multiple cancers. Amgen paid $30 million upfront and Immatics is eligible to receive more than $500 million in development, regulatory and commercial milestones, as well as royalties on sales.

Additionally, Amgen acquired global rights from Boehringer Ingelheim for BI 836908 (AMG 420), a bispecific T cell engager (BiTE) that targets B-cell maturation antigen, a potential target for multiple myeloma. The drug is currently in Phase I studies. The companies will work together on clinical development, transfer of manufacturing, and global regulatory activity.

Among assets closer to fruition, Amgen will sponsor a clinical trial collaboration and supply agreement with Janssen Biotech that will evaluate the efficacy and safety of CD38-directed immunotherapy Darzalex, in combination with Amgen’s proteasome inhibitor Kyprolis and dexamethasone, to treat cancer. The first Phase III study will determine if this combination improves survival compared to Kyprolis and dexamethasone alone in multiple myeloma in patients who have received prior therapies.

Also, Amgen and Daiichi Sankyo Co. entered an exclusive agreement to commercialize nine biosimilars in Japan. The deal includes several biosimilars in late-stage development, including biosimilars of Humira, Avastin and Herceptin. Amgen is responsible for the development and manufacturing of the biosimilars and Daiichi Sankyo will file for marketing approval and be responsible for distribution and commercialization in Japan.

Despite current challenges, Amgen’s strong foundation as a biologics pioneer should prevail. Near term assets and strong revenue streams for top sellers should offset any losses for flagship products—for now.

Headcount: 17,900
Revenues: $21,662 (+8%)
Net Income: $6,939 (+35%)
R&D: $3,917 (-5%)

TOP SELLING DRUGS  

Holding steady at 11 once again this year, Amgen, the grandfather of biopharma, is certainly consistent and key drug approvals for Kyrpolis in multiple myeloma and cholesterol drug Repatha, as well as Imlygic in metastatic melanoma, may help offset some patent losses for key products in the next few years.

Amgen is off to a good start this year. Revenues were up 10% in the first quarter to $5.5 billion, with 7% product sales growth driven by Enbrel (+24%), Prolia (+29%), Aranesp (+11%), Neulasta (+4%), Kyprolis (+43%) and XGEVA (+11%). Earnings were up 17% to $1.9 billion. Overall, Amgen had nine drugs that saw double-digit percentage growth in 1Q16. However, sales of Neupogen were down 13% impacted by the launch of Sandoz’s biosimilar Zarxio in the U.S.

The company is challenged with patent expirations for several significant drugs. Biosimilar rivals for Neupogen and Epogen are beginning to hurt sales, and Neulasta will soon face the same fate. Enbrel could also face biosimilar competition soon. Sandoz’s biosimilar version of Enbrel is expected to come up before the FDA’s Arthritis Advisory Committee next month. The 10-month review process could mean approval by mid 2016, although a launch will depend on the outcome of patent litigation between the two companies. The original patent on Enbrel was set to expire October 2012, but Amgen says it’s protected from biosimilar competition until 2029.

Amgen is pursuing the biosimilar market as well with nine biosimilar candidates representing potential annual revenues of more than $3 billion. The company plans to launch its first biosimilar in 2017, and subject to approval, four others through 2019.

The FDA’s Arthritis Advisory Committee will review data supporting the company’s biologics license application for ABP 501, a biosimilar version of AbbVie’s best-selling drug, Humira, and a final decision regarding approval is expected by September 25th. It’s also under review in the EU. Humira, used to treat rheumatoid arthritis and a number of other inflammatory diseases, had sales of $14 billion in 2015 and is among the top-selling drug products in the U.S.

Nevertheless, innovative pipeline advances are key to sustaining Amgen’s long-term strength. Kyprolis, approved for relapsed multiple myeloma, also got a positive CHMP opinion for expanding the label to include treatment in combination with dexamethasone for patients with multiple myeloma who have received at least one prior therapy. Kyprolis’ label was expanded in the U.S. earlier this year for this indication and is well-positioned to gain market share.

Recent analyses from Phase III studies of Kyprolis, a product of Amgen’s subsidiary Onyx Pharmaceuticals, showed patients with relapsed multiple myeloma live longer without disease progression. Additional analysis based on a head-to-head trial showed Kyprolis with Lenalidomide and Dexamethasone offers substantial value over previous standard of care, and that Kyprolis and Dexamethasone doubled progression-free survival versus Takeda’s Velcade (Bortezomib) and Dexamethasone.

Also, Repatha was approved last August for the treatment of persistently high LDL cholesterol. Studies showed that patients experienced approximately 65% reduction in LDL-C from baseline to end of study.

As far as cholesterol drugs go, Repatha and Sanofi/Regeneron’s Praluent are considered breakthrough therapies for hard-to-treat patients and are the first highly effective cholesterol-lowering medications in a generation. Repatha’s cost is $14,100 per year but as the companies are battling it out to gain payer reimbursements, discounts and deals are unfolding. For example, in the U.S. Express Scripts agreed to offer both Praluent and Repatha on its formulary in exchange for discounts, while Praluent will be UnitedHealth Group’s “preferred” drug for treating high LDL cholesterol and Amgen won a formulary exclusive with CVS.

Lastly, Imlygic, approved for melanoma, has become the first oncolytic viral therapy approved by the FDA based on therapeutic benefit. Imlygic is derived from a herpes simplex virus that has been genetically engineered to infect cancer cells and cause cell death. While the drug has not been shown to improve overall survival, its unique approach provides another option for treating this complex disease that often requires the use of several therapeutic modalities.

Amgen anticipates the average cost of this novel, first-in-class oncolytic viral therapy to be approximately $65,000 and expects variability of IMLYGIC dosing from patient to patient.

Amgen also has collaborations to study the use of Imlygic in combination with two PD-1 inhibitors, Merck’s Keytruda (pembrolizumab) and Roche’s atezolizumab (MPDL3280A). With Merck, the combination is being tested in Phase I open-label trials in melanoma and head and neck cancer, and in a Phase III randomized trial in melanoma. The Roche collaboration is studying Imlygic with atezolizumab in a Phase I study in triple-negative breast cancer and metastatic colorectal cancer. Data indicate that combining the two modalities has a synergistic effect, and the combination has a better side effect profile than the combination of two checkpoint inhibitors.

Imlygic joined Amgen’s portfolio with the January 2011 acquisition of Biovex Group, a privately held, venture-funded, biopharma company headquartered in Woburn, MA, in a deal worth as much as $1 billion, of which $475 million was paid up front, with additional payments of $575 million based on certain regulatory and sales milestones.

Considering the highly lucrative biosimilars market, competition is certainly intensifying. If Amgen can hold off Enbrel competition, it stands to recoup some losses with its late stage biosimilar assets, as well as advance the twelve Phase III clinical studies currently underway.

Headcount: 18,000
Revenues: $20,063 (+7%)
Net Income: $5,158 (+2%)
R&D: $4,121 (+5%)

TOP SELLING DRUGS

neutropenia$5,755-1%Enbrelrheumatoid arthritis$4,6883%XGEVA/Proliabone cancer$2,25128%Epogenanemia$2,0314%Aranespchemotherapy induced

anemia$1,9301%Sensipar/Mimpararenal disease$1,1586%Vectibixcolorectal cancer$50530%Nplateimmune thromboytopenia$46910%Kyprolismultiple myeloma$331n/a

Biotech pioneer Amgen grew its revenue 7% in 2014, crossing the $20 billion threshold for the first time ever. Total product sales increased 6% driven primarily by Enbrel (+3%), Neulasta (+5%), Prolia (+38%), Xgeva (+20%) and Vectibix (+30%). Neupogen (filgrastim) sales declined 17% because the company said an unfavorable comparison to 2013, when the U.S. government put in a $155 million order.

Amgen released Phase III data evaluating efficacy and safety of biosimilar candidate ABP 501 compared with Humira (adalimumab) in patients with moderate-to-severe plaque psoriasis. The primary endpoint was the Psoriasis Area and Severity Index (PASI) percent improvement from baseline to week 16 of treatment. At week 16, the PASI percent improvement from baseline was within the pre-specified equivalence margin for ABP 501 compared to adalimumab. Safety and immunogenicity of ABP 501 were comparable to adalimumab. This is the first of two Phase III studies intended to form the basis for global regulatory submissions for ABP 501. Amgen also expects Phase III data for biosimilar candidate ABP 215 (bevacizumab) in patients with advanced non-small cell lung cancer in the second half of 2015.

Amgen received FDA approval for its bispecific T-cell engager (BiTE) immunotheraphy Blincyto (blinatumomab) for the treatment of a type of acute lymphoblastic leukemia (ALL). With this approval, Blincyto becomes the first FDA-approved bispecific CD19-directed CD3 T-cell engager (BiTE) antibody construct product, and the first single-agent immunotherapy to be approved for the treatment of patients with Ph- relapsed or refractory B-cell precursor ALL, a rare and rapidly progressing cancer of the blood and bone marrow.

Amgen and Kite Pharma entered into a strategic research collaboration and license agreement to develop and commercialize the next generation of novel Chimeric Antigen Receptor (CAR) T cell immunotherapies based on Kite’s engineered autologous cell therapy (eACT) platform and Amgen’s cancer targets.

Amgen will contribute cancer targets and Kite will use its CAR platform, R&D and manufacturing capabilities to conduct preclinical research, cell manufacturing and processing through Investigational New Drug (IND) filing. Each company will then be responsible for clinical development and commercialization of their respective CAR therapeutic candidates.

Kite will receive an upfront payment of $60 million, R&D funding, and is eligible to receive as much as $525 million in milestones per Amgen program, as well as royalties on sales and the license of Kite’s intellectual property for CAR T cell products. Amgen is eligible to receive as much as $525 million in milestones per Kite program, plus royalties.

Massachusetts General Hospital (MGH), the Broad Institute, and Amgen launched a strategic collaboration to jointly discover and validate new therapeutic targets and develop novel therapies for inflammatory bowel disease (IBD), a chronic disorder that affects millions worldwide. The MGH-Broad-Amgen collaboration brings together scientists with expertise in clinical medicine, IBD biology, human genetics, genomic technology, and drug discovery to work together to help create a new world of therapeutic options for IBD patients.

During the year Amgen also has completed its first next-gen biomanufacturing facility in Singapore encompassing multiple technologies aimed at enabling greater speed, productivity and flexibility in commercial-scale manufacturing.

The new Taus facility uses single-use bioreactors, disposable plastic containers, continuous purification processing and real-time quality analysis, and, according to the company, was completed in half the time required for conventional biomanufacturing plants. This flexible, modular design can be replicated in future facilities, enabling higher production and greater accessibility to patients globally.

The facility is expected to have the same annual output as a conventional facility but in a single building that will use fewer resources. The company also plans to build another facility at its Tuas site in Singapore to make carfilzomib, the active ingredient for Kyprolis.

Amgen seems to be in a stage of transition with its portfolio. Bearing in mind it comes with a history of biotechnology, the company really only has two block- buster products, which make up more than 50% of its revenues. In recent years, the company has made advances in cancer immunotherapy and this may be where Amgen sees its future.

The company recently announced collaborations with Roche in investigational oncolytic immunotherapy, and this past spring, Amgen made an announcement about expanded investigations with Merck on combination therapy with Keytruda. Amgen also received recommendation for approval in the EU for Repatha (evolocumab), and expects to receive EMA approval in mid-summer for this cholesterol lowering ‘blockbuster in the making’.

However, Amgen has a challenging time ahead with Epogen having had a patent expiration in May in the U.S. and Neulasta set to come off patent in October. This product has netted $3.7 billion in the U.S., so we aren’t just talking pocket money. With biosimilars already knocking on the door, Amgen is going to have to come up with an ingenious idea—and may well do so by developing its own biosimilars. If you can’t beat them join them!

The company aims to have its first to market by 2017 and there may be three or four more in the next few years. But with a statement of restructuring in 2015, and redundancies ahead, on top of no definite replacement for its current money makers, it will be interesting to see how they negotiate the rocky road.

—Adele Graham-King

Headcount: 20,000
Pharma Revenues: $18,676 (8%)
Net Income: $5,0811 (7%)
R&D Budget: $4,0832 (4%)

Top Selling Drugs 

It is hard to say the word biotechnology without thinking of Amgen, the iconic California company which started up in 1980 and, using roller bottle technology, commercialized the first recombinant product, Epogen, for anemia treatment, nine years later.
The company recently hired a new CFO, David Meline, formerly with 3M, and has been strengthening its cancer drug pipeline, acquiring Onyx Pharma last October, investing $9.7 billion, to help it in this area.

Most recently, Amgen has had some significant breakthroughs in cancer immunotherapy. Some of them were discussed at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago. An example is talimogene laherparepvec, a treatment for metastatic melanoma that has been found to be potentially useful both as a single treatment and as part of a combination therapy.

In early Phase Ib combination studies with ipilimumab, talimogene led to tumor shrinkage or removal in 56% of patients administered the drug.

“We are entering an era where new melanoma therapies are advancing clinical care for patients in ways not previously seen,” said Sean E. Harper, M.D., Amgen’s executive vice president of Research and Development. “Talimogene laherparepvec has demonstrated the ability to produce durable and complete responses in patients with metastatic melanoma, which provides a strong basis for a filing later this year and potential approval as a novel treatment.”

Among patients who saw an overall response in Phase III studies, 40% showed complete response (i.e. no evidence of disease) after treatment, and, the company reported, among those who responded positively to the drug, there was a 65% probability of those responses lasting for at least a year. In Phase III trials of the drug, used alone, those who responded showed a 4.4-month improvement in overall survival.

“Novel investigational therapies are creating exciting momentum in melanoma research and our challenge is to better understand how to most appropriately develop these therapies,” said Igor Puzanov, M.D., associate professor of Medicine at Vanderbilt-Ingram Cancer Center and lead author on the Phase 1b combination study. “These latest findings support the potential of talimogene laherparepvec as a single agent and provide a strong rationale for further investigation as a combination therapy in a broad range of appropriate patients.”

At ASCO, Amgen also presented results from Phase II tests that reinforced the improved overall survival benefit of panitumumab (Vectibix) when used in combination with FOLFOX, an oxaliplatin-based chemotherapy regimen, compared to bevacizumab (Avastin) plus FOLFOX as first-line treatment in patients with wild-type RAS metastatic colorectal cancer (mCRC).

Patients who received panitumumab plus FOLFOX and were then treated with a VEGF inhibitor-based treatment (including bevacizumab) had a median OS improvement of 41.3 months. By comparison, those who were given bevacizumab plus FOLFOX and were then treated with an anti-EGFR inhibitor-based treatment (including panitumumab/cetuximab), had a median OS improvement of 29.0 months.

Recently, FDA granted Breakthrough Therapy Designation to Amgen’s investigational bispecific T cell engager (BiTE) antibody blinatumomab, for adults with Philadelphia-negative (Ph-) relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL), a rapidly progressing cancer of the blood and bone marrow.

The Breakthrough Therapy Designation was based on the results of a Phase II trial of 189 adult patients with Ph-relapsed/refractory B-precursor ALL treated with blinatumomab. Data from the Phase II trial were most recently presented at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO) and the 19th Congress of the European Hematology Association (EHA).

Using Biomarkers to Fight Lung Cancer
Amgen will collaborate with the National Cancer Institute (NCI), part of the National Institutes of Health, and other public and private sector partners on the Lung Master Protocol (Lung-MAP), a new clinical trial program that will use biomarker-driven research and genomic profiling to match squamous cell lung cancer patients to investigational treatments based on their individual cancer profiles. Lung-MAP is the first trial of its kind to study a large number of rare lung cancer subsets under one trial protocol.

Approximately 500 to 1,000 patients will be screened each year for more than 200 cancer-related genes, and the screenings will inform trial arm selection. Five investigational drugs have been selected for inclusion in the initial trial, including Amgen’s rilotumumab.

Headcount: 18,000
Bio/Pharma Revenues: $16,639 (9%)
Total Revenues: $17,265 (11%)
Net Income: $4,345 (18%)
R&D Budget: $3,380 (7%)

Top Selling Drugs

Account for 99% of total biopharma sales, down from 100% in 2011

Amgen has been stuck on five blockbusters for years — Enbrel, and its EPO and Filgrastim franchises — but it looks like it’s about to break out of that rut in a big way. Sensipar narrowly missed the billion-dollar milestone in 2012, while XGEVA and Prolia are each rocketing towards that mark and continue to expand their labels. (They’re the same biologic, but serve different indications.)

Amgen’s co-promotion pact with Pfizer (previously Wyeth) for Enbrel in the U.S. and Canada will expire in July 2013, giving Amgen more freedom to promote Enbrel, along with reduced royalty payments (10-12% of sales) to Pfizer until their overall Enbrel deal expires in 2016. That may not boost Enbrel sales for Amgen, but it sure will increase earnings; Amgen paid out $1.5 billion to Pfizer in 2012 as part of the pact, so a 12% royalty would have amounted to $1.0 billion in earnings.

The company plans to “deliver” at least $800 million to shareholders in 2014 from that transition, while also earmarking $1.0 billion in the next three years toward “strategic initiatives.” Amgen could have used that Enbrel money to pay the $762 million settlement it reached with the feds, states and D.C. in December 2012 over improper marketing of all of its major drugs. The settlement includes a $150 million criminal liability over Aranesp marketing.

It’s critical for Amgen to find new revenues, since several of its established biologics are finally facing generic competition. The patent protection for Neupogen expires in December 2013, while Neulasta will lose protection three years later. Tevagrastim, a competitor developed by Teva with a full BLA (that is, not along a biosimilar pathway), will launch in November 2013, as per an agreement between the two companies.

Amgen dodged another not-quite-biosimilar bullet as Affymax/Takeda’s Epogen-killer Omontys turned out to be a patient-killer. The drug was pulled from the market in February 2013 after a small percentage of dialysis patients had severe anaphylactic reactions. Previously, Amgen had been pilloried for locking up dialysis centers with incentives to continue using Epogen over the new drug. In hind-sight, Amgen’s market machinations may have saved patients’ lives.

Omontys was a functional PEGylated analog of erythropoietin, a chemical workaround for Epogen rather than a biosimilar, but the dramatic adverse effects on patients comprise a stark reminder of how careful drug companies and regulatory bodies will have to be when they consider biosimilars.

Amgen has been trying to lead legislation in individual states to block substitution of biosimilars by pharmacists, citing safety risks. At the same time, the company hopes to enter that market by 2017 and has six biosimilars in development, targeting AbbVie, Remicade, Avastin, Herceptin, Rituxan and Erbitux. Those six drugs had $41 billion in 2012 sales. It looks like Amgen will be agin’ it until it’s fer it. (We know it’s not that simple; the argument is that companies with more experience in developing branded biologics will fare better in developing biosimilars that don’t kill patients.)

At a pipeline event in February 2013, Amgen’s new R&D team noted that the copany now “embraces a ‘pick the
winners’ approach.” The biggest prospect in Amgen’s pipeline remains AMG-145, a biologic treatment for high cholesterol. In November 2012, the company released results from several Phase II studies showing impressive results in lowering LDL cholesterol. The drug is intended for patients who can’t take statins or don’t see enough results from statin treatment. Amgen is planning to conduct seven Phase III trials with 26,000 patients, with results expected by 2014, as well as an outcomes trial of 22,500 patients that should have results in 2018. Amgen’s in a race with Sanofi and Regeneron’s SAR236553/REGN727, which is already in Phase III.

In addition to developing new blockbusters, Amgen’s also trying to build its presence in new markets. At its pipeline meeting, the company put forth the goal of reaching $1.0 billion in sales in new and emerging markets by 2015. The company plans to launch its first products in China by that year.

In May 2013, the company formed a joint venture with Astellas to build an alliance in Japan. Amgen and Astellas will collaborate on five Amgen pipeline molecules in the Japanese market and also form a Tokyo-based company that will begin operations in October 2013, with the goal of giving Amgen a stand-alone subsidiary there by 2020. Terms of the deal weren’t disclosed.

Amgen has a good chance of holding on to the #2 position in our Top Biopharma ranks, even after AbbVie moves over next year. After that, it’ll be a question of whether Enbrel and XGEVA/Prolia’s growth can outstrip the erosion to Neupogen/Neulasta.

Lowe Down
Amgen’s got a lot on its plate. It’s trying to expand the markets for recent drugs, even though nothing looks like it’ll be as big as their older ones, or not for a while yet. And Novartis (in the form of Sandoz) is coming after top drug Enbrel with a biosimilar.

But the old stuff is still selling, and at the same time, there are some key late-stage drugs in trials. These are legacies of the era of Roger Perlmutter, now taking names and shaking his head over org charts at Merck. And biosimilars? The company says that it’s hoping to launch six of then in 2017, which would make for quite a year (both for Amgen and for the people at the FDA who will have to evaluate all of them).

These factors, pointing in all directions at once, let you imagine whatever future you please for Amgen — just mix and match the drugs, their successes or failures, and the timing thereof. You can get pretty much any number you like (and a lot you won’t like). At the moment, this is not only a biotech company, it’s a Rorschach blot. Look into its pipeline and look into your own heart!

—Derek Lowe

Acquisition News
Target: deCODE Genetics
Price: $415 million
Announced: December 2012
What they said: “[deCODE’s capability  in the study of the genetics of human disease] will enhance our efforts to identify and validate human disease targets. This fits perfectly with our objective to pursue rapid development of relevant molecules that reach the right disease targets while avoiding investments in programs based on less well-validated targets.”

—Robert A. Bradway, president and chief executive officer, Amgen.

Headcount: 17,000
Biopharma Revenues: $14,687 (+3%)
Royalty Revenues: $316 (+4%)
Total Revenues: $15,003 (+2%)
Net Income: $4,196 (+33%)
R&D Budget: $3,003 (-7%)

Account for 98% of total pharma sales, same as in 2007.

PROFILE

We launched this report in 2001, and in all the years since, I never thought, “Boy, I wonder if Amgen is going to get acquired.” But the premiere biopharma company has cropped up in several buyout rumors in the past year, most recently as the unnamed “U.S. drug company” that Sanofi-Aventis steadfastly denies it’s interested in acquiring.

Until recently, it was unthinkable that Amgen would be in play, so how did a #1 company end up in this position? The hard way! For years, Amgen has relied on five key products for virtually all of its revenue. With no significant additions to its lineup after the Enbrel (which it gained by acquiring co-marketer Immunex in 2002), Amgen’s reliable growth engines left the company vulnerable.

Label restrictions and warnings for its top seller, Aranesp, trimmed $1.0 billion in sales from 2006 to 2008. In 1Q09, sales dropped another 18%, to $626 million, with U.S. sales plummeting 28%. Same story for Epogen, which is also staring at competition from several biogenerics. Enbrel, meanwhile, faces heavy competition from other TNF-alpha inhibitors and the next generation of autoimmune treatments (see “FOB Off” for more). That means 60% of Amgen’s revenues are under siege.

At $597 million in 2008 sales, Sensipar is the only Amgen product to break out of the dreaded “Other” category, a group that contributed only $240 in sales for Amgen last year.

Mr. Wonderful and the Others

In August 2008, Amgen added to the “Others” when the FDA approved Nplate, its weirdly named treatment for immune thrombocytopenic purpura (ITP). It’s not regarded as a future blockbuster (sales estimates peak around $500 million), but at least Amgen was able to develop it and reach the market before GSK’s competitor, Promacta. The EU approved Nplate earlier this year.

One analyst pointed out that Amgen’s done a great job of treating the side effects of cancer treatment, but hasn’t developed muchto treat cancer itself. That’s easier said than done, of course. Amgen did manage to get colorectal cancer treatment Vectibix on the market in 2006, but that was a lengthy process and the drug, an anti-EGFR MAb a la Erbitux, is struggling to gain a foothold in the market. Amgen hopes to get broader approval for the treatment, and has a pair of major studies going on to establish the benefits of Vectibix with chemotherapy to treat metastatic colorectal cancer. Results from those trials should be available in 3Q09. The company’s also trying out Vectibix against head and neck cancer. If it proves effective in those situations, Vectibix could become a billion-dollar drug for Amgen within a few years.

With partner Takeda, Amgen is also conducting lung cancer trials on on motesanib, a small molecule anti-VEGF treatment. The companies had to suspend part of a trial against non-small cell lung cancer in November 2008 because of higher deaths in one subgroup of patients. After a three-month hiatus, the trial’s independent data monitoring committee approved resumption of the trial, excluding that subgroup.

Prolia Good Idea

But really, what’s it going to take for Amgen to remain an independent company? One word: denosumab.

Ostensibly a treatment for osteoporosis, denosumab (tentatively named Prolia) may also be Amgen’s trojan horse. Submitted to the FDA in December 2008, denosumab’s BLA is for treatment and prevention of postmenopausal osteoporosis, and treatment and prevention of bone loss in patients undergoing hormone ablation for either prostate or breast cancer. While it has a novel method of action, osteoporosis treatment is a crowded field. With Merck’s Fosamax going generic, denosumab would have to show tremendous results to warrant its expense. In the area of preventing bone loss in cancer patients, denosumab could be in competition with Novartis’ Zometa.

Ah, but what if denosumab also turns out to have oncology benefits? That would be a game-changer for our beleaguered biopharma. The drug is currently being studied in the prevention of bone metastases in prostate cancer, an indication for which there is no other available treatment. Results of the study — which are part of a mega-trial of denosumab — are expected to come out by September.

If the drug proves beneficial in blocking bone cancer in prostate and breast cancer cases, then Amgen is going to be sitting pretty. Some analysts project its potential revenues in those two cancer indications to be as high as $3.0 billion a year. (And I’m sure the osteoporosis indication would at least have better revenues than the “Other” category.)

The FDA has scheduled an August 2009 meeting of its reproductive health drugs advisory committee to discuss denosumab’s initial BLA, with a PDUFA action date (ha-ha) of October 2009.

Out-License To Print Money?

A denosumab launch is going to cost plenty as the company ramps up sales and marketing and continues major trials. To conserve cash Amgen finished up the first major restructuring in its history last year, incurring around $900 million in downsizing charges from 2007 to 2008. Along with the cost-cutting, Amgen is continuing its efforts to monetize its pipeline through out-licensing. In last year’s edition, we documented the extensive development and commercialization deals Amgen signed with Takeda in February 2008, providing Takeda with rights in the Japanese market to 13 early-stage molecules.

The company continued the practice in July 2008, when it licensed one of those molecules, a potential treatment for chronic and neuropathic pain, to Ortho-McNeil-Janssen, a J&J unit. Amgen received $50 million upfront, with a potential for as much as $385 million in development milestones and subsequent royalties and sales bonuses.

In September 2008, Amgen sold off rights to its drugs Kepivance and Stemgen to Biovitrum, which also bought an exclusive worldwide license to Kineret for its approved indication. Biovitrum paid $110 million in cash and $20 million in shares, and the agreement includes sales milestones for Amgen and possible royalties if Biovitrum develops modified forms of Kineret. The three drugs added up to $70 million in 2008 sales. Announcing the deal, Mr. Sharer remarked, “This deal will allow Amgen to focus its resources on developing new, innovative therapies for serious illnesses, and on expanding its core products to benefit more patients in markets around the world.”

Moves like this show an Amgen that understands that even the biggest biopharma doesn’t have the resources to do everything. But it needs to do a couple of things very well in the near future if it wants to stay Amgen.

Headcount: 17,000
Pharma Revenues: $14,660 (2%)
Total Revenues: $15,053 (3%)
Net Income: $4,627 (0%)
R&D Budget: $2,894  (1%)

Top-Selling Drugs in 2010

Account for 98% of total biopharma sales, down from 99% in 2009.

PROFILE

I turned 40 this year, a milestone that removes all notion that I’m not middle-aged. Similarly, Amgen crossed a threshold in which it admitted to itself and the public that it’s no longer a high-flying growth company. Four years of stagnant sales — equivalent to my sore back and inability to run more than 30 yards without wheezing — has led Amgen to admit to itself that it’s a mature company. Amgen announced in April 2011 that it will pay out its first dividend, responding to investor concerns that the company was piling up too much cash with no goal for it. (And perhaps pre-empting an attack by activist investor Carl Icahn, who began buying up Amgen shares in early 2011.)

The move was Amgen’s admission that a major acquisition wasn’t as worthwhile to shareholders as a cash return. The company also initiated a $5.0 billion stock buyback, hoping to placate shareholders who have grown impatient with the company’s slowing growth. The dividend and buyback also allay fears that Amgen would make a sizable, difficult-to-integrate acquisition in order to goose revenues. Rumors had been swirling that Amgen was looking to buy Swiss biopharma Actelion, to get hold of its pulmonary arterial hypertension pipeline. Estimates for that acquisition soared as high as $10.0 billion.

This isn’t to say that Amgen doesn’t have its own growth prospects. Denosumab — marketed as Prolia for osteoporosis and Xgeva for prevention of bone metastases in cancer — is hugely important to Amgen’s future. Estimates for peak sales have been all over the place, ranging from $1.0 billion to a Lipitor-sized $10.0 billion in annual revenues. Amgen itself projects denosumab will sell bring in $3 billion to $4 billion by 2015, as reimbursement expands, new indications are approved, and more clinical data gets generated.

However, the new biologic started off small, posting a mere $10 million in sales in 3Q10, its first full quarter on the market. It brought in a combined $69 million for Amgen in 1Q11: $27 million for Prolia, $42 million for Xgeva.

Uptake can’t come quickly enough. Amgen posted its first revenue decline in 2009, followed up by an anemic (ha-ha) 2% rise in 2010. Revenues rose 3% in 1Q11, but Aranesp, Epogen and Neupogen, three of Amgen’s mainstays, posted revenue drops of 7%, 14% and 6% during the quarter, respectively. Neupogen has faced biosimilar competition abroad, and Amgen has also worked to move patients from that drug over to Neulasta, which passed Enbrel to become Amgen’s top seller in 2010. (Expect those two to go neck-and-neck for the top honors this year, despite the competition that has slowed Enbrel’s growth.) Sensipar, Vectibix and Nplate — the company’s first wave of new drugs to follow the Epogen/Neupogen/Enbrel wave — are showing signs of success, albeit in the sub-$1.0-billion range.

With a not-ready-for-prime-time late-stage pipeline — Amgen has a number of drugs in Phase III, but none on the verge of filing BLAs/NDAs — the next few years will focus on denosumab’s success and the company’s ability to expand into new markets and streamline operations. The company plans to boost its presence in emerging regions, including Russia, Turkey, Mexico and Brazil (see Acquisition News for more on its play in Brazil), and hopes to pass $1.0 billion in annual sales from new and emerging markets by 2015.

In January 2011, Amgen announced that it was selling its biomanufacturing facility in Fremont, CA to Boehringer Ingelheim, which will use it for contract manufacturing. The site was part of Amgen’s 2006 acquisition of Abgenix, and BI will continue to make Vectibix in Fremont through the end of 2012. In June 2011, Amgen announced 134 layoffs at its Longmont and Boulder manufacturing sites in Colorado. Longmont performed bulk manufacture of Aranesp and Epogen. Around 700 staffers will remain at the two sites.

It’s not all divestitures and belt-tightening at Amgen. Back in 2006, the company had been planning a billion-dollar expansion in County Cork, Ireland, but the aforementioned business slowdown led to those plans getting scuttled. Now Amgen is buying into Ireland by acquiring a Pfizer facility. In March 2011, Amgen announced that it will buy Pfizer’s 37,000-sq.-m. facility in Dun Laoghaire, Dublin. The site employs 280 people, all but 40 of whom will transfer to Amgen. The remaining staffers will be Pfizer employees.

As noted in our interview with Pfizer’s John Kelly elsewhere in this issue, the Dublin site includes a trailing supply agreement (terms not disclosed), keeping the site busy with Pfizer products while Amgen prepares it for its next stage of internal sterile fill/finish production. The site has been in operation since 1970.

If denosumab can hit escape velocity quickly enough, Amgen may be able to weather the storm of EPO restrictions, biosimilar competition, and reimbursement issues that have slowed the company to a crawl.  —GYR

THE LOWE DOWN

Well, we can talk about Amgen’s pipeline — the part that’s older, still profitable, but perhaps deteriorating a bit, and the part that’s newer and maybe promising. But let’s talk about Carl Icahn instead. He’s just been buying a stake recently, and he never does that just for laughs.

No, Mr. Icahn buys stuff to turn around and sell it at a higher price. Well, most investors do (you’d hope) but he is actually in a position to do something about the weather. A big Amgen auction would probably go over pretty well, since there had been Icahn-less takeover/merger speculation before. So look for the usual elect-my-buddies-to-your-board tactics, and lots of talk about how the company could be making so, so much more of its assets.

Honestly, whether we — or they — like it or not, I have to think that the days of independent Amgen may already be numbered. So those questions I asked last year about how the company would age, and how it would adapt? Moot points, most likely. We’ll probably never know.  —Derek Lowe

ACQUISITION NEWS

Target: BioVex

Price: $425 million in cash, as much as $575 million in milestones

Announced: January 2011

What they said: “OncoVex has demonstrated encouraging anti-tumor activity in clinical studies for the treatment of melanoma and head and neck cancer, and BioVex is currently enrolling patients into pivotal Phase 3 trials in both indications.”

—Roger M. Perlmutter, M.D., Ph.D.,

Executive Vice President, R&D, Amgen

Target: Bergamo

Price: $215 million

Announced: April 2011

What they said: “Acquiring Bergamo, a profitable company with an established local infrastructure, and regaining the rights to our products in Brazil [Vectibix, Sensipar and NPlate, via a separate transaction with Mantecorp], provides us an attractive entry into the Brazilian market.”

—Kevin Sharer, chairman and

Chief Executive Officer, Amgen

Previous Profile: Roche // Next Profile: Novo Nordisk

Headcount: 17,200
Bio/pharma Revenues: $14,351 (-2%)
Royalty Revenues: $291-8%)
Total Revenues: $14,642 (-2%)
Net Income: $4,605 (+14%)
R&D Budget: $2,864 (-5%)

Account for 98% of total bio/pharma sales, same as in 2008.

PROFILE

I know Amgen isn’t happy about being supplanted as the world’s biggest biopharma company (by our arbitrary standards), but the company is thrilled to have U.S. and EU approval of Prolia (a.k.a. denosumab), its semi-annual postmenopausal osteoporosis treatment. Some analysts project $1 billion in sales in its first full year, and $3 billion in annual sales by 2013, which require a mind-blowingly fast uptake. If you’ve been reading these profiles sequentially, then you know that we may not be in an era of rapid mega-blockbusters anymore. Of course, if Prolia’s oncology benefits pan out, then all bets are off. In the EU, it received the expanded indication to treat bone loss in a subset of men being treated for prostate cancer.

One of the questions analysts had about Prolia was how well Amgen would be able to sell it. Osteoporosis is a different market than anemia and chemotherapy, after all; Prolia is the first biologic in the primary care setting. How would they manage the expense and develop the expertise to build a salesforce in all its markets?

In July 2009, Amgen made its task easier by partnering with GlaxoSmithKline on commercializing Prolia for osteoporosis in Europe, Australia, New Zealand and Mexico. Amgen held onto U.S./Canada rights and also retained oncology sales in Europe and other markets. (Daiichi Sankyo has sales rights in Japan for osteoporosis, oncology and other indications.) GSK paid $120 million in upfront costs and near-term milestones for the deal; the companies will share profits after accounting expenses. GSK will also buy Prolia supplies from Amgen for sale in emerging markets. In January 2010, Amgen also signed a deal to let GSK subsidiary Stiefel promote Enbrel in the U.S. dermatology market.

Prolia’s approval couldn’t come at a better time (well, it could’ve come a year ago, which would’ve helped). After two years of minuscule sales growth, Amgen saw its revenues shrink for the first time, dropping around 2%. For 1Q10, the company posted growth of 9%, with modest growth across the product line, except for Aranesp, which was flat.

Last year’s edition marked the first time Amgen posted a new $500 million or better product since Enbrel, as Sensipar gained nearly 29% in revenues to hit $597 million. Sensipar only added 9% growth last year, but that was the largest percentage increase of any Amgen top-seller. Amazingly, the next-best performer was the company’s oldest drug, Epogen, sales of which grew 5% in 2009. The old-timer posted 10% gains in 1Q10, while Sensipar revenues were up 21% as international demand rose.

Epogen’s success isn’t limited to the marketplace. Amgen successfully walloped Roche in court last summer for infringing on Epogen’s patents with its pegylated-erythropoietin drug, Mircera. Amgen reached a settlement with Roche in December 2009, permitting Mircera into the U.S. market in mid-2014. Neither company revealed financial terms or royalties. Presumably, Mircera will have to develop a REMS program similar to the ones Amgen and J&J put in place for their erythropoietin-stimulating agents (ESAs) in February 2010.

I thought Vectibix, a colorectal cancer treatment that competes with Erbitux, would be the next Amgen product to cross that $500 million barrier, after it posted $233 million in 2009 sales. But a closer look at the numbers showed that the drug’s growth has stalled in the U.S., while international revenues are picking up with new market introductions. In April 2010, Amgen announced results of a biomarker study that may help identify cancer patients who will benefit from Vectibix. Here’s hoping that personalized medicine works out.

Once Roche made the move to integrate Genentech, there was no way for Amgen to hold onto the top spot in our ranks. It would’ve had to launch the biopharma equivalent of Thriller to generate enough sales for that. While Amgen seems to have weathered the ESA storm pretty well, and has a number of oncology drugs that are posting strong results in trials, the story for next few years will be Prolia.

Return to Top Biopharma Report homepage.

Headcount: 17,500
Biopharma Revenues:$14,311 (+3%)
Royalty Revenues: $460 (+4%)
Total Revenues: $14,771 (+12%)
Net Income: $3,166 (+7%)
R&D Budget: $3,266 (-3%)

Account for 95% of total pharma sales, down from 97% in 2006.

PROFILE

Last year, I noted that Amgen had turned in its first year of sub-20% revenues growth. I blithely wrote, “I’m just hoping that it doesn’t fall under 10+% in 2007.” Turns out I didn’t know the half of it. Amgen’s drug revenues last year were up an anemic (ha-ha) 3%, actually dropped 2% in 1Q08, and don’t look like they’re going to get better for the rest of this year.

The collapse was triggered by restrictions on Aranesp and Epogen. Safety studies revealed previously unknown risks in erythropoietin stimulating agents (ESAs) last year, leading to “black box” warning labels, reduced Medicare reimbursement, dosage restrictions, and a whole lot of lost sales. The safety issues continue to unfold.

In March 2008, Amgen changed the label for Aranesp and Epogen to explicitly warn doctors against using high doses of the drugs for patients with early-stage breast, non-small cell lung, head and neck, lymphoid and cervical cancers, after studies showed increases in mortality and tumor progression. Not what you want in a drug used by cancer patients.

Aranesp sales plummeted 25% in 1Q08 to $761 million, with a 38% drop in U.S. sales. Epogen revenues dropped 11% $554 million in that span. Those are awful numbers, keying the company’s 2% decline in the quarter, but the new warning label is sure to hammer the company’s revenues further.

Amgen’s ESA issues haven’t been confined to the label. The company has also been involved in a lengthy court battle with Roche over the Swiss company’s ESA drug Mircera, a pegylated-erythropoietin (peg-EPO) product. Roche received FDA approval for the drug, but the U.S. Patent & Trademark Office ruled that Roche’s process infringes on numerous Amgen patents. Negotiations are ongoing, but Amgen seems adamant in not permitting a kindasorta biosimilar on the market, especially if it offers an improvement on dosing cycles.

Phthisis Ridiculous

Did I mention that Amgen’s #2 seller, Enbrel, might be linked to tuberculosis? The drug carried a warning about that topic previously, but a “black box” was added in March 2008 to highlight the risk of TB and other infections in patients. Other drugs in the TNF-alpha inhibitor class carry the same warning, so this wasn’t as horrible a set of circumstances as Amgen’s ESA collapse, but it can’t make the company happy.

Neither can the news that the FDA is looking into whether TNF-blockers may increase the risk of cancer in children. The agency announced it was looking into it in June 2008, the same time that an advisory panel narrowly recommended Enbrel for use in children’s psoriasis.

Enbrel has actually performed pretty well in its tough category (although there are some questions about Amgen’s marketing practices with the drug), and will take over as Amgen’s top seller next year.

Rationalizing

What’s a company to do when it faces this much lost revenue? Restructure! For the first time in its history, Amgen last year began a program of mass layoffs and cost cutting. The initial announcement in August 2007 targeted 2,200 to 2,600 firings, or 12-14% of the company’s total headcount. In addition, the company planned to “rationalize” its manufacturing network, hold off on new capital expenditures, and rethink its R&D plans.

The plan is designed to cut $1.0 to $1.3 billion from Amgen’s expenses by this year. As part of the plan, Amgen revised its expansion in Puerto Rico, delayed construction of a new facility in Ireland indefinitely, closed down bulk Enbrel operations in West Greenwich, RI earlier than planned and shuttered a clinical manufacturing site in Thousand Oaks, CA. Restructuring costs in 2007 added up to $739 million.

The company also reported in its SEC filing that it is implementing an enterprise resource planning system to “support our increasingly complex business and business processes.” I’m not sure if this is a “duh” move for them, similar to Jeff Bezos’ admission that Amazon was still doing its accounting on Quicken when it was approaching $100 million in revenues.

Still Spending

All this restructuring doesn’t mean Amgen’s in a no-spend mode. Shortly before the announcement was made last year, the company made a pair of acquisitions (covered in the 2007 edition of this issue), spending $720 million to pick up Alantos and Ilypsa. The Alantos acquisition gives Amgen entree into the DPP-4 inhibitor arena, which is fraught with regulatory peril (especially now that the FDA is ready to ask for CV risks for any new diabetes treatment) and one dominant player in Merck’s Januvia, but can help the company make headway in the metabolic field.

In March 2008, Amgen made a $520 million deal ($100 million upfront, plus milestones) with Kyowa Hakko Kogyo for a CCR4 inhibitor (think inflammation and oncology) headed toward Phase II. Amgen will have commercialization rights outside of Japan, South Korea, China and Taiwan.

Eastern Promises

Along with cost-cutting measures, Amgen also decided to license out some of its drug programs, bringing in cash and reducing R&D expenses. In February 2008, Amgen signed a deal with Takeda to give allow that Japanese pharma company to develop and commercialize as many as 13 Amgen molecules for the Japanese market. According to an Amgen statement, “the collaboration includes early to mid-stage clinical-stage candidates across a range of therapeutic areas, including oncology, inflammation, and pain.”

It also includes money. Takeda paid Amgen $200 million upfront for the deal, will cover as much as $340 million in development costs, and may pay as much as $362 million in milestones, as well as royalties.

A separate deal allowed Takeda to buy into late-stage cancer treatment motesanib diphosphate. This deal makes Takeda a worldwide partner on the Phase III drug for $100 million upfront, $175 million in milestones for the first two indications, double-digit royalties on sales in Japan, and 60% of ongoing development costs outside Japan. The companies will split profits outside Japan down the middle.

Their partnership also covers Vectibix, the colorectal cancer MAb that Amgen got approved in 2006. It posted sales of $170 million in its first full year, but dropped 33% to $34 million in 1Q08, on lack of demand. The company is engaged in a number of trials to expand the drug’s label, and has also gained several new markets in Canada and Australia for Vectibix.

Good to the Bone?

Much of Amgen’s pipeline hopes are pinned on denosumab, a bio-treatment that will be submitted for postmenopausal osteoporosis, but is also being investigated against a number of indications, including treatment-induced bone loss, bone metastases, rheumatoid arthritis, and multiple myeloma, according to the company.

The drug (no commercial name yet) has been touted as a $2.0 billion+ blockbuster for Amgen, with some estimates reaching $3.3 billion/year, based on strong results against existing treatments. There have been some concerns with rates of infection among clinical trial patients, but Amgen has stressed that these are not out of the norm, based on the trial’s population group. The company plans to have all data in and analyzed by the end of this year, leading to a submission in early 2009.

Amgen isn’t devoid of hope, but the company has a very tough road. There are rumors that a second round of layoffs is pending, with the total goal of dropping the workforce numbers by 20%, not the 12-14% of the original plan. I hope that’s not the case, but this company’s prospects look bleak for the next several years, and that’s assuming denosumab is an instant hit (and that there’s a nice boost from Nplate, a platelet-boosting drug that just got delayed three months by the FDA).

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