Headcount: 15,883
Revenues: $11,338 (-4%)
Net Income: $1,905 (-4%)
R&D: $2,037 (0%)

TOP SELLING DRUGS

Astella’s revenue in fiscal year 2020 decreased 4% to $11.3 billion, mainly due to the loss of market exclusivity of Vesicare for the treatment of overactive bladder in Europe, and the termination of sales agreements for Symbicort for asthma, human vaccines of KM Biologics Co., Ltd., Micardis family for the treatment of hypertension, and Celecox for the treatment of inflammation and pain in Japan.

Despite the challenges of 2020, sales of main products XTANDI for the treatment of prostate cancer and XOSPATA for the treatment of acute myeloid leukemia continued to grow. In addition, growth of the co-promotion revenue of PADCEV for the treatment of urothelial cancer contributed to revenue. Moreover, sales of Betanis / Myrbetriq / BETMIGA for the treatment of OAB showed steady progress, and new product groups in Japan achieved sales growth, including those of EVENITY for the treatment of osteoporosis, Suglat and SUJANU Combination Tablets for the treatment of diabetes mellitus.

In pipeline news, the company submitted an application in the U.S. in December 2020 for immunosuppressant agent Prograf for an additional indication of prevention of rejection in lung transplantation. In March 2021, the company obtained the approval of a new oral extended-release formulation and existing tablets for the additional indication of neurogenic detrusor overactivity in children aged three years and older for the OAB treatment Myrbetriq in the U.S.

In 2018, Astellas adopted an approach called “Focus Area Approach” as its research and development strategy. As of March 2021, it has selected four Primary Focuses: “Blindness & Regeneration,” “Mitochondria Biology,” “Genetic Regulation,” and “Immuno-Oncology.”

In January 2020, Astellas acquired Audentes Therapeutics, Inc, and gained capabilities for gene therapy, including technology platforms and manufacturing capabilities to develop new drug candidates into clinical stage. By obtaining these assets, Astellas has made a significant first step toward becoming a front runner in this area. In April 2021, it reorganized the Audentes Division to establish a research and manufacturing division, a development division, and a commercial division that will specialize in the area of gene therapy.

In September 2020, the company initiated a joint research collaboration with the University of Pittsburgh in gene therapy using Adeno-associated viruses to create development candidates for the treatment of dry age-related macular degeneration. Also in September, the company signed an agreement with the University of Tokyo’s Center of Innovation on collaborative efforts to create innovative new drugs and medical solutions.

In December 2020, Astellas entered into an exclusive worldwide license agreement with KaliVir Immunotherapeutics LLC for the collaboration, development and commercialization of VET2-L2, an intravenously administered oncolytic virus, as well as a second, follow-on development candidate.

In January 2021, the Kyushu Distribution Center, the company’s fourth distribution base in Japan, began operations in Kitakyushu City. Furthermore, Astellas began construction on a new sterile drug production line in the Yaizu Technology Center of Astellas Pharma Tech Co., Ltd., a manufacturing subsidiary of the company.

Headcount: 15,883
Revenues: $11,927 (+1%)
Net Income: $1,798 (-20%)
R&D: $2,079 (+1%)

Top Selling Drugs

Headcount: 16,243
Revenues: $11,781 (flat)
Net Income: $2,249 (+22%)
R&D: $1,882 (-6%)

Top Selling Drugs

Astellas reported flat revenues of $11.7 billion for 2018. It’s prostate cancer drug Xtandi was again its top seller with $3 billion in sales, up 13%, while development is ongoing to expand the indication to earlier stages of prostate cancer.

The year kicked off for Astellas closing its $450 million purchase of Mitobridge at the end of January 2018. At the time, the two companies had an existing R&D collaboration in place focused on developing drugs that target mitochondrial function. These drug candidates have the potential to treat genetic, metabolic or neurodegenerative disorders as well as conditions of aging. MA-0211, the most advanced program emerging from the collaboration, was in Phase 1 studies for Duchenne Muscular Dystrophy (DMD).

The year continued with the Japanese pharma major on the acquisition hunt and bolstering its cell and gene therapy capabilities. It acquired Universal Cells, gaining the proprietary Universal Donor Cell technology to create cell therapy products that do not require Human Leukocyte Antigen (HLA) matching, potentially overcoming a huge treatment challenge by reducing the risk of rejection.

Next, Astellas inked a deal for UK-based gene therapy company Quethera, which is focused on developing novel treatments for ocular disorders. Astellas gains Quethera’s ophthalmic gene therapy program, which uses a recombinant adeno-associated viral vector system (rAAV) to introduce therapeutic genes into target retinal cells for the treatment of glaucoma.

At the end of the year, Astellas purchased Potenza Therapeutics following the successful outcome of a collaboration agreement to build a portfolio of novel immuno-oncology (IO) therapies. The clinical IO therapies developed may also provide a platform for IO combinations with Astellas’ existing non-IO programs for life cycle management and future novel IO combinations. Together the companies discovered and developed three investigational new drugs (INDs) with the potential to treat various cancers that are non-responsive or resistant to the current generation of IO therapies. These programs target immune stimulation, immune checkpoint inhibition, and regulatory T cell function and include: ASP8374/PTZ-201, an anti-TIGIT antibody and ASP1948/PTZ-329, an anti-NRP1 antibody, both of which are currently in Phase I studies; and ASP1951/PTZ-522, a novel format GITR agonistic antibody, which has achieved IND clearance.

During the year, Astellas expanded its cell and gene therapy infrastructure on three fronts, beginning construction of new research, development and manufacturing facilities, in Japan and the U.S. The Center for Active Ingredient for Biopharmaceuticals will be built at the Toyama Technology Center of Astellas Pharma Tech, a production subsidiary of Astellas. It will be capable of manufacturing antibodies for use in both clinical trial materials and commercial products, while also manufacturing products that include other modalities such as cell therapy. The new Center for Multimodality CTM, at the Tsukuba Biotechnology Research Center of Astellas in Japan, will be responsibile for the manufacture of CTM for use in early-stage clinical trials designed for the purpose of developing cell therapies and gene therapies for patients in Japan, U.S. and Europe. Lastly, the Astellas Institute for Regenerative Medicine, a center of the R&D of regenerative medicine and cell therapy located in Massachusetts, will move to a new location within the state and will be upgraded.

Headcount: 16,617
Revenues: $12,238 (-1%)
Net Income: $1,836 (-4%)
R&D: $1,984 (+6%)

Top Selling Drugs  

This year was fruitful in the area of acquisitions for Astellas Pharma, with the company rounding out December 2017 with an agreement to acquire Mitobridge for an upfront fee of $225 million. Mitobridge will also be eligible for additional payments that total up to $225 million, depending on the progress of various programs in clinical development. Before the $450 million dollar deal was inked, the two companies had an existing R&D collaboration in place focused on discovering and developing novel drugs that target mitochondrial function. These drug candidates have the potential to treat genetic, metabolic or neurodegenerative disorders as well as conditions of aging. MA-0211, the most advanced program emerging from the collaboration, is currently in Phase I trials for Duchenne Muscular Dystrophy (DMD). In another acquisition, Astellas bought Universal Cells in February 2018 for an upfront payment of $102.5 million plus milestones. Through that deal, Astellas gains Universal Cells’ proprietary Universal Donor Cell technology to create cell therapy products that do not require Human Leukocyte Antigen (HLA) matching, potentially overcoming a huge treatment challenge by reducing the risk of rejection.

While Astellas did not have any major approvals during the year, they are expected soon. In late May 2018, the FDA accepted the company’s New Drug Application (NDA) for Priority Review for gilteritinib, for the treatment of adult patients who have relapsed or refractory Acute Myeloid Leukemia (AML) with a FLT3 mutation. Previously, gilteritinib was granted both Orphan Drug designation and Fast Track designation by the U.S. FDA and the European Commission. Additionally, in a collaboration with Pfizer, in September 2017 Astellas announced positive top-line results of the Phase III PROSPER trial evaluating XTANDI for the treatment of Castration-Resistant Prostate Cancer, and in March 2018, XTANDI Tablets in 40 mg and 80 mg dosage received manufacturing and marketing approval in Japan for the same indication. Also in September, the FDA accepted a supplemental New Drug Application for review that seeks approval for the use of mirabegron in combination with solifenacin succinate 5 mg for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency. That submission is based on positive data from the global Phase III SYNERGY I, SYNERGY II and BESIDE studies.

Astellas was very active in partnerships and collaborations during the year. In collaboration with Seattle Genetics, Inc., Astellas was granted Breakthrough Therapy Designation in March 2018 by the FDA for enfortumab vedotin, an antibody-drug conjugate (ADC), for locally advanced or metastatic urothelial cancer who were previously treated with checkpoint inhibitors (CPI).  Also, in March, Actinium Pharmaceuticals entered into research and option agreement with Astellas to develop Actinium-225 Radio-Conjugates (ARCs) using its Actinium Warhead Enabling (AWE) Platform Technology. Under this collaboration, Actinium will utilize its AWE Platform to conjugate and label selected Astellas targeting agents with the actinium-225 (225Ac) payload. Actinium will also be responsible for conducting preclinical validation studies on the novel ARCs generated. Actinium will receive a seven-digit payment, which includes upfront fee and research funding from Astellas.

Headcount: 17,454
Pharma Reveneus: $11,086 (16%)
Total Revenues: $11,086 (16%)
Net Income: $884 (-2%)
R&D Budget: $1,862 )20%)

TOP SELLING DRUGS

Astellas, Japan’s second largest pharma company based on revenues, maintains its post. While still overcoming the patent cliff for certain mainstay products, namely Lipitor, Prograf sales remain steady despite generic competition, flagship product sales were steady, and several promising advances in its pipeline hold potential.

It was a big year for Astellas’ oncology efforts with the launch of XTANDI for the treatment of prostate cancer in the U.S. and subsequent launch in the UK in July 2013, marking a major milestone in establishing an oncology franchise, behind urology and transplantation. XTANDI, with sales reaching an impressive $531 million for the fiscal year, is well positioned to grab the market share from J&J’s Zytiga, which had $1.7 billion in 2013 sales. Further success appears to be imminent, as Astellas and its development partner, Medivation, have pending indications, including earlier-stage prostate cancer and treatment naïve patients, with the EU recently recommending approval, and the FDA granting Priority Review designation.

Launched in FY12, overactive bladder (OAB) treatment Myrbetriq is the driving force behind the company’s urology franchise, with sales reaching $274.3 million in FY13, up 306%. Using a distinct mechanism of action versus anticholinergics, such as Vesicare, Myrbetriq is fast becoming another treatment option. Vesicare also performed well, with sale up 24% in the Americas, 42% in Europe, 30% in Asia and Oceania, and in Japan expanded steadily, up 3%. The company continues to tap into the OAB treatment market by raising public awareness of the condition, despite the ongoing gradual decline in the OAB market size.

In addition to stable growth in transplantation, flagship Prograf saw steady sales increases for treating autoimmune diseases, including rheumatoid arthritis (RA), lupus nephritis, myasthenia gravis, and ulcerative colitis. The RA indication now accounts for nearly half of Prograf sales in Japan. Although sales in the Americas were down 6%, sales in Europe were up 24%, and the once-daily formulation Advagraf, was up 35%, while Asia and Oceania and Japan sales were up 32% and 2%, respectively.

In its pursuit of sustainable growth, the company has taken on a series of initiatives to transform its business structure, resulting in several organizational and personnel changes. Measures to reform its research framework include closing its Kashima facility in Osaka in fiscal 2015, and closing or scaling back research units in the U.S., including OSI Pharmaceuticals and Astellas Research Institute of America.

Instead, Astellas is investing in the recently established a Regenerative Medicine Unit that will specialize in a research platform for regenerative medicine and cell therapies, as well as the Astellas Innovation Management (AIM), established to enhance and accelerate the process of screening and acquiring external opportunities during preclinical development. Additionally, based on a series of recent management decisions, Astellas transferred its fermentation research-related assets to Taiho Pharmaceutical, reallocating those R&D resources with the goal of generating innovative drugs.

Also part of ongoing efforts to achieve operational excellence, Astellas inked an agreement with Accenture for the business process outsourcing of multiple business areas and its domestic subsidiaries. And, this past February, reorganized its top management structure, deciding that all heads of global development, regulatory affairs, clinical and research quality assurance, will now report to the chief medical officer.

In the way of pipeline progress, Astellas’ SGLT2 inhibitor Suglat Tablets became available for type 2 diabetes in Japan in April. Suglat, discovered through a research collaboration with Kotobuki Pharmaceutical, reduces blood glucose levels by inhibiting SGLT2 and the reuptake of glucose—the first of its kind approved for type 2 diabetes in Japan.

Astellas and FibroGen initiated a Phase II study of ASP1517/FG-4592 for the treatment of anemia associated with chronic kidney disease (CKD) in patients on dialysis. This orally administered small molecule inhibitor of hypoxia-inducible factor prolyl hydroxylase (HIF-PHI), is among the most clinically advanced candidate in this new class of potential anemia therapies.

Additionally, Astellas and Vical initiated a Phase III trial of ASP0113 (TransVax) in approximately 500 hematopoietic cell transplant (HCT) recipients, making it the first investigational Cytomegalovirus (CMV) vaccine to reach Phase III testing. It’s also being studied in solid organ transplant recipients.

Among several notable collaborative efforts, Astellas and ClearPath entered a strategic pact to form a portfolio of development companies focused on vaccines that target infectious diseases. This partnership supports Astellas’ goal of building a global vaccine franchise and the launch of its first company, RSV Corp. in December 2013, which will fund the development of a virosome vaccine technology licensed from Mymetics Corp. for respiratory syncytial virus (RSV).

Other R&D ventures include collaborations with Mitokyne, focused on developing drugs that improve mitochondrial functions to potentially treat genetic, metabolic or neurodegenerative disorders, as well as conditions of aging, and another with Cytokinetics for the development of skeletal muscle activators for diseases and medical conditions associated with muscle weakness.

With these agreements, Astellas has the exclusive right to acquire Mitokyne during the term of their five–year agreement. Including upfront, R&D funding, acquisition and milestone payments, the total value of the partnership could reach as much as $730 million. In the Cytokinetics alliance, Astellas will have the exclusive rights to develop and commercialize drug candidates, including CK-2127107, a fast skeletal troponin activator drug currently in Phase II trials.

So far, the company’s 2014 mid-term management plan, dating back to 2010, has accomplished several milestones related to therapeutic and R&D innovation aspirations. Gaining approval of XTANDI certainly places them closer to their oncology category leader goal. Additionally, should several key portfolio assets meet with success, Astellas might achieve its plan to become a global category leader in immunology and infectious disease, neuroscience, diabetes complications, and kidney disease.

Headcount: 17,454
Pharma Revenue: $12,168 (-1%)
Total Revenues: $12,168 (-1%)
Net Income: $1,00 (21%)
R&D Budget: $2,202 (-9%)

Top Selling Drugs

Account for 52% of total pharma sales, down from 54% in 2011

Astellas maintains a stronghold through its transplantation/immunology and urology franchises. With only mild declines, its immunosuppressant Prograf continues to provide steady revenues despite generic competition in the U.S. Part of the reason is that these drugs are often taken long-term and generics are not as sought after in transplantation as with other therapeutic areas. In Europe, Prograf sales are steady thanks to an exclusive once-daily injectable, while continued sales growth is expected in Japan and Asia. In the meantime, Astellas has several clinical-stage drug candidates in clinical development, including ASP015K (to treat rheumatoid arthritis, etc.), ASKP1240 (prevention of organ transplant rejection), and Diannexin (prevention of delayed graft function in kidney transplantation).

In the overactive bladder space (OAB), Vesicare is the leading treatment in Japan, the U.S., and Europe. Thwarting impending declines with Vesicare’s first patent expiry in 2015, newly approved Myrbetriq, which offers a different mechanism of action to treat OAB, will likely pick up any slack. Myrbetriq became available in the U.S. in late October 2012. This should provide plenty of time to implement its strategy of launching a new-generation drug to supplement the one heading toward expiry, and moving patients over to the newer therapy.

As parts of its 2014 MTP strategy, Astellas is striving to become a global category leader in a third therapeutic area, oncology. A step towards realizing this goal comes with the September 2012 FDA approval of XTANDI (enzalutamide), an androgen receptor inhibitor for the treatment of prostate cancer (developed in partnership with Medivation). On the not-so-bright side, this past May, the FDA Oncologic Drugs Advisory Committee (ODAC) voted that the application for tivozanib did not demonstrate a favorable benefit/risk profile for the treatment of advanced renal cell carcinoma (RCC). While the FDA is not bound by the Committee’s guidance, its input will be considered in the review of the tivozanib, which is expected in late July.

Other oncologic efforts include the recent partnership with Ambrx for the discovery and development of novel antibody drug conjugates (ADCs), which allow for the targeted delivery of drugs. Astellas paid $15 million upfront, and will pay as much as $285 million in research, development, regulatory and sales milestones for an undisclosed number of oncology targets, which Astellas would have worldwide rights to develop and commercialize.

In May, president and CEO, Yoshihiko Hatanaka, announced plans to restructure its R&D framework. Initiatives include utilizing more external capabilities and resources, undertaking new therapeutic areas and technologies, including regenerative medicine and vaccines, and ensuring sufficient late-stage pipeline investment. Through the establishment of Astellas Innovation Management (AIM), the company aims to enhance external opportunities during the preclinical development stage, and consolidate research functions. These initiatives, scheduled during FY2013, involve reallocating resources by closing and scaling back U.S.-based research functions, some of which will transfer to the Tsukuba Research Center. OSI Pharmaceuticals will be closed, along with Perseid Therapeutics. Astellas Research Institute of America LLC will be scaled back to focus on CNS therapies. The losses related to these initiatives are approximately JPY 11 billion have been accounted for in the FY14 forecast.

As a strictly innovative drug firm, the company prides itself on its drug discovery capabilities and development portfolio, as well as a well-balanced business platform. If its OAB strategy works, Myrbetriq will make up for any losses Vesicare may suffer under pending expiry, steadying revenues as other oncology initiatives ranging from early to late-stage development candidates, progress.

Headcount: 15,161
Pharma Revenues: $11,161 (6%/-2%*)
Total Revenues: $11,161 (6%/-2%*)
Net Income: $792 (-40%/-45%*)
R&D Budget: $2,543 (21%/11%*)

* Converted at avg. exch. rate / based on reported currency (JPY)

Top-Selling Drugs in 2010

Account for 56% of total pharma sales, down from 62% in 2009.

PROFILE

Astellas’ mid-term management plan, “MTP14,” aimed at accelerating growth from April 2010 to March 2015 with the goal of achieving $13.6 billion in annual revenues by 2014, fell short of performance targets in its debut year. Currency fluctuation, delayed product launches, “worse than expected” generic challenges and mounting competition for the company’s mainstay products — transplant drug Prograf, Harnal for BPH, and Vesicare for overactive bladder — waylaid the ambitious plan.

In its efforts to respond to recent challenges, the company plans to grow its urology franchise with overactive bladder (OAB) drugs Vesicare and mirabegron, with product launches expected in the MTP14 timeframe. Astellas is counting on benefiting from what it deems as a huge, untapped OAB market. In the year ended March 2010, OAB sales topped $1.0 billion, a figure the company expects to double by 2014. Mirabegron gained approval in Japan in June 2010. Additionally, Astellas exercised its right under an agreement with co-promotion partner GlaxoSmithKline to assume full commercial responsibility in the U.S. for Vesicare. Astellas will make payments to GSK until 2015, when the original agreement expires.

Any successors to Astellas’ former bestseller transplantation drug Prograf are in pre-proof-of-concept stage, so we’re not likely to see any product launches in this arena within the MTP14 timeline. Under an agreement with Alavita, Astellas has an exclusive option to acquire all assets relating to Diannexin, currently in Phase II development to prevent delayed graft function in kidney transplantation. Astellas also signed a strategic equity deal with Cytori Therapeutics to evaluate regenerative cell drug technology and extended its VelocImmune Antibody Technology license with Regeneron through 2023 in its efforts to discover human monoclonal
antibody product candidates.

In addition to urology and transplantation, Astellas has ambitions in oncology. Thanks to some additions from the OSI Pharmaceuticals merger last year, three product launches are anticipated closer to 2015: degarelix for advanced prostate cancer, AC220 for AML, and MDV3100 for prostate cancer.

Astellas also partnered with Aveo Pharmaceuticals to commercialize Aveo’s lead oncology drug tivozanib for all markets outside of Asia. Tivozanib is currently in Phase III testing for the treatment of kidney cancer. If approved, the two companies will share profits in North America and EU.

Fortunately, in Astellas’ latest update of disaster-affected facilities following the March 2011 earthquake, tsunami and meltdown, the company reported that all employees at Process Chemistry Labs and Astellas Pharma Tech have returned to work, and restoration of manufacturing facilities is progressing, with production expected to recommence in October.
Process Chemistry Labs manufactures the drug substances of Harnal, Bonoteo, and other products. Adequate inventories of core products allowed for uninterrupted supply. Astellas estimates the total cost of repairs and costs from suspended operations amount to approximately $56.0 million.

Astellas’ OAB ambitions are promising; if they pan out, they could buy enough time for some oncology approvals, and perhaps a Prograf successor, positioning the company on par with growth expectations.  —KB

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Headcount: 14,261
Pharma Revenues: $10,509 (+9%/-1%)
Total Revenues: $10,509 (+9%/-1%)
Net Income: $1,318 (-23%/-28%)
R&D Budget: $2,108 (+33%/+23%)

Revenues converted at average exchange rate / based on reported currency (JPY)

Account for 62% of total pharma sales, same as in 2008.

PROFILE

Thanks to the mergers of 2009, Astellas has moved up in the ranks from its #18 position last year. The company has professed its strategy to become a global leader in oncology, and its goal is that much closer to being realized after it closed its $4 billion acquisition of OSI Pharmaceuticals in June 2010. OSI manufactures and sells Tarceva, a leading cancer drug, and has several prospective new oncology medications in its pipeline. OSI’s revenues for 2009 totaled $428 million with an operating income of $153 million.

In support of its oncology ambitions, Astellas partnered with Ambit Biosciences to develop and commercialize FLT3 kinase inhibitors in oncology and other indications. The partnership includes AC220, Ambit’s lead investigational drug in Phase II trials in acute myeloid leukemia (AML). Additionally, Astellas and Medivation, Inc. entered a global agreement to develop and commercialize MDV3100, Medivation’s investigational drug for the treatment of prostate cancer, which is currently being evaluated in a Phase III trial.

Astellas’ franchises in urology and transplantation are holding their own with top-selling drugs Prograf, and Vesicare. This past spring, the company introduced its flagship product, immunosuppressant Prograf, in the Indian market, and gained approval for additional indications of the drug in Japan for myasthenia gravis, a neuromuscular disorder, and ulcerative colitis. The company also gained FDA-approval for Vibativ for complicated skin and skin structure infections, which launched in November 2009. The drug was developed with partner Theravance, Inc. under a collaboration dating back to November 2005. The two companies will co-market the drug in the U.S. for the first three years following approval.

Other notable alliances during the course of the year include Astellas’ co-promotion agreement with Pfizer Japan for Caduet Combination Tablets and its joint venture with Maxygen aimed at creating “biosuperior” drugs. Pfizer Japan and Astellas will co-promote an oral combination drug of hypertension treatment Norvasc, sold by Pfizer, and hypercholesterolemia treatment Lipitor, co-promoted by Pfizer and Astellas. The Caduet Combination Tablets launched December 2009 in Japan and the term of the agreement extends through July 2016, which should help secure near-term future revenues.

The JV with Maxygen is focused on the development of Maxygen’s MAXY-4 program and other early stage programs for the treatment of autoimmune disorders. Astellas has an option to acquire all of Maxygen’s ownership interest in the JV within three years. Recently, the JV achieved a preclinical milestone.

The company’s pipeline certainly has grown to include a broader therapeutic base and the next few years will be telling. Should those early-stage cancer drugs progress, Asetllas’ oncology ambitions have the potential to prove fruitful. —KB

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