Headcount: 18,000
Revenues:   $27,116 (flat)
Net Income: $5,613 (+23%)
R&D Expenses: $5,718 (+15%)

Gilead’s full year 2023 revenue decreased 1% to $27.1 billion compared to 2022, largely driven by a reduction of $1.7 billion in Veklury sales, but offset by higher HIV and Oncology sales. Daniel O’Day, Gilead’s Chairman and Chief Executive Officer, called 2023 “another strong year for Gilead’s base business, driven by both HIV and Oncology.”

Total full year 2023 product sales of $26.9 billion were relatively flat compared to the same period in 2022. Total product sales, excluding Veklury, increased 7% to $24.7 billion in the full year 2023 compared to 2022. The decline in Veklury sales was primarily driven by lower rates of COVID-19-related hospitalizations in all regions.

HIV product sales increased 6% to $18.2 billion in the full year 2023, primarily reflecting higher demand across treatment and prevention, in addition to higher average realized price and favorable channel inventory dynamics. Flagship HIV treatment Biktarvy saw its sales increase 14% to $11.8 billion, primarily reflecting higher demand as well as higher average realized price.

The Liver Disease portfolio sales decreased 1% to $2.8 billion, primarily driven by unfavorable HCV pricing dynamics and foreign exchange rates, partially offset by higher demand across HCV, HDV and chronic hepatitis B virus (HBV) products.

Meanwhile, Cell Therapy product sales increased 28% to $1.9 billion in the full year 2023. Yescarta sales increased 29%, Tecartus sales increased 24% and Trodelvy sales increased 56%. Trodelvy is now approved for three types of cancer with multiple studies underway to explore additional opportunities.

In 2023, Gilead made progress on building its early pipeline and capabilities for treating inflammatory diseases through both internal innovation programs and collaborations with external partners. Notably, the company began 2024 by announcing its acquisition of CymaBay to complement and bolster its existing treatments for liver disease. This move is part of its larger goal of investing in strategic opportunities to expand its internal portfolio.

Acquisitions

In May 2023, Gilead Sciences acquired all outstanding shares of XinThera, a privately held biotech company in San Diego. The acquisition added clinical development pipeline assets for well-validated targets in oncology and inflammation.

Most significantly, Gilead completed the acquisition of CymaBay Therapeutics for approximately $4.3 billion in total equity value in March of 2024. The addition of CymaBay’s investigational lead product candidate, seladelpar for the treatment of primary biliary cholangitis (PBC) including pruritus, complements Gilead’s existing liver portfolio.

Seladelpar is an investigational, oral, selective peroxisome proliferator-activated receptor delta (PPARδ) agonist, shown to regulate critical metabolic and liver disease pathways. The United States Food and Drug Administration (FDA) has completed its filing review and accepted a New Drug Application for seladelpar and granted priority review with a Prescription Drug User Fee Act target action date of August 14, 2024.

Alliances

Gilead and its cell therapy company, Kite, have teamed up with several biotech companies to advance drug targets in inflammatory diseases and blood cancers. In July 2023, Gilead partnered with the Clinton Health Access Initiative (CHAI) and the Penta ID network, a scientific organization dedicated to child health research, to accelerate the development, regulatory approval and commercialization of a dispersible, fixed-dose combination treatment for the treatment of children with HIV who weigh at least 3 kg and live in low- and middle-income countries (LMICs).

In August 2023, Gilead Sciences and Tentarix Biotherapeutics established three multi-year collaborations leveraging Tentarix’s proprietary Tentacles platform to discover and develop multi-functional, conditional protein therapeutics for oncology and inflammatory diseases.

In October 2023, Gilead Sciences and Assembly Biosciences Inc. entered a 12-year partnership to advance the research and development of novel antiviral therapies, with an initial focus on Assembly Bio’s established areas of herpesviruses, hepatitis B virus (HBV) and hepatitis D virus (HDV). Also in October, Kite and Epicrispr Biotechnologies entered into a research collaboration and license agreement using Epic Bio’s proprietary gene regulation platform to develop next-generation cancer cell therapies.

In November 2023, Kite and Arcellx Inc. expanded their existing collaboration, which was originally announced in December 2022. Kite exercised its option to negotiate a license for Arcellx’s ARC-SparX program, ACLX-001, in multiple myeloma, which is comprised of ARC-T cells and SparX proteins that target BCMA. The companies also expanded the scope of the collaboration for Arcellx’s CART-ddBCMA to include lymphomas.

In December 2023, Gilead Sciences announced an agreement with Compugen Ltd., a clinical-stage cancer immunotherapy company and a pioneer in computational target discovery, to exclusively license its potential first-in-class, pre-clinical antibody program against IL-18 binding protein, including the COM503 drug candidate, a high affinity antibody which blocks the interaction between IL-18 binding protein and IL-18, thereby releasing natural IL-18 in the tumor microenvironment and inhibiting cancer growth.

In January 2024, Gilead Sciences and Arcus Biosciences Inc. announced an amendment to their collaboration agreement and a separate equity investment by Gilead of $320 million in Arcus common stock at $21.00 per share. The equity investment and collaboration amendment enable accelerated growth of the companies’ joint development programs that span multiple indications.

In March 2024, Gilead Sciences and Merus N.V. announced a research collaboration, option and license agreement to discover novel dual tumor-associated antigens (TAA) targeting trispecific antibodies. Also in March, Gilead and Xilio Therapeutics Inc. announced an exclusive license agreement to develop and commercialize Xilio’s Phase 1 tumor-activated IL-12 program, XTX301.

Approvals

In July 2023, the U.S. Food and Drug Administration (FDA) approved a supplemental new drug application (sNDA) for the use of Veklury (remdesivir) in COVID-19 patients with severe renal impairment, including those on dialysis. Also in July, the European Commission (EC) approved Trodelvy (sacituzumab govitecan) as a monotherapy for the treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-negative breast cancer who have received endocrine-based therapy, and at least two additional systemic therapies in the advanced setting.

In December, the FDA approved a label update for Yescarta (axicabtagene ciloleucel) to include the overall survival (OS) primary analysis from the landmark Phase 3 ZUMA-7 study showing a statistically significant improvement for Yescarta in OS versus standard of care (SOC) as second-line treatment with curative intent for patients with relapsed or refractory large B-cell lymphoma (R/R LBCL) within 12 months of completion of first-line therapy.

In January, the FDA approved a manufacturing process change resulting in a shorter manufacturing time for Yescarta (axicabtagene ciloleucel). With this approval, Kite’s median turnaround time (TAT) in the U.S. is anticipated to be reduced from 16 days to 14 days.

In February, the FDA approved a new, expanded indication for Biktarvy (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg tablets, B/F/TAF) to treat people with HIV (PWH) who have suppressed viral loads with known or suspected M184V/I resistance, a common form of treatment resistance.

In March, the FDA approved the sNDA for Vemlidy (tenofovir alafenamide) 25 mg tablets as a once-daily treatment for chronic hepatitis B virus (HBV) infection in pediatric patients six years of age and older and weighing at least 25 kg with compensated liver disease.

Most recently, in April, the FDA approved an updated label with additional data reinforcing the safety and efficacy profile of Biktarvy (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg tablets, B/F/TAF) to treat pregnant people with HIV-1 (PWH) with suppressed viral loads.

Headcount: 17,000
Revenues: $27,281 (flat)
Net Income: $4,566 (-26%)
R&D: $4,977 (+8%)

Despite flat sales in 2022, Gilead maintains its position at 13, with impressive growth in Oncology sales with growing demand for Trodelvy and Cell Therapies offset by a 30% drop in Veklury sales and expenses associated with the termination of the Trodelvy collaboration agreement with Everest, under which Gilead acquired remaining worldwide rights.

Flagship HIV treatment Biktarvy gained market share in the U.S., with sales up 20% and Trodelvy sales increased 79% to $680 million for the year. For Gilead’s franchises, HIV product sales increased 5% to $17.2 billion for the year, Cell Therapy product sales were up 68% to $1.5 billion and HBV and HDV product sales increased 2% to $988 million.

Notable highlights for the year include the company’s long-acting HIV agent, lenacapavir, received its first regulatory approvals, and several acquisitions added assets in oncology and inflammation, as well as next-generation CAR T-therapies.

CAR T manufacturing facilities

Kite, Gilead’s cell therapy company, received approval from the FDA for its retroviral vector (RVV) manufacturing facility in Oceanside, CA, for commercial production. Viral vectors are key components needed to manufacture Kite’s cell therapies to treat certain blood cancers. Kite is the only cell therapy company with in-house commercial and clinical trial viral vector manufacturing capabilities, augmenting its external supply partners.

The FDA also approved Kite’s commercial production at its new CAR T-cell therapy manufacturing facility in Frederick, MD. The site will produce Kite’s FDA approved CAR T-cell therapy used to treat blood cancer and increases capacity by 50% to meet demand.

Kite’s existing manufacturing facilities in California and Amsterdam, Netherlands form the largest in-house cell therapy manufacturing network in the world, spanning process development to commercial product manufacturing.

Acquisitions

Over the course of the year, Gilead expanded its pipeline with several acquisitions targeting oncology and inflammation, and next-generation CAR T-therapies. Gilead acquired MiroBio, a U.K.-based biotechnology company focused on restoring immune balance with agonists targeting immune inhibitory receptors, for approximately $405 million in cash.

MiroBio’s discovery platform and portfolio of immune inhibitory receptor agonists inlcudes lead investigational antibody, MB272, a selective agonist of immune inhibitory receptor B- and T-Lymphocyte Attenuator (BTLA) in Phase 1 trials. MB272 targets T, B and dendritic cells to inhibit or blunt activation and suppress an inflammatory immune response.

MiroBio’s I-ReSToRE platform has the potential to be used to develop best-in-class agonist antibodies targeting immune inhibitory receptors, a novel approach to the treatment of inflammatory diseases. Gilead anticipates advancing additional agonists derived from MiroBio’s I-ReSToRE platform, including a PD-1 agonist, MB151, and other undisclosed early-stage programs, over the next several years.

Gilead has acquired all outstanding shares of XinThera, a privately held biotech company in San Diego, adding clinical development pipeline assets for validated targets in oncology and inflammation. Through the acquisition, Gilead gains rights to a portfolio of small molecule inhibitors targeting PARP1 for oncology and MK2 for inflammatory diseases that could enter clinical trials later this year. Both programs have the potential to address multiple indications, offering broad development opportunities alone and in combination with Gilead’s portfolio.

Additionally, Gilead acquired remaining rights to GS-1811 from Jounce Therapeutics for $67 million. GS-1811, an anti-CCR8 antibody, is a potentially first-in-class immunotherapy designed to selectively deplete immunosuppressive tumor-infiltrating T regulatory cells in the tumor and is currently in Phase 1 development as a possible treatment for patients with solid tumors.

Lastly, Kite acquired Tmunity Therapeutics, a biotech company focused on next-generation CAR T-therapies and technologies. The acquisition complements Kite’s in-house cell therapy research capabilities, adding additional pipeline assets, platform capabilities, and a strategic research and licensing agreement with the University of Pennsylvania. Preclinical and clinical programs include an ‘armored’ CAR T technology platform, which potentially could be applied to a variety of CAR T’s to enhance anti-tumor activity, as well as rapid manufacturing processes.

Alliances

Gilead and its cell therapy company, Kite, have teamed up with several biotech companies to advance drug targets in inflammatory diseases and blood cancers. Gilead paid $35 million upfront to expand its partnership with Arcus to include inflammation research programs against up to four jointly selected targets. If Gilead exercises its option for the first two target programs, Arcus would be eligible to receive as much as $420 million in milestone payments and royalties for each optioned program.

Exercising its option to exclusively license Nurix’s Therapeutics investigational targeted protein degrader molecule NX‑0479, Gilead paid $20 million with Nurix eligible to receive an additional $425 million in clinical, regulatory, and commercial milestones. The bivalent degrader, designated GS-6791, is the first development candidate resulting from the previously announced Nurix-Gilead collaboration to develop and commercialize a pipeline of innovative targeted protein degradation therapies.

GS-6791 is a potent, selective, oral IRAK4 degrader designed to block inflammatory responses downstream of toll-like receptors and the pro-inflammatory IL1 cytokine family of receptors. IRAK4 degradation has potential applications in the treatment of rheumatoid arthritis and other inflammatory diseases.

Meanwhile, Kite entered a global strategic collaboration to co-develop and commercialize Arcellx’s lead late-stage product candidate, CART-ddBCMA, for the treatment of relapsed or refractory multiple myeloma. Currently in Phase 2, CART-ddBCMA is an investigational cell therapy comprising autologous T cells that have been genetically modified to target multiple myeloma.

Arcellx received $225 million upfront and $100 million equity investment. Kite is responsible for the development and commercialization costs for any product under the collaboration that is not co-commercialized. After completion of the technical transfer, Kite will be responsible for manufacturing.

Additionally, to develop potential treatments for blood cancers, Kite entered an exclusive, worldwide license agreement for exclusive rights to use Refuge Biotechnologies’ gene expression platform, a synthetic biology system that uses an expression modulation strategy to repress or activate transcription of target genes. Preclinical data suggests a potential for this highly modular platform to regulate target antigen-dependent gene expression as a means to improve upon both the efficacy and safety of first-generation CAR T-cell therapies. Kite will have an exclusive license to Refuge’s intellectual property portfolio for use in blood cancers, as well as a library of synthetic gene expression programs for these indications.

Approvals

In December, Sunlenca (lenacapavir) received FDA approval as a first-in-class, twice-yearly treatment option for people living with multi-drug resistant HIV, becoming the first and only approved capsid inhibitor-based HIV treatment. This new type of medication is for the most common variant of HIV, HIV-1.

Sunlenca was also granted approval by the European Commission supported by data from the Phase 2/3 CAPELLA study. In this patient population, 83% of participants receiving lenacapavir in addition to an optimized background regimen achieved an undetectable viral load.

Additionally, the FDA approved Trodelvy for the treatment of unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. The approval is based on statistically significant and clinically meaningful progression-free survival and overall survival data from the Phase 3 TROPiCS-02 study.

Headcount: 14,400
Revenues: $27,305 (+11%)
Net Income: $6,225
R&D: $5,363 (+8%)

TOP SELLING DRUGS

Gilead delivered strong financial performance in 2021, driven by the increased demand for Veklury (remdesivir), the strong underlying demand for its virology products and increased contributions from the oncology franchise.

Total product sales of $27 billion grew 11% year-over-year with Veklury sales, which grew 98%, contributing $5.6 billion in 2021. HIV sales of $16.3 billion were down 4% compared with 2020, reflecting the loss of exclusivity of Truvada and Atripla in the U.S. Aside from the loss of exclusivity impact, HIV sales grew 4%, driven by the continued strong performance of Biktarvy. Oncology sales were $1.25 billion in 2021, with cell therapy sales of $871 million growing 43% compared with 2020 and Trodelvy sales of $380 million.

During the year, Gilead strengthened its portfolio with several key approvals. First, a new low-dose tablet form of Biktarvy received the FDA green light for pediatric patients who are virologically suppressed or new to antiretroviral therapy.

Cancer drug Trodelvy was approved in the U.S., EU, Australia, Canada, Great Britain and Switzerland as a second line treatment for metastatic triple-negative breast cancer. It was also granted FDA accelerated approval for adults with locally advanced or metastatic urothelial cancer, the most common type of bladder cancer.

Cell therapy approvals

On the cell therapy front, Gilead received a couple of historic approvals during the year together with Kite Pharma, the cell therapy business it acquired back in 2017. In March 2021, Yescarta was granted FDA accelerated approval for the treatment of adults with relapsed or refractory follicular lymphoma after two or more lines of systemic therapy. This was the first CAR T-cell therapy approved for this indication. Yescarta also received FDA Breakthrough Therapy Designation and was the third approved indication for a Kite Pharma CAR T-cell therapy.

In October 2021, Kite received FDA approval for Tecartus to treat adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia, representing the first CAR T-cell therapy approved for adults living with this disease. This marked Kite’s fourth FDA-approved indication in CAR T-cell therapy in under four years and its first in leukemia.

In other cell therapy news, Gilead was successful during the year in bringing CAR-T to patients in Asia. Fosun Kite Biotechnology Co., Ltd., a joint venture between Kite and Shanghai Fosun Pharmaceutical (Group) Co., Ltd, gained the first CAR T-cell therapy approval in China for the treatment of relapsed or refractory LBCL in adults. Also, at the end of 2021, Kite and Daiichi Sankyo announced that Yescarta will be available to people with relapsed or refractory LBCL in Japan through the first treatment center now authorized by Daiichi Sankyo.

The fight against COVID-19

In 2021, Veklury continued to play a key role in the COVID-19 pandemic. This antiviral therapy is approved or authorized in more than 50 countries, and it is the antiviral standard of care for the treatment of hospitalized patients with COVID-19. Veklury and generic remdesivir have been made available to more than 10 million patients around the world, including approximately 3 million people in the developed world and nearly 7 million people in 127 low- and lower middle- income countries through Gilead’s royalty-free voluntary licensing program. Throughout 2021, Gilead continued to support its voluntary licensing partners to rapidly scale production to meet the evolving global demands for treatment as the virus mutated and surged.

In December 2021, The New England Journal of Medicine published data that showed a three-day course of remdesivir significantly reduced the risk of hospitalization in people with COVID-19 at high risk for disease progression. These data led to FDA approval in early 2022 of an expanded indication for Veklury for adult and adolescent COVID-19 patients who are not hospitalized and are at high risk of progression to severe COVID-19. In addition, the FDA granted an expanded pediatric emergency use authorization for non-hospitalized patients under age 12 at high risk of progression.

Acquisition and collaboration

In March 2021, Gilead closed its €1.15 billion acquisition of MYR GmbH, a company focused on developing therapies for the treatment of chronic hepatitis delta virus (HDV), the most severe form of viral hepatitis. This began the work of delivering on the potential of Hepcludex (bulevirtide), the first-in class therapy conditionally authorized by the European Medical agency to address the high unmet need in HDV. A Biologics License Application was filed to the FDA in November 2021. If approved, bulevirtide will be the first treatment option for this disease in the U.S.

In the HIV arena, Gilead and Merck entered into an agreement to co-develop and co-commercialize long-acting treatments in HIV that combine Gilead’s investigational capsid inhibitor, lenacapavir, and Merck’s investigational nucleoside reverse transcriptase translocation inhibitor, islatravir, into a two-drug regimen with the potential to provide new treatment options for people living with HIV. The collaboration is initially focusing on long-acting oral formulations and long-acting injectable formulations of these combination products, with other formulations potentially added to the collaboration.

Across the oral and injectable formulation programs, Gilead and Merck will share global development and commercialization costs 60% and 40%, respectively. For long-acting oral products, Gilead will lead commercialization in the U.S. and Merck will lead commercialization in the EU and rest of the world. For long-acting injectable products, Merck will lead commercialization in the U.S. and Gilead will lead commercialization in the EU and rest of the world.

In other HIV news, Gilead entered into a collaboration, option and license agreement with Gritstone Oncology to research and develop a vaccine-based immunotherapy as part of Gilead’s efforts to find a curative treatment for HIV infection.

Gilead accelerated clinical development in oncology with Arcus Biosciences by exercising options to three programs in Arcus’ clinical-stage portfolio across lung, colon, prostate and pancreatic cancers with payments to Arcus totaling $725 million.

Kite’s collaboration with Appia Bio is harnessing the properties of natural killer T-cells to research and develop allogeneic CAR T-cell therapies for blood cancers while a research deal with Oxford BioTherapeutics is evaluating five novel targets for blood cancer and solid tumors.

Following a 2021 investment in Shoreline Biosciences’ Series A financing, Gilead formed a partnership to develop novel allogeneic CAR T-cell therapies against a variety of cancers including leukemias and lymphomas.

A clinical trial collaboration with Merck was announced to evaluate Trodelvy in combination with Keytruda in the first-line setting in patients with metastatic TNBC and, in the first quarter 2022, in patients with non-small cell lung cancer.

With Dragonfly Therapeutics, Gilead recently entered a collaboration to advance a number of Dragonfly’s novel natural killer cell engager-based immunotherapies for oncology and inflammation indications. Natural killer cell engagers represent a novel mechanism with the potential to address a broad range of cancers, including potential for activity in checkpoint resistant and refractory tumors, as well as other disease areas such as inflammation.

Gilead has also expanded a clinical collaboration with Novo Nordisk in non-alcoholic steatohepatitis (NASH) and continues to advance a 10-year collaboration with Galapagos in inflammation.

Headcount: 13,000
Revenues: $24,689 (+10%)
Net Income: $123 (-98%)
R&D: $5,039 (+24%)

TOP SELLING DRUGS

In 2020 Gilead reported revenues of $24.7 billion, up 10% primarily due to the launch of Veklury (remdesivir). Product sales excluding Veklury for year decreased 3% due to the continued effects of Covid-19 on Gilead’s HIV and hepatitis C virus (HCV) franchises, as well as the expected decline in sales of Truvada-based products due to the loss of exclusivity of Truvada and Atripla in the U.S. in October 2020. Despite these challenges, Gilead continues to make pipeline progress, along with efforts to diversify its portfolio, and further expand into immune-oncology with significant investments.

Looking ahead, in the first quarter of 2021 revenues were up 16%, driven by Veklury sales, cell therapy growth with Yescarta and the U.S. launch of Tecartus in the third quarter 2020, the first full quarter recognition of Trodelvy sales, and Hepatitis B virus (HBV) growth with Vemlidy.

Covid news
As one of the foremost anti-viral experts in the industry, it’s not a surprise that Gilead succeeded in being the first company to provide a potential therapy for Covid-19. Veklury was initially approved in Japan on May 7, 2020 under an exceptional approval pathway for patients infected with SARS-CoV-2. Later that year, it was authorized by the FDA for emergency use to treat Covid-19. Finally, in October 2020, the FDA approved Veklury for the treatment of patients with Covid-19 requiring hospitalization, making it the first and only approved Covid-19 treatment in the U.S.

As an antiviral drug, Veklury works to stop replication of SARS-CoV-2, the virus that causes Covid-19. The approval was based on three trials, which showed that treatment with Veklury resulted in clinically meaningful improvements across multiple outcome assessments compared with placebo in hospitalized patients with Covid-19. By the end of 2020, one million people in the U.S. had received Veklury.

Approvals
In July 2020, Kite, a Gilead Company, was granted accelerated approval for Tecartus, the first and only approved chimeric antigen receptor (CAR) T cell therapy for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL). The approval of this one-time therapy follows a priority review and FDA Breakthrough Therapy Designation and is based on the ZUMA-2 study in which 87 percent of patients responded to a single infusion of Tecartus, including 62 percent of patients achieving a complete response (CR). Tecartus will be manufactured in Kite’s commercial manufacturing facility in El Segundo, CA.

In September, the FDA granted Breakthrough Therapy designation for magrolimab, a first-in-class, investigational anti-CD47 monoclonal antibody for the treatment of newly diagnosed myelodysplastic syndrome (MDS). The designation for magrolimab was based on positive results of an ongoing Phase 1b study, which evaluated magrolimab in combination with azacitidine in previously untreated intermediate, high and very high-risk MDS.

The FDA also granted accelerated approval to Yescarta for the treatment of adults with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy. The approval makes Yescarta the first chimeric antigen receptor (CAR) T-cell therapy approved for patients with indolent follicular lymphoma and is based on results from ZUMA-5, a single-arm, open-label study in which 91 percent of patients responded to Yescarta, including an estimated 74 percent in a continued remission at 18 months.

Most recently, the FDA approved Trodelvy for adults with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease. The approval is supported by data from a Phase 3 study, in which Trodelvy demonstrated a statistically significant and clinically meaningful 57% reduction in the risk of disease worsening or death. Trodelvy also extended median overall survival to 11.8 months vs. 6.9 months, representing a 49% reduction in the risk of death.

Furthermore, the FDA approved Trodelvy for use in adults with locally advanced or metastatic urothelial cancer (UC) who have previously received a platinum-containing chemotherapy and either a programmed death receptor-1 (PD-1) or a programmed death-ligand 1 (PD-L1) inhibitor. The accelerated approval was based on data from a Phase 2 study. Of the 112 patients who were evaluable for efficacy, 27.7% of those treated with Trodelvy responded to treatment, with 5.4% experiencing a complete response and 22.3% experiencing a partial response.

Acquisitions
Known for investing big in R&D, Gilead spent $25.7 billion on acquisitions in fiscal year 2020. In July 2020, the company invested $300 million to acquire a 49.9% equity interest in Tizona Therapeutics Inc., a privately held company developing first-in-class cancer immunotherapies. Gilead also received an exclusive option to acquire the remainder of Tizona for up to an additional $1.25 billion. The U.S. FDA recently cleared Tizona’s Investigational New Drug (IND) application for TTX-080.

In October 2020, Gilead acquired Immunomedics in a transaction valued at approximately $21 billion. The agreement provided Gilead with Trodelvy and represents significant progress in Gilead’s work to build a strong and diverse oncology portfolio.

Gilead also acquired MYR, a German biotechnology company focused on therapeutics for the treatment of chronic hepatitis delta virus (HDV), for approximately $1.4 billion in cash, plus a potential future milestone payment of up to $357 million. Gilead gains Hepcludex (bulevirtide), which was conditionally approved by the European Medicines Agency for the treatment of chronic HDV infection in adults with compensated liver disease in July 2020. MYR has since launched Hepcludex in France, Germany and Austria, and continues to prepare for launch in certain other markets throughout 2021.

Collaborations
Gilead entered into several strategic partnerships during the year, especially in the field of oncology, an important new pillar of growth for the company. In August 2020, the company expanded a strategic collaboration with Tango Therapeutics focused on the discovery, development and commercialization of targeted immune evasion therapies for patients with cancer.

Also, Gilead entered an agreement with Jounce Therapeutics Inc., a company focused on novel cancer immunotherapies and predictive biomarkers, to exclusively license its JTX-1811 program. JTX-1811 is a monoclonal antibody designed to selectively deplete immunosuppressive tumor-infiltrating T regulatory cells.

In December, Gilead and Galapagos NV amended their existing arrangement for the commercialization and development of Jyseleca (filgotinib). Following an FDA Type A meeting, Gilead decided not to advance Jyseleca for the treatment of Rheumatoid Arthritis. Under the new arrangement, Galapagos will assume sole responsibility in Europe for filgotinib in RA, where 200 mg and 100 mg doses are approved for moderate to severe RA, and in all future indications.

In January 2021 Kite entered a research collaboration with Oxford BioTherapeutics Ltd. (OBT) to evaluate five novel targets for a number of hematologic and solid tumor indications. OBT will validate five oncology targets and generate antibodies against these targets. Kite and Gilead will have the exclusive right to develop and commercialize therapies based on these targets or antibodies.

Also in January, Gilead and Vir Biotechnology entered a clinical collaboration to evaluate therapeutic combination strategies aimed at developing a functional cure for chronic hepatitis B virus.

An agreement with Gritstone Oncology aims to develop a vaccine-based immunotherapy as a curative treatment for HIV infection. The alliance will leverage Gritstone’s prime-boost vaccine platform, comprised of self-amplifying mRNA (SAM) and adenoviral vectors, with antigens developed by Gilead.

Recently, Gilead and Merck agreed to co-develop and co-commercialize long-acting treatments in HIV that combine Gilead’s investigational capsid inhibitor, lenacapavir, and Merck’s investigational nucleoside reverse transcriptase translocation inhibitor, islatravir, into a two-drug regimen with the potential to provide new, meaningful treatment options for HIV. The first clinical studies of the oral combination are expected to begin in the second half of 2021.

Gilead also expanded its non-alcoholic steatohepatitis (NASH) alliance with Novo Nordisk. The companies will conduct a Phase 2 study to investigate the safety and efficacy of Novo’s semaglutide and a fixed-dose combination of Gilead’s FXR agonist cilofexor and investigational ACC inhibitor firsocostat, alone and in combination in compensated cirrhosis due to NASH.

Headcount: 12,000
Revenues: $22,449 (+1%)
Net Income: $5,364 (-2%)
R&D: $9,106 (+81%)

TOP SELLING DRUGS

Despite a relatively flat fiscal year, Gilead continues to make pipeline progress, along with efforts to diversify its portfolio, and further expand into immuno-oncology with significant investments, namely the acquisition of Forty Seven and an extensive alliance with Arcus Biosciences.

Looking ahead, in the first quarter of 2020 revenues were up 5% driven by HIV product sales of $4.1 billion, up 14% thanks to continued uptake of Biktarvy with $1.7 billion in sales, and the company’s CAR-T cancer therapy Yescarta, which generated $140 million in sales in the quarter compared to $96 million in 1Q19. There’s reason to believe the company’s flagship HIV franchise and foray into CAR-T therapies will more than compensate for continued declines in chronic hepatitis C virus (HCV) sales, which were down 8% in 1Q20.

Top News
As one of the foremost anti-viral experts in the industry, it’s not surprising that the company succeeded in being the first to provide a potential therapy for COVID-19. Remdesivir was approved in Japan on May 7 under an exceptional approval pathway as a treatment for patients infected with SARS-CoV-2. The FDA has granted the drug an Emergency Use Authorization for the treatment of hospitalized patients with severe COVID-19, however the authorization is temporary.

Remdesivir is an investigational nucleotide analog with broad-spectrum antiviral activity both in vitro and in vivo in animal models against multiple emerging viral pathogens, including Ebola, Marburg, MERS and SARS.

On June 1, Gilead announced results from the Phase III trial of Remdesivir in patients with moderate COVID-19. The SIMPLE trial in hospitalized patients with moderate COVID-19 pneumonia evaluated 5-day and 10-day courses of the investigational antiviral remdesivir plus standard of care, versus standard of care alone. The study demonstrated that patients in the 5-day remdesivir treatment group were 65 percent more likely to have clinical improvement at Day 11 compared with those in the standard of care group. The odds of improvement in clinical status with the 10-day treatment course of remdesivir versus standard of care were also favorable, trending toward but not reaching statistical significance.

In an effort to expand access to the investigational remdesivir for the potential treatment of COVID-19, Gilead entered a global collaboration and license agreement with Mylan, giving Mylan rights to manufacture and distribute remdesivir in 127 low- and middle-income countries, including India. To ensure preparedness, Mylan will develop a bioequivalent version of the drug, including production of its own active pharmaceutical ingredient and finished dosage form in sterile powder lyophilized vials for intravenous infusion.

Expanded Approvals & Filings
Marking a couple of significant approvals for the company, the FDA approved a pre-exposure prophylaxis (PrEP) indication for Descovy to reduce the risk of sexually acquired HIV-1 infection in adults and adolescents who are HIV-negative and at-risk, which was approved under a priority review designation.

The FDA also approved Epclusa for children ages 6 and older with Hepatitis C Virus. Epclusa is the first pan-genotypic, protease inhibitor-free regimen approved in the U.S. for children and adults. An estimated 23,000 to 46,000 children in the U.S. are living with HCV.

Reaching a key milestone, Gilead submitted an NDA to the FDA for filgotinib, an investigational, oral, selective JAK1 inhibitor for the treatment of moderate-to-severe rheumatoid arthritis (RA). The filing is supported by a Phase III program, which met its primary endpoints and demonstrated durable efficacy and safety results across multiple RA patient populations.

R&D Efforts
Gilead is working on multiple investigational compounds for the treatment of advanced fibrosis due to Nonalcoholic Steatohepatitis (NASH), including firsocostat, cilofexor, and selonsertib. The company is evaluating single-agent and combination therapy approaches against the core pathways associated with NASH – hepatocyte lipotoxicity, inflammation and fibrosis.

However, NASH, a complex disease driven by multiple mechanisms, is proving to be a challenge. Gilead’s Phase III STELLAR-3 study evaluating the safety and efficacy of selonsertib, an investigational, once daily, oral inhibitor of apoptosis signal-regulating kinase 1 (ASK1), for patients with bridging fibrosis due to NASH, did not meet the primary endpoint of a histologic improvement in fibrosis without worsening of NASH.

Similarly, a Phase II ATLAS study of combination and monotherapy investigational treatments, firsocostat and cilofexor, in advanced fibrosis due to NASH, did not meet the primary endpoint, although some improvement was seen in response measures of fibrosis and liver function compared with placebo.

Despite these disappointing results, the company says it remains focused and committed to developing effective treatments for patients living with advanced fibrosis due to NASH. Gilead is also collaborating with Novo Nordisk on a study combining Gilead’s cilofexor and firsocostat and Novo Nordisk’s semaglutide for the treatment of NASH.

Among recent pipeline progress, in late May, Kite, a Gilead Company, reported positive interim analysis of ZUMA-5, a global Phase II study evaluating Yescarta in patients with relapsed or refractory indolent (slow growing) non-Hodgkin lymphoma (NHL) after at least two prior lines of therapy. After a single infusion of Yescarta, 93 percent of patients responded, with an impressive 80 percent achieving a complete response.

Pending final results, Kite plans to submit a sBLA to the FDA later this year to expand the indication for Yescarta. If approved, it would become the first and only chimeric antigen receptor (CAR) T therapy approved for the treatment of relapsed or refractory indolent NHLs.

Also, Kite achieved two key regulatory milestones for KTE-X19, an investigational cell therapy for the treatment of relapsed or refractory mantle cell lymphoma. In Europe, the marketing authorization application for KTE-X19 is under review, and in the U.S., the FDA accepted the Biologics License Application and it was granted Priority Review Designation.

Investments
Known for investing big in R&D, Gilead recently entered an agreement to acquire Forty Seven, Inc. in a transaction valued at approximately $4.9 billion. The acquisition strengthens Gilead’s immuno-oncology portfolio with the addition of Forty Seven’s investigational lead candidate, magrolimab, a monoclonal antibody in clinical development for the treatment of several cancers including myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) and diffuse large B-cell lymphoma (DLBCL).

The investigational therapy targets CD47, a “do not eat me” signal that allows cancer cells to avoid destruction, allowing the patient’s own immune system to eradicate those cancer cells. A Phase 1b study of magrolimab in patients with MDS and AML showed the potential for it to be a first-in-class therapy.

Gilead also recently entered a 10-year partnership with Arcus Biosciences valued at nearly $2 billion to develop current and future therapeutic candidates in Arcus’s pipeline of products that target key mechanisms involved in tumor evasion of the immune system, as well as drug candidates that target cell-intrinsic pathways important for cancer growth and metastasis. In addition to small molecule products, Arcus is also advancing antibody products that target immune checkpoint receptors, including PD-1 and TIGIT.

Gilead gains rights to zimberelimab, as well as the right to opt-in to all other current Arcus clinical candidates, which include AB154, AB928 and AB680.

Similarly, last July, Gilead entered a 10-year global research and development collaboration with Galapagos providing access to a portfolio of compounds, including six molecules currently in clinical trials, more than 20 preclinical programs and a proven drug discovery platform. Gilead paid $3.95 billion upfront and made a $1.1 billion equity investment in Galapagos in exchange for exclusive product license and option rights to develop and commercialize all current and future programs.

Galapagos most advanced molecule, GLPG1690, is in Phase III development for idiopathic pulmonary fibrosis, which has shown a reduction in signs and symptoms of IPF. GLPG1972 is a Phase IIb candidate for osteoarthritis, and first-in-class compounds GLPG1690 and GLPG1972, could offer important mid- and late-stage pipeline opportunities for Gilead.

Expanding Cell Therapy Efforts
Lastly, several cell therapy alliances expand Gilead’s oncology efforts. A research pact with oNKo-innate aims to develop next-generation drug and engineered cell therapies focused on natural killer (NK) cells. Like T cells, NK cells are a class of white blood cells that play a critical surveillance and effector role in the immune system. Appropriately activated and targeted NK cells may represent a differentiated approach that would be potentially synergistic with T cell mediated anti-tumor strategies.

Additionally, Kite and Teneobio entered into a license and collaboration agreement through which Kite will receive exclusive rights to certain antibodies directed to B-cell maturation antigen (BCMA). The fully human variable heavy chain of one such antibody is currently undergoing Phase I evaluation in a chimeric antigen receptor (CAR) format for the treatment of multiple myeloma. The companies are also working on the discovery of antibodies directed to four additional targets using Teneobio’s UniAb platform to be used in CAR-T cell therapies for multiple myeloma and other cancers.

To accommodate this growing pipeline of cell therapies, Kite is building a new 67,000-sq.-ft. facility in Oceanside, CA, dedicated to the development and manufacture of viral vectors, a critical starting material in the production of cell therapies.

Headcount: 11,000
Revenues: $22,127 (-15%)
Net Income: $5,455 (+18%)
R&D: $5,018 (+34%)

TOP SELLING DRUGS

Climbing out of a two-year downturn, the light at the end of the tunnel revealed itself in the first quarter of 2019, with revenues up 4% to $5.3 billion and earnings up 28% to $2.0 billion. Still recovering financially from HCV franchise declines, Gilead has finally returned to growth thanks to its flagship HIV franchise and Yescarta, its first commercially available CAR-T cancer therapy.

While chronic hepatitis C virus (HCV) product sales, which consist of Epclusa, Harvoni, Vosevi, and Sovaldi, were down nearly 60% to $3.7 billion in 2018, and down 26% in the first quarter of 2019 to $790 million, HIV product sales were up 12% to $14.6 billion for the year, primarily due to the launch of Biktarvy and the continued uptake of Descovy, Genvoya and Odefsey. In 1Q19, HIV product sales were up 13% to $3.6 billion, thanks to Biktarvy.

Yescarta, a chimeric antigen receptor (CAR) T cell therapy launched in the U.S. in October 2017 to treat large B-cell lymphoma, generated $264 million in sales in 2018. Resulting from the 2017 acquisition of Kite Pharma, Yescarta was the second gene therapy approved by the FDA and the first for certain types of non-Hodgkin lymphoma (NHL). Yescarta generated $96 million in sales in the first quarter compared to $40 million in 1Q18.

Kite Pharma, a Gilead company, is significantly expanding its ability to manufacture a variety of CAR-T therapies, including Yescarta, for both clinical and commercial use with a new biologics facility in Urbana, MD. Kite specializes in cancer treatments and the facility will focus on chimeric antigen receptor T (CAR-T) therapies, which uses a patient’s white blood cells to destroy cancer cells. Producing these therapies requires complex processes and the new facility aims to better meet these specifications. It will become part of Kite’s commercial manufacturing network that includes sites in CA and the Netherlands. Yescarta is also being investigated in solid tumors. To date, CAR-T therapies have only proven successful in blood cancers.

Executive moves
As of March 1, 2019, Daniel O’Day took the helm as Gilead’s chairman and chief executive officer, succeeding John F. Milligan, Ph.D., who stepped down after a 28-year career with the company. Mr. O’Day previously served as CEO of Roche Pharmaceuticals, a position he held since 2012, and prior to that led Roche Diagnostics. His career spans three decades of leadership roles across North America, Asia Pacific and Europe.

In other recent executive moves, Gilead appointed Johanna Mercier as its new chief commercial officer, joining the senior leadership team on July 1, and succeeding Laura Hamill, who is departing from Gilead after less than a year in the role.

Also, Robin Washington, executive vice president and chief financial officer, plans to retire from her role, effective March 1, 2020, and Alessandro Riva, MD, executive vice president, Oncology Therapeutics, has decided to leave the company to pursue another opportunity. The company has yet to name successors for these two roles.
R&D
Updates to Gilead’s HIV and liver diseases programs include approvals in China of Harvoni for the treatment of HCV genotype 1-6 infection, Vemlidy for the treatment of chronic HBV infection, and Descovy for the treatment of HIV-1 infection. Also, findings from two studies support the further development of GS-6207, a first-in-class, investigational capsid inhibitor, which may represent a novel approach to HIV treatment due to its long-acting characteristics and potent antiviral activity seen in vitro.

However, recent results from a Phase III study evaluating the safety and efficacy of selonsertib, an investigational, once daily, oral inhibitor of apoptosis signal-regulating kinase 1 (ASK1), for patients with bridging fibrosis due to nonalcoholic steatohepatitis (NASH), did not meet its primary endpoint of improvement in fibrosis without worsening of NASH.

Gilead’s oncology and cell therapy programs recently achieved promising study results from a Phase I/II study evaluating KTE-X19, an investigational CD19 chimeric antigen receptor T cell therapy, in relapsed or refractory acute lymphoblastic leukemia. With a median follow-up of 15 months following a single infusion of KTE-X19, 69% of patients achieved complete tumor remission, and the rate of undetectable minimal residual disease in patients who achieved complete tumor remission was 100%.

Also, two-year efficacy and safety data of  Yescarta in patients with refractory large B-cell lymphoma, showed 39% of patients were in an ongoing response with a median follow up of 27 months.
Additionally, results from an ongoing Phase III study of filgotinib, an investigational, oral, selective JAK1 inhibitor, in moderate-to-severe active rheumatoid arthritis, achieved its primary endpoint of patients achieving an American College of Rheumatology 20 percent response (ACR20) at Week 24. The proportion of patients achieving the primary endpoint was significantly higher for filgotinib 200 mg plus MTX and filgotinib 100 mg plus MTX compared with MTX alone.

Lastly, a Phase II study of filgotinib in severe active ankylosing spondylitis (AS) achieved its primary endpoint of significantly greater improvements in AS Disease Activity Score at Week 12, with a mean change from baseline of -1.5 versus -0.6 for those treated with placebo. More patients receiving filgotinib also achieved an ASAS20 response compared to those treated with placebo.

Major investments
In its most recent deal, Gilead will pay Nurix Therapeutics $45 million up front and as much as $2.3 billion in milestones under a global strategic collaboration to develop and commercialize a pipeline of innovative targeted protein degradation drugs for cancer and other challenging diseases. Dysregulated and/or mutated proteins play a central role in the development and progression of many human diseases. Nurix’s technology platform is focused on the manipulation of the ubiquitin system and its component E3 ligases, the key enzymes responsible for controlling protein levels in human cells.
Under an alliance with Agenus, Inc. focused on the development and commercialization of novel immuno-oncology therapies, Agenus will receive $150 million upfront including $30 million equity investment, and the agreement also includes approximately $1.7 billion in potential milestones.

A strategic collaboration with Scholar Rock Holding Corp. aims to discover and develop highly specific inhibitors of transforming growth factor beta activation for the treatment of fibrotic diseases. Scholar Rock will receive $80 million upfront in payments, including the purchase of Scholar Rock stock, and the company is eligible to receive up to an additional $1.4 billion in potential payments across three programs.

Moreover, a global strategic collaboration with Tango Therapeutics aims to develop and commercialize a pipeline of innovative targeted immuno-oncology treatments. Tango will receive $50 million upfront and is eligible to receive approximately $1.7 billion in additional payments across all programs.

Finally, Gilead is not giving up on nonalcoholic steatohepatitis (NASH) and has partnered with several companies to help advance its efforts. Gilead and Novo Nordisk are collaborating on a clinical trial combining compounds from their respective pipelines in NASH. The trial will combine Novo Nordisk’s semaglutide (GLP-1 analogue) and Gilead’s cilofexor (FXR agonist) and firsocostat (ACC inhibitor). The companies are also exploring the potential to collaborate on preclinical research to advance understanding of the disease.

Under a licensing and collaboration deal with Yuhan Corp. to develop novel NASH candidates, Gilead acquired global rights to small molecules against two targets for $15 million upfront and up to an additional $770 million in potential milestones.

Lastly, Gilead and insitro partnered to discover and develop NASH therapies leveraging insitro’s Human (ISH) platform to create disease models for NASH and discover targets that have an influence on clinical progression and regression of the disease. The insitro Human (ISH) platform applies machine learning, human genetics and functional genomics to generate and optimize unique models to drive discovery and development. Gilead can advance up to five targets identified through this collaboration.

Headcount: 9,000
Revenues: $26,107  (-13%)
Net Income: $4,628 (-66%)
R&D: $3,734 (-27%)

TOP SELLING DRUGS  

Antiviral product sales for Gilead, which make up the bulk of its revenue and include HIV, chronic hepatitis B (HBV) and chronic hepatitis C (HCV) products, were $23.3 billion compared to $27.7 billion in 2016. Sales dipped across the board for most of Gilead’s top selling drugs. Most notably, HCV drug Harvoni dropped 52% to $4.3 billion andSolvaldi fell 76% to $966 million, as a result of heavy competition in the HCV market. Top HIV drugs Truvada, Atripla and Stribild all fell 12%, 30% and 45% respectively. Poor sales were partially off-set by the strong growth of HIV drug Genvoya, which jumped 148% to $3.7 billion and is now the company’s top selling drug in the category.

More positive news emerged from Gilead’s other products category. Letairis for pulmonary hypertension grew 8% to $887 million and Ranexa for angina climbed 6% to $717 million.

All in all, while 2017 proved to be a lackluster year for Gilead—total revenue dropped 13% to $26 billion—the company is poised for better times ahead driven by its efforts in oncology.

Expanding oncology leadership

During 2017 Gilead made a big push to establish itself as a leader in oncology with a couple of acquisitions designed to advance and accelerate research and development efforts in cancer immunotherapy and other cell-based therapies. First in October it bought Kite Pharma for $11.9 billion. It was the second largest deal of the year behind J&J’s $30 billion purchase of Actelion. A few months later in December it paid $567 million for Cell Design Labs. With the acquisitions, Gilead gains a portfolio of CAR-T and TCR cell therapy candidates and manufacturing capabilities.

Kite specializes in cell therapies, which use a patient’s own immune cells to fight cancer. The company has developed engineered cell therapies that express either a chimeric antigen receptor (CAR) or an engineered T cell receptor (TCR). The company’s most advanced candidate, axicabtagene ciloleucel (axi-cel), is a CAR-T therapy that at the time of the deal was under priority review by the FDA for refractory aggressive non-Hodgkin lymphoma, including diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (TFL) and primary mediastinal B-cell lymphoma (PMBCL).

Kite also has additional candidates in clinical trials in both hematologic cancers and solid tumors, including KITE-585, a CAR-T therapy candidate that targets the B cell maturation antigen (BCMA) expressed in multiple myeloma.

Cell Design Labs is a company developing innovative technologies designed to bring greater precision and control to cancer treatment through custom cell engineering. The company’s ON-OFF switches and synthetic Notch receptors have the potential to enable T cells to more accurately recognize and target cancer and other disease tissues. The addition of Cell Design Labs’ technologies to existing Kite research and development programs could lead to the treatment of a broader range of hematological malignancies and solid tumors and enable development of treatments that are potentially safer and more effective. Cell Design’s pipeline includes early stage treatments for prostate cancer and blood cancer.

Pipeline highlights

In HIV, Gilead submitted a new drug application (NDA) with FDA and a marketing authorization application (MAA) with the European Medicines Agency (EMA) for Biktarvy, a once-daily single tablet regimen containing bictegravir, a novel investigational integrase strand transfer inhibitor, emtricitabine and tenofovir alafenamide (TAF) for the treatment of HIV infection in adults. In February 2018, Gilead received approval for Biktarvy in the U.S.

In oncology, shortly after acquiring Kite, Gilead received FDA approval for Yescarta (axicabtagene ciloleucel), the first CAR-T cell therapy for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy. In liver diseases, Gilead continued to advance the treatment of chronic hepatitis C virus (HCV) infection with the approval of Vosevi, a single tablet regimen for the re-treatment of adults with chronic HCV infection.

In 2017, Sovaldi for the treatment of chronic HCV infection received approval in China and is the first product Gilead launched directly in China. It also received European Commission approval of Vemlidy (TAF), a once-daily treatment for adults with chronic hepatitis B virus (HBV) infection with compensated liver disease.

In addition, Gilead continued to advance multiple ongoing clinical studies for the treatment of nonalcoholic steatohepatitis (NASH), which include the evaluation of selonsertib in two ongoing Phase III studies. In the area of inflammation/respiratory diseases, Gilead continued to advance filgotinib, a JAK1 inhibitor in development with Galapagos NV, in five ongoing Phase III clinical trials for the potential treatment of rheumatoid arthritis, Crohn’s disease and ulcerative colitis. At the end of 2017, Gilead’s research and development pipeline included 138 active clinical studies, of which 49 were Phase III trials.

In a research tie-up, Cypralis and Gilead Sciences agreed that Cypralis will have exclusive development and commercialization rights to certain macrocyclic inhibitors of peptide bond isomerases, in all fields except for oncology and virology. This follows a multi-year drug discovery collaboration between Selcia Ltd. and Gilead under which Selcia provided drug discovery services to support Gilead’s liver disease research programs. Under the research collaboration, Selcia and Gilead generated four jointly owned patents and two preclinical candidates.

Headcount: 8,900
Revenues: $30,390 (-7%)
Net Income: $13,488 (-26%)
R&D: $5,098 (+69%)

TOP SELLING DRUGS 

Despite having lost a portion of its dominant share in the increasingly competitive Hep C market, Gilead only slipped one slot in this year’s rankings to 8. While the company took a hit financially, with revenues down 7% and earnings down 26%, it was expected, and Gilead’s competitors reaped the rewards.

HCV product sales, which consist of Harvoni, Sovaldi and Epclusa were $14.8 billion for the year, compared to $19.1 billion in 2015. Declines were due to lower sales of Harvoni and Sovaldi, partially offset by sales of Epclusa, which was launched in 2016 in various countries.

R&D expenses, which were up a whopping 69% in 2016, increased primarily due to overall clinical costs, including ongoing milestone payments, and Gilead’s purchase of a U.S. FDA priority review voucher. R&D expenses also include up-front collaboration expenses related to Gilead’s license and collaboration agreement with Galapagos NV, purchase of Nimbus Apollo, Inc. and impairment charges related to IPR&D.

Despite key competition and fewer patients, due to the curative nature of its Hep C products, a large untapped market remains and Gilead has been working to build awareness among an estimated 2.5 million baby boomers in the U.S. If Gilead can maintain its market share in this segment, there is still money to be made.

With its multi-billion dollar HCV franchise, Gilead’s closest competitors remain far behind. Even though Merck, AbbVie, and BMS each have HCV drugs for at least one of the six genotypes, their combined sales don’t touch Gilead’s numbers. Additionally, Gilead’s newest pan-genotype drug Epclusa, approved last June, surpassed its competition in 2016 with $1.8 billion in sales, and it should have a strong hold in the near term.

Epclusa represents the first all-oral, pan-genotypic, single tablet regimen for the treatment genotype 1-6 chronic hepatitis C virus (HCV) infection. It’s also the first single tablet regimen approved for the treatment of patients with HCV genotype 2 and 3, without the need for ribavirin.

Despite high cure rates and simplified treatment for most HCV patients, those who have failed previous treatment with direct acting antivirals continue to represent an unmet medical need. Study results demonstrate that combining three potent antivirals with different mechanisms of action and high barriers to resistance can provide high cure rates for patients who have failed other highly effective oral DAA regimens.

Gilead’s pending SOF/VEL/VOX fixed-dose combination was granted Breakthrough Therapy designation by the U.S. FDA for the treatment of chronic genotype 1 HCV patients who previously failed an NS5A inhibitor-containing regimen.

Additionally, the European Commission approved Gilead’s Vemlidy (Tenofovir Alafenamide, TAF) for the treatment of Chronic Hepatitis B Virus Infection, which is the first new treatment for chronic hepatitis B to be approved in Europe in nearly a decade.TAF is a targeted prodrug of tenofovir that has demonstrated antiviral efficacy similar to Viread, but at one-tenth the dose. TAF is associated with improved renal and bone lab safety parameters compared to TDF in clinical trials.

Vemlidy was approved by the FDA in November 2016 for the treatment of chronic HBV infection in adults with compensated liver disease, and by the Japanese Ministry of Health, Labour and Welfare in December 2016 for the suppression of viral replication in chronic hepatitis B patients with evidence of hepatitis B virus replication and abnormal liver function.

In the near term, Gilead has decent growth potential. Within the next few years. Bictegravir could significantly boost HIV franchise sales. Bictegravir is a combo alternative integrase inhibitor that would come in single tablet form. GSK’s Tivicay has led the market in this space with its HIV segment up 57% in the first quarter, led by Tivicay sales. Gilead stands to recoup some of the market share it lost in this space once Bictegravir hits the market.

Recent trials demonstrated that Gilead’s bictegravir combination could offer an improvement over existing therapies. In four Phase III studies, bictegravir met its primary objective of non-inferiority. Gilead plans to submit a marketing authorization application for BIC/FTC/TAF in the EU in the third quarter of 2017.

Three of the ongoing studies are designed to explore the safety and efficacy of BIC/FTC/TAF compared to triple-therapy regimens containing dolutegravir in treatment-naïve patients and virologically suppressed patients switching from an existing antiretroviral regimen with dolutegravir. A fourth study in virologically suppressed patients compares switching to BIC/FTC/TAF versus remaining on a suppressive regimen of two nucleoside/nucleotide reverse transcriptase inhibitors and protease inhibitor.

Because people with HIV are living longer and are increasingly likely to be taking medication for other conditions, such as heart and liver disease, they are exposed for longer periods of time to the virus and to the medications used to treat it. Therefore, new, effective treatment options are needed that are also tolerable, and offer convenient dosing.

Helping to fulfill this need, Gilead’s once-daily single tablet regimen Odefsey for the treatment of HIV-1 in certain patients, was granted approval in the EU in June 2016, and in the U.S. in March 2016. Odefsey combines Gilead’s emtricitabine and tenofovir alafenamide (marketed as Descovy) with rilpivirine, marketed by Janssen Sciences Ireland UC, a Johnson & Johnson company. Following the approval of Genvoya in November 2015, Odefsey is Gilead’s second STR based on the Descovy backbone to receive marketing authorization in the EU and is currently the smallest pill of any STR for the treatment of HIV.

Additionally, the European Commission approved Gilead’s once-daily Truvada for reducing the risk of sexually acquired HIV-1. This represents the first antiretroviral medicine to be licensed in Europe for pre-exposure prevention, in combination with safer-sex practices, to reduce the risk of HIV-1 in high risk adults.

To maintain its position in the top 10, Gilead needs a new outlet. So far, its oncology efforts have been challenged. Its only approved oncology asset is idelalisib, marketed as Zydelig, which is a second line therapy with boxed warning in three indications: Relapsed chronic lymphocytic leukemia (CLL), in combination with rituximab, in patients for whom rituximab alone would be considered appropriate therapy due to other co-morbidities; Relapsed follicular B-cell non-Hodgkin lymphoma in patients who have received at least two prior therapies; and Relapsed small lymphocytic lymphoma (SLL) in patients who have received at least two prior therapies. Needless to say, Zydelig hasn’t taken off in the oncology sector as anticipated.

Other oncology pipeline assets include: Andecaliximab, an MMP9 inhibitor currently in Phase III trials in gastric cancer, entospletinib, a SYK inhibitor in Phase II in acute myeloid leukemia, and hematopoietic and lymphoid malignancies; and tirabrutinib, a BTK inhibitor in Phase II for B-cell malignancies, as well as couple candidates in early development.

In November, Gilead achieved top-line results from two Phase III trials (SIMPLIFY 1 and 2) that evaluated momelotinib, an investigational inhibitor of Janus kinase (JAK) compared to ruxolitinib or best alternative therapy (BAT) in myelofibrosis, a relatively rare bone marrow cancer. The SIMPLIFY-1 study achieved its pre-specified primary endpoint of non-inferiority to ruxolitinib for splenic response rate, defined as the percentage of patients experiencing a 35% reduction in spleen volume, but SIMPLIFY-2 failed to achieve its primary endpoint of superiority of momelotinib compared to BAT in patients previously treated with ruxolitinib.

In the “other” category, NASH, or nonalcoholic steatohepatitis, is a therapeutic area being pursued by Gilead, and several other drug developers. Allied Market Research estimates that the global market is expected to reach $1.6 billion by 2020. The high prevalence of Type II diabetes and obesity, which leads to NASH and other nonalcoholic fatty liver diseases, has created this market. North America has the highest rates of NASH and other nonalcoholic fatty liver diseases and Europe ranks second in terms of the prevalence.

Results from a Phase II trial evaluating the investigational apoptosis signal-regulating kinase 1 (ASK1) inhibitor selonsertib alone or in combination with the monoclonal antibody simtuzumab (SIM) in NASH and moderate to severe liver fibrosis, demonstrated regression in fibrosis that was, in parallel, associated with reductions in other measures of liver injury in patients treated with selonsertib.

While competition for Gilead’s top franchises took its toll in 2016, HCV and HIV assets moving through the pipeline are likely to put this antiviral authority back on top—remaining there may prove more difficult. A breakthrough product in oncology, cell therapy, or NASH is needed in the long term.

Headcount: 8,000
Revenues: $32,639 (+31%)
Net Income: $18,108 (+50%)
R&D: $3,014 (+6%)

TOP SELLING DRUGS  

Having been referred to as “the Apple of healthcare” another jump for Gilead in the 2015 rankings has the burgeoning biotech up two spots to number 7. While the company’s growth is impressive, driven by staggering Harvoni and Sovaldi sales of $13.9 billion and $5.3 billion, respectively, maintaining this surge within a more crowded Hep C market may prove difficult. Despite pricing pressures and competition for its top Hep C sellers, it still holds a solid 90% market share. Gilead also maintains its dominant position with its growing flagship HIV franchise.

The first quarter of 2016 saw revenues up 3% to $7.8 billion, while net income was down 16% to $3.6 billion due to acquisition-related, up-front collaboration, stock-based compensation expenses, as well as reflecting lower revenues in the Hep C arena. Antiviral product sales, which include HIV and liver disease areas, were $7.2 billion, up 3%. Truvada sales were up 16% to $898 million, Atripla sales declined 8% to $675 million due to patent expirations, and Stribild sales were up 34% to $477 million. While Harvoni sales slipped 16% in the first quarter, Sovaldi sales were up 31%.

The Hep C market saw a significant drop in prices as a result of the launch of Merck’s Zepatier in January, which considerably undercut both AbbVie’s Viekira Pak and Gilead’s Harvoni on price—not to mention this strategy could give payers the leverage needed to negotiate even further discounts. Viekira Pak launched in December 2014, just two months after Harvoni was approved, and exclusive deals with insurers to cover the drug in return for discounts quickly ensued. Gilead was forced to do the same, impacting 1Q16 sales.

Compared to its closest competitors, AbbVie, Merck, and Celgene, Gilead’s financials and assets appear in good working order, and its pipeline comprises several late-stage product candidates for high value indications, namely cancer, heart disease, and HIV. While these candidates are not likely to have the financial impact of Harvoni and Sovaldi, they’re diversified and have the potential to replace some of the lost revenue in the Hep C arena, which, due to the curative nature of these therapies, is not likely to be able to support multiple blockbusters long term.

Additions to Gilead’s HIV therapies include the FDA approval of Odefsey (emtricitabine /rilpivirine /tenofovir alafenamide or R/F/TAF) for the treatment of HIV-1 infection. Odefsey is Gilead’s second TAF-based regimen to win FDA approval and represents the smallest pill of any single-tablet regimen currently available for the treatment of HIV. The drug will likely gain EU approval as well, with the European CHMP adopting a Positive Opinion for Odefsey this past April. Emtricitabine and tenofovir alafenamide are from Gilead, while rilpivirine is from Janssen Sciences Ireland.

The European Medicines Agency (EMA) also adopted a positive opinion for two doses of Descovy (emtricitabine 200 mg/tenofovir alafenamide 25 mg, F/TAF), an investigational fixed-dose combination for the treatment of HIV-1 in combination with other antiretroviral agents.

Antiviral asset bictegravir (GS-9883), an investigational integrase strand transfer inhibitor achieved proof-of-concept based on data from four preclinical and Phase I studies evaluating the antiviral potency, resistance profile, pharmacokinetics and safety. Bictegravir, including in combination with tenofovir alafenamide and emtricitabine as a single tablet regimen, is an investigational treatment for HIV currently in Phase III trials as part of the single tablet regimen.

In HCV, Harvoni picked up two supplemental indications for use in chronic hepatitis C patients with advanced liver disease. Also, the FDA granted priority review to the company’s NDA for an investigational once-daily fixed-dose combination of sofosbuvir and velpatasvir (SOF/VEL) for the treatment of chronic genotype 1-6 HCV infection. The FDA has set a target action date under the Prescription Drug User Fee Act of June 28, 2016.

Finally, while Gilead terminated its Phase II study of the investigational monoclonal antibody simtuzumab in patients with idiopathic pulmonary fibrosis (IPF) due to lack of efficacy, Phase II studies of simtuzumab are ongoing in patients with non-alcoholic steatohepatitis (NASH) and primary sclerosing cholangitis (PSC).

In addition to these pipeline assets, several noteworthy acquisitions and collaborations broadened Gilead’s portfolio. Most recently, the company acquired Nimbus Apollo and its Acetyl-CoA Carboxylase (ACC) inhibitor program for $400 million upfront, and an additional $800 million in development milestones. The Nimbus Apollo program includes the lead candidate NDI-010976, an ACC inhibitor, and other preclinical ACC inhibitors for the treatment of NASH, and for the potential treatment of hepatocellular carcinoma (HCC) and other diseases. NDI-010976 was Fast Tracked by the FDA in February 2016 and Phase I data for the compound is expected to be available soon.

Gilead also acquired EpiTherapeutics, a privately-held Danish company, for $65 million, gaining a portfolio of histone demethylases for the treatment of certain cancers.

Finally, Galapagos and Gilead Sciences completed the closing of their global license and collaboration agreement on filgotinib, triggering an upfront license fee payment of $300 million to Galapagos. Gilead has also made a $425 million equity investment in Galapagos and now owns 14.75% of its outstanding shares.

The companies entered a collaboration for the joint development and commercialization of filgotinib in inflammatory diseases in December 2015. Galapagos co-funds 20% of global development activities and Gilead is responsible for manufacturing and worldwide marketing and sales activities.

A Phase III program with filgotinib in rheumatoid arthritis will be initiated mid-2016. Filgotinib has also been shown to be safe and effective in moderate to severe Crohn’s disease, based on Phase II study results.

In executive news, as of March 2016, John C. Martin, Ph.D., chairman and chief executive officer of Gilead stepped down, assuming the role of executive chairman of the company. John F. Milligan, Ph.D., was promoted to CEO and will serve on the board of directors. Dr. Martin joined the company in 1990 and served as CEO since 1996. Dr. Milligan also joined Gilead in 1990 and most recently served as president and chief operating officer. Under Martin, Gilead grew from a small biotech worth $1 billion, to a top 10 biopharma company bringing in nearly $33 billion in 2015. If Dr. Milligan can keep pace in today’s challenging environment, Gilead’s outlook is strong.

Headcount: 7,000
Revenues: $24,890 (+127%)
Net Income: $12,059 (+294%)
R&D: $2,85 4(+35%)

TOP SELLING DRUGS

In today’s sluggish R&D environment, Gilead is surpassing the odds—and its anti-viral competition—with burgeoning Solvaldi and Harvoni sales and flagship HIV franchise. Solvaldi alone nearly matched the company’s net revenues in 2013, with an astounding $10.3 billion in sales in 2014. No one is putting up numbers and results quite like this biotech behemoth, which jumped from 19 in last year’s ranking, to nine, joining the likes of Lilly and AstraZeneca.

Sovaldi, which was approved in the U.S. and EU in December 2013 and January 2014, respectively, proved a valuable advance for hepatitis C-related liver disease, providing the first cure for the virus. It’s now approved in more than 40 countries, and more than 170,000 HCV patients have been treated with a Sovaldi-containing regimen since the product was launched. However, more in-house—and to a lesser extent—external competition has sales cooling. Abbvie’s Viekira (approved December 2014) hasn’t made quite the financial impact as Sovaldi—at least not yet. It debuted with $48 million in sales in 2014, and jumped to $231 million in 1Q15.

More significantly, in Gilead’s efforts to further convenience and reduce treatment duration (and remain competitive), Harvoni was approved in the U.S., Canada, the EU and Switzerland in 2014, and debuted at $2.1 billion in sales for the year (and a whopping $3.6 billion in 1Q15). It’s the first once-daily single-tablet regimen (STR) to treat chronic HCV in genotype 1 patients–the most prevalent worldwide. Building on Sovaldi’s success, Harvoni eliminates the need for both interferon and ribavirin, and in clinical trials provided cure rates of 94–99% in as few as eight weeks. However, its introduction hit Sovaldi sales, which were down 57% to $972 million in 1Q15.

Sovaldi has made headlines this past year due to its price tag. In the U.S., the cost for the cure is $63,000 to $94,500, depending upon the drug and regimen, before any discounts. On an infamous note, Senator Bernie Sanders of  VT is demanding the Government override Gilead’s patents in a rash effort to get meds to veterans. Perhaps there’s a better way?

In January, Gilead expanded its hep C generic manufacturing licensing agreements with India-based partners to include the investigational GS-5816, in Phase III studies as part of a single tablet regimen in combination with sofosbuvir for the treatment of all six genotypes of hepatitis C. This would allow the manufacture and distribution in 91 developing countries, which account for 54% of the total worldwide HCV population. If approved, the regimen would become the first pan-genotypic, all-oral single tablet regimen for HCV.

Gilead also picked up Phenex Pharmaceuticals’ Farnesoid X Receptor (FXR) program for $65 million, which includes small molecule FXR agonists being explored to treat of liver diseases, including nonalcoholic steatohepatitis (NASH), which is a common, serious chronic liver disease affecting 10 to 20% of people in the developed world, and for which there are currently no

approved therapies.

While the flagship HIV franchise faces several significant patent expiries, the company continues to develop new treatment regimens to thwart the impact of looming expiries. This common pharma practice may pay off in the short term, but Gilead will need to continue to address evolving needs and treatment options for the disease.

The company has made progress with regimens containing tenofovir alafenamide (TAF), demonstrating high antiviral efficacy and an improved safety profile. Results from two Phase III studies showed the compound known as E/C/F/TAF (elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide) had more favorable renal and bone safety profiles compared with Stribild.

Gilead also expanded its partnership with Janssen R&D Ireland, its distribution partner for Complera/Eviplera, to include the development and commercialization of R/F/TAF, which is F/TAF plus Janssen’s rilpivirine. Several Phase I and II studies of the new STR have been completed, and if approved, would be the first protease inhibitor-based STR.

Gilead’s oncology efforts don’t hold quite the same revel at its anti-viral successes. Fledgling, Zydelig, a PI3K delta inhibitor approved in the U.S. and EU in 2014 for several blood cancers, brought in a mere $23 million in sales. Zydelig is the company’s foremost foundation from which to develop new cancer therapies, including combination regimens to achieve better and more durable response rates and to expand the number of cancer indications. The drug has also shown potential benefit in a variety of lymphomas at various stages.

Gilead acquired EpiTherapeutics ApS, a privately-held Danish company, for $65 million. EpiTherapeutics has a library of first-in-class, selective small molecule inhibitors of epigenetic regulation of gene transcription, in particular histone demethylases. The company’s lead preclinical compounds are being studied for the treatment of certain cancers.

The company’s oncology pipeline includes GS-4059, a BTK inhibitor recently licensed from Ono Pharmaceutical, for the treatment of B-cell malignancies and other diseases. Gilead now has compounds targeting several signaling pathways associated with B-cell malignancies–PI3K delta, Syk, JAK and BTK. There’s also the recently acquired EpiTherapeutics portfolio of preclinical histone demethylases for certain cancers, which falls into the company’s combination strategy.

Several other focus areas include three clinical stage compounds for ulcerative colitis and Crohn’s disease, rare and potentially fatal heart conditions, respiratory syncytial virus (RSV), and idiopathic pulmonary fibrosis.

With impressive earnings growth and growth potential, this outperforming innovator doesn’t show any signs of weakness, and is expected to continue to dominate the HIV and hep C markets in the near-term.

Well, Gilead Sciences has definitely been the company that has galloped up the charts this year moving from 19th last year up into the Top 10 for 2015. The company, which has historically focused on HIV has been rocketed into the ether by souring sales of its latest hepatitis C drug, Harvoni (ledipasvir/sorosbuvir) accompanied by the very slightly older brother Solvadi. Solvadi was licensed by the FDA and in the EU in early 2014 followed by Harvoni in 4Q. While Solvadi is the less user friendly of the two drugs and has suffered at the appearance on the market of Harvoni, all of the company’s expectations have been surpassed, and as a result has increased its expected sales in 2015 by a billion dollars.

Even though Gilead has competition hot on its heels from AbbVie and Merck, its drugs provide an effective cure for the disease. Even the somewhat hefty price tag of $1,000 a day makes it cost effective in the long term.

Gilead is not resting on its laurels though. The drug pipeline for Gilead is strong with further regulatory submissions in place in the U.S. and EU in HIV therapy, and with late stage trials in liver disease and oncology, Gilead looks to be a strong player and a force to be reckoned with in the starry heights of the Global Top 10. Having realized strong sales results for the start of this year, it will be interesting to see how the coming months pan out and where it will send them in 2016.

—Adele Graham-King

Headcount: 6,000
Pharma Reveneus: $10,803 (15%)
Total Revenues: $11,201 (15%)
Net Income: $3,074 (19%)
R&D Budget: $2,119 (20%)

Top Selling Drugs  

Its extremely profitable HIV franchise remains the main driver of Gilead’s financial success and its backbone for long-term revenue. For the last 10 years, it has dominated 90% of the market for newly diagnosed patients, with Viread and Emtriva as the first-line treatment. The company also markets Atripla, the first once-daily single-pill regimen, which is a co-formulation of these two drugs, along with Bristol-Myers Squibb’s Sustiva, and is its top seller. Also noteworthy, sales for the one tablet combo pill Stribild (elvitegravir, cobicistat, tenofovir, and emtricitabine), soared 837%. All in all, more than 72% of all HIV patients take at least one of the company’s drugs. Adding to the franchise, Vitekta tablets gained marketing authorization in the EU for HIV-1 infection in adults with resistance to elvitegravir.

Gilead and AbbVie’s recent roll out of the first interferon-free treatment for HCV 1, Sovaldi has become a runaway success, with Gilead fast becoming a leader in the Hep C market. Moreover, Thomson Reuters IP & Science business forecasting declared Sovaldi, along with Gilead’s Idelalisib, among the three most promising drugs to launch in 2014 (the third is GlaxoSmithKline’s Anoro Ellipta). However, it turns out that they had grossly underestimated Sovaldi’s potential, expecting more than $1 billion in sales through 2019. Sovaldi, which launched in December 2013, reached a staggering $2.3 billion in 1Q14 following the January launch in Europe. Treatment cost is high at around $84,000, but treatment time has dropped from 48 to 12 weeks.

The company is also investigating all-oral regimens containing sofosbuvir (Sovaldi) for chronic HCV infection, and in April received Priority Review Designation from the FDA for Ledipasvir/Sofosbuvir Fixed-Dose Combination Tablet. These results demonstrated curative potential, as it was shown to be effective across all genotypes and patient subgroups.

In oncology, Gilead is researching three distinct pathways associated with cancer with three drugs: idelalisib, GS-9973, and momelotinib. Of these promising candidates, idelalisib, an oral inhibitor of PI3K delta, now has pending applications in the U.S. and EU in indolent non-Hodgkin’s lymphoma (iNHL), with studies demonstrating an overall response rate of 57%, and 71 patients responding to the therapy. Futhermore, Gilead stopped a Phase III idelalisib study in chronic lymphocytic leukemia (CLL) based on interim analysis showing highly significant efficacy for the primary endpoint of progression-free survival. In line with these findings, the FDA granted a Breakthrough Therapy designation for idelalisib in CLL.

Also in CLL, most recent interim results of a Phase II study evaluating GS-9973, an investigational oral inhibitor of spleen tyrosine kinase (Syk), achieved an overall response rate of 49%, with an estimated progression-free survival rate of 70%, and 62% of patients achieved at least a 50% tumor reduction. Meanwhile, Momelotinib, a JAK inhibitor, has progressed to Phase III development in Myelofibrosis, and is also being studied in pancreatic cancer.

The pipeline is also fostering some promising mid-stage candidates in the areas of anti-viral and cardiovascular therapies. Phase II results of GS-5806, an investigational oral RSV fusion inhibitor in respiratory syncytial virus (RSV), achieved its primary and secondary endpoints of lower viral load and improvement in symptoms.

A Phase II study evaluating ranolazine and low-dose dronedarone in atrial fibrillation showed that the combination regimen provided greater reductions in AF than either therapy alone. Ranolazine is currently approved in the U.S. as Ranexa for the treatment of chronic angina.

Headcount: 5,000
Pharma Revenues: $9,398 (16%)
Total Revenues: $9,703 (16%)
Net Income: $2,592 (-8%)
R&D Budget: $1,760 (43%)

Top Selling Drugs

Account for 98% of total pharma sales, same as in 2011

Headcount: 4,000
Pharma Revenues: $7,390 (14%)
Total Revenues: $7,949 (13%)
Net Income: $2,890 (10%)
R&D Budget: $1,073 (14%)

Top-Selling Drugs in 2010

Account for 99% of total pharma sales, same as in 2009.

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