Takeda

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Company Headquarters

4 Chome Doshōmachi, Chuo Ward, Osaka, Japan

Driving Directions

Brand Description

We strive to transform lives. While the science we advance is constantly evolving, our core purpose is enduring. For more than two centuries, our values have guided us to do what’s right for patients and for society.

We know that changing lives requires us to do things differently. We start by listening to and addressing what really matters to patients, the people who love them, and those in the healthcare system who provide care. And that’s what inspires us all to be bold, push boundaries and set new standards that open up greater opportunities.

Key Personnel

NAME
JOB TITLE
  • Christophe Weber
    Representative Director - President & CEO
  • Akiko Amakawa
    Corporate Strategy Officer & CEO Chief of Staff
  • Andrew S. Plump
    Director - President, Research & Development
  • Asuka Miyabashira?
    President, Japan Pharma Business Unit?
  • Elaine Shannon
    Global Quality Officer
  • Gabriele Ricci
    Chief Data & Technology Officer
  • Giles Platford
    President, Plasma-Derived Therapies Business Unit
  • Julie Kim
    President, U.S. Business Unit, and U.S. Country Head
  • Lauren Duprey
    Chief Human Resources Officer
  • Marcello Agosti
    Global Business Development Officer
  • Milano Furuta
    Director
  • Mwana Lugogo
    Chief Ethics & Compliance Officer
  • Ramona Sequeira
    President, Global Portfolio Division
  • Takako Ohyabu
    Chief Global Corporate Affairs & Sustainability Officer
  • Teresa Bitetti
    President, Global Oncology Business Unit
  • Thomas Wozniewski
    Global Manufacturing & Supply Officer
  • Yoshihiro Nakagawa
    Global General Counsel

Yearly results

Sales: 28.2 Billion

Headcount: 50,000
Revenues: $28,165 (+6%)
Net Income: $953 (-55%)
R&D: $4,822 (+15%)

Takeda delivered strong growth in its fiscal year ended March 31, 2024. Revenue for the year was $28.2 billion, up 5.9% primarily attributable to favorable foreign exchange rates and growth across four of its five business units: Plasma Derived Therapies (PDT) Immunology, Gastroenterology, Rare Diseases, and Oncology. The increase in these business areas was partially offset by the decrease in Neuroscience. Revenue outside of these key business areas decreased mainly due to the decline in sales of Azilva (for hypertension) and the impact of generic entrants in Japan, as well as lower revenue contribution from COVID-19 vaccines in Japan.

The company’s largest revenue generator, gastroenterology, brought in $8 billion, up 11.1% for the year driven by Entyvio. Meanwhile, PDT came in second with $5.4 billion, up 20.7%. Aggregate sales of immunoglobulin products were $4.3 billion. Sales of each of Takeda’s three global immunoglobulin brands marked double digit percentage of revenue growth, due to continued strong demand globally and growing supply, as well as favorable foreign exchange rates. In Rare Diseases, revenue was $5.1 billion, up 6.5%. Notably, sales of Takhzyro increased 17.7% to $1.2 billion due to sustained launch momentum, expansion into new patient populations, rising diagnosis rates, the growth of the prophylactic market and favorable exchange rates. In Oncology, revenue was $3.1 billion, up 5.4%.

Meanwhile, in Neuroscience, revenue was $4.1 billion, down 1.7%. Sales of Vyvanse/Elvanse (for ADHD) were $2.8 billion, down -7.9% due to multiple generic entrants in the U.S. starting from August 2023, with the growth of the adult market in Europe and favorable foreign exchange rates partially offsetting the negative impacts.

In personnel news, in April 2024, Costa Saroukos stepped down as chief financial officer and was succeeded by Milano Furuta, president of Takeda’s Japan Pharma business unit. Furata will report to Christophe Weber, president and CEO, and will be based in Tokyo, Japan.

 

Acquired Assets

 

In January 2024, Takeda and Protagonist Therapeutics Inc. signed a worldwide license and collaboration agreement for the development and commercialization of rusfertide, an investigational injectable hepcidin mimetic peptide of the natural hormone hepcidin, currently in a pivotal Phase 3 trial for the treatment of Polycythemia Vera (PV). Under the terms of the agreement, Protagonist will receive an upfront payment of $300 million and is eligible to receive additional worldwide development and regulatory milestone payments, as well as commercial milestones and tiered royalties on ex-U.S. net sales. Takeda has rights for ex-U.S. development and is responsible for leading global commercialization activities.

In May, Takeda and AC Immune SA entered an exclusive, worldwide option and license agreement for AC Immune’s active immunotherapies targeting toxic forms of amyloid beta (Abeta), including ACI-24.060 for the treatment of Alzheimer’s disease. AC Immune will be responsible for completing the Phase 1b/2 trial and Takeda will conduct and fund all further clinical development and be responsible for all global regulatory activities as well as worldwide commercialization.

Most recently, in June, Takeda signed an option agreement with Ascentage Pharma to enter into an exclusive license agreement for olverembatinib, an oral, potentially best-in-class, third-generation BCR-ABL tyrosine kinase inhibitor (TKI), which is currently in development for chronic myeloid leukemia (CML) and other hematological cancers. If exercised, the option would allow Takeda to license global rights to develop and commercialize olverembatinib in all territories outside of mainland China, Hong Kong, Macau, Taiwan and Russia.

 

Alliances

 

Takeda and Biological E. Limited (BE), an India-based Vaccines and Pharmaceutical Company, entered a strategic partnership in February 2024 to accelerate access to QDENGA multi-dose vials (MDVs). These doses will ultimately be made available for procurement by governments in endemic countries by 2030 at the latest to support National Immunization Programs. BE will ramp up to a manufacturing capacity of up to 50 million doses a year, accelerating Takeda’s efforts to manufacture 100 million doses a year within the decade. The partnership will build upon existing manufacturing capacity for the vaccine at Takeda’s facility in Singen, Germany and Takeda’s long-term partnership with IDT Biologika GmbH.

In April, Takeda, Astellas Pharma Inc., and Sumitomo Mitsui Banking Corporation signed a master agreement to establish a joint venture company dedicated to the incubation of early drug discovery programs, primarily originating from Japan and toward the creation of innovative therapeutics. The joint venture aims to seamlessly cover the entire drug discovery process, spanning early drug discovery research through the inception of drug discovery startups. Takeda and Astellas will provide support to the joint venture company leveraging their expertise gained from global drug discovery research and development, aiming to accelerate open innovation in early-stage drug discovery, and toward the creation of start-up companies for the benefit of society.

In May, Degron Therapeutics, a company using its molecular glue-based targeted protein degradation drug-discovery platform to advance human health, entered a collaboration and exclusive license agreement with Takeda to discover and develop novel molecular glue degraders for multiple targets in oncology, neuroscience, and inflammation. The companies will collaborate to utilize Degron’s GlueXplorer platform to identify, validate, and optimize molecular glue degraders for specific therapeutic targets selected by Takeda. Upon reaching a certain stage of advancement, the projects would be transitioned to Takeda for further development and commercialization.

 

Sales: 30.3 Billion

Headcount: 47,347
Revenues: $30,368 (+13%)
Net Income: $2,390 (+38%)
R&D: $4,775 (+20%)

Maintaining its position at number 11, Takeda delivered strong growth in its fiscal year ended March 31, 2023, with reported revenue of $30.4 billion, up 13% and a 38% increase in earnings to $2.4 billion. Key pipeline milestones included the first approvals for dengue vaccine Qdenga, positive late-stage readouts for TAK-755 and fazirsiran, and the acquisition of Nimbus Therapeutics’ NDI-034858 for immune-mediated diseases.

Takeda reported strong double-digit growth across four of its five business units, gastrointestinal and inflammation, rare diseases, plasma-derived therapies, and neuroscience, largely driven by top sellers Entyvio, Immunoglobulin, Vyvanse, Takhzyro, and albumin products. The company’s largest revenue generator, gastroenterology, brought in $8.2 billion, up 25% for the fiscal year driven by Entyvio. Meanwhile, rare diseases came in second with $5.45 billion in revenue, up 18%. Revenue for Takhzyro, for hereditary angioedema, grew 47% driven by continued strong demand in the U.S. and geographic expansion. Notably, Plasma-Derived Therapies (PDTs) delivered outstanding growth with $5.1 billion in revenue, up 34%.

Neuroscience, with $4.8 billion in sales, grew 32% driven by increased demand for Vyvanse for ADHD in the adult market. Meanwhile, Oncology sales declined 6% to $3.3 billion impacted by the rapid generic erosion of Velcade sales in the U.S.

 

Acquired assets

 

For $4 billion upfront, and as much as $2 billion in commercial milestone payments, Takeda entered an agreement to acquire Nimbus Therapeutics’ NDI-034858, a potential best-in-class profile among new therapeutic class of selective allosteric TYK2 inhibitors for immune-mediated diseases, including psoriasis.

Also, under an exclusive license agreement with Innate Pharma, Takeda was granted exclusive worldwide rights to research and develop antibody drug conjugates (ADC) using a panel of selected Innate antibodies against an undisclosed target, with a primary focus in Celiac disease. For $5 million upfront, and as much as $410 million in potential development, regulatory and commercial milestones, plus royalties on potential sales, Takeda takes on future development, manufacture and commercialization of any potential products developed using the licensed antibodies.

Additionally, Takeda entered an exclusive licensing agreement with Hutchmed (China) Ltd. for the further development and commercialization of fruquintinib. For $400 million upfront, and as much as $730 million in additional potential payments, Takeda receives an exclusive worldwide license to develop and commercialize fruquintinib in all indications and territories outside of mainland China, Hong Kong and Macau.

Approved in China in 2018, fruquintinib is a highly selective and potent inhibitor of vascular endothelial growth factor receptors (VEGFR) -1, 2 and 3. Fruquintinib is orally administered and has the potential to be used across subtypes of refractory metastatic colorectal cancer (CRC), regardless of biomarker status. A Phase 3 trial of fruquintinib in refractory metastatic CRC, FRESCO-2, met its primary endpoint of improving overall survival and was generally well tolerated.

 

Facility expansions

 

Expanding its presence in Kendall Square, MA, Takeda signed a 15-year lease with BioMed Realty for approximately 600,000 sq.-ft. of research and development and office space to be built at 585 Third Street. The state-of-the-art facility allows Takeda to create a purpose-built R&D facility with labs of the future featuring modern design elements and upgraded technology to support the company in its efforts to advance innovation. The company will also expand its existing space in 650 East Kendall to include two additional floors.

Furthermore, in line with Takeda’s capital allocation policy of “Investing in Growth Drivers” the company is investing approximately $764.6 million to build a new manufacturing facility for plasma-derived therapies (PDTs) in Osaka, Japan. The investment enables Takeda to establish an end-to-end manufacturing facility for PDTs, which is expected to be operational by around 2030. The new site increases the capacity of Takeda’s current plasma manufacturing site in Narita, Japan almost five-fold.

 

Alliances

 

To aid in advancing its pipeline, Takeda is partnering with Adaptive Biotechnologies to leverage its clonoSEQ assay, and Arzeda to access its digital biology tool. The recent collaboration with Adaptive aims to measure Minimal Residual Disease (MRD) with clonoSEQ Assay to facilitate the development and commercialization of Takeda’s pipeline of treatments for lymphoid malignancies. MRD can be used to assess depth of response and to detect early signs of relapse prior to clinical symptoms. The clonoSEQ Assay is the first and only next-generation sequencing-based MRD test authorized by the U.S. FDA for MRD assessment in lymphoid malignancies and is highly accurate, sensitive, and standardized compared to other technologies used for disease burden assessment.

Additionally, an alliance with Arzeda will deploy AI-based protein design to optimize the properties of protein biologics. Takeda will leverage Arzeda’s Intelligent Protein Design Technology, which has the potential to accelerate the optimization of proteins that can be incorporated into therapeutic products. Applying the latest advances in digital biology, using computational design and machine learning algorithms, the collaboration aims to help improve therapeutic proteins in Takeda’s research pipeline.

Lastly, Takeda, Zedira and Dr. Falk Pharma GmbH entered a collaboration and licensing agreement to develop ZED1227/TAK-227, a Phase 2b investigational therapy for the treatment of celiac disease. TAK-227 is a potential first-in-class therapy designed to prevent the immune response to gluten in celiac disease, a serious autoimmune disease where the ingestion of gluten leads to inflammation and damage to the small intestine.

 

Pipeline highlights

 

Over the course of the year, Takeda gained several expanded indications for its therapies for pediatric use, including Takhzyro. The FDA approved the expanded use of TAKHZYRO to prevent attacks of Hereditary angioedema (HAE) in pediatric patients, making it the first prophylaxis treatment option for this age group.

Also, Qdenga, Takeda’s dengue vaccine, which has received several approvals to date, was recently approved by Brazil’s National Health Surveillance Agency (ANVISA) to protect against all four serotypes. Qdenga is the only dengue vaccine that is approved for use regardless of previous exposure and without need of pre-vaccination testing. Importantly, Takeda received Orphan Drug Designation from the Japanese Ministry of Health, Labour and Welfare for TAK-755 for the expected indication of thrombotic thrombocytopenic purpura (TTP).

TAK-755 is being developed globally for congenital and acquired TTP.

 

Sales: 29.3 Billion

Headcount: 50,000+
Revenues: $29,266 (+12%)
Net Income: $1,886 (-39%)
R&D: $4,314 (+15%)

TOP SELLING DRUGS

Drug Indication 2021 Sales (+/-%)
Entyvio ulcerative colitis, Crohn’s disease $5,061 22%
Immunoglobulin immunoglobulin deficiency $3,743 15%
Takhzyro hereditary angioedema $1,001 19%
Albumin PDT $873 56%
Alunbrig oncology $132 55%

Across Takeda’s five business units, the Japanese pharma major reported revenue of $29 billion, a 12% spike over the previous year. Gastroenterology is Takeda’s largest revenue generator with $8.49 in sales. The business grew 7% in 2021 driven by gut-selective Entyvio and anti-acid therapy Takecab.

Rare Diseases, with $5.93 in sales, is Takeda’s next largest revenue generator. While this business declined 1% due to competition in rare hematology, hereditary angioedema had growth of 4% driven by the strong performance of global market leader Takhzyro, which continued its geographic expansion with approval in Japan in March 2022. Post-transplant antiviral infection treatment Livtencity launched in the U.S. in December 2021 and has been well received by U.S. transplant centers.

The Plasma Derived Therapy Immunology business grew the most of all Takeda’s business segments. Revenues of $4.92 represented a 14% growth over the previous year. This was driven by continued strong growing global demand for the immunoglobulin portfolio and increasing demand for Flexbumin in China and the U.S., both enabled by improved supply, the company said. Takeda also reported 2021 plasma donation volume grew 16% compared to COVID-19-impacted 2020 and was up 3% over pre-pandemic levels.

Oncology, with $4.55 in revenue, grew 8% driven by increased market penetration and strong demand increases in growth and emerging markets, particularly China. Non-small cell lung cancer treatment Exkivity, which launched in the U.S. in September 2021, continued its global expansion with recent conditional approval in the UK. Lastly, Neuroscience sales of $4.68 marked a 10% growth driven by increased demand for Vyvanse following the impact of COVID-19 in 2020.

Pipeline highlights

Takeda currently has a pipeline of approximately 40 molecules in clinical development. In 2021, it received its highest total number of approvals—Japan (4 NMEs), China (3 NMEs), the U.S. (2 NMEs) and Europe (1 NME).

Vonvendi received approval from the U.S. FDA for adult patients living with severe type 3 von Willebrand Disease (VWD), making it the first and only treatment approved for routine prophylaxis to reduce the frequency of bleeding episodes in adults living with severe type 3 VWD receiving on-demand therapy.

Takhzyro was approved by Japan’s Ministry of Health, Labor and Welfare (MHLW) for adult and pediatric patients 12 years of age and older for prophylaxis against acute attacks of hereditary angioedema (HAE). The U.S. FDA approved a single-dose prefilled syringe injection for adult and pediatric patients 12 years and older. In addition, studies investigating Takhzyro for pediatric patients aged 2 to up to 12 years of age are ongoing and global regulatory filings for this patient population started in 2022.

Other candidates making their way through the clinic include, Alofisel, a treatment for Crohn’s disease, that showed clinical remission rate at six-months in the real-world Inspire study. Takeda also reported the first Phase 2 study of TAK-755 was completed. TAK-755 is the first and only ADAMTS-13 replacement therapy in clinical development to address congenital thrombotic thrombocytopenic purpura (cTTP) and immune mediated thrombotic thrombocytopenic purpura (iTTP), life-threatening thrombotic disorders caused by ADAMTS-13 deficiency. The company expects Phase 3 data for TAK-755 in cTTP in 2022 and potential filing for approval in 2022 as well.

Regulatory filings in Europe and endemic countries are ongoing for TAK-003, Takeda’s dengue vaccine candidate, and U.S. regulatory filings are planned for later this year. Additional clinical data (the DEN-301 4.5-year analysis) was presented at a scientific congress in June 2022.

In other development news, Takeda expanded its collaboration with JCR Pharmaceuticals to develop gene therapies that apply JCR’s J-Brain Cargo blood-brain barrier penetration technology for lysosomal storage disorders​. In another collaboration, Takeda partnered with Evozyne to develop proteins for gene therapies for genetic disorders within the inborn errors of metabolism and lysosomal storage disease areas of research.

COVID-19 efforts

Takeda has been active on many fronts in the fight against COVID-19. In fact, just recently, in April 2022, it received approval from Japan’s MHLW for Nuvaxovid Intramuscular Injection, the first recombinant protein-based COVID-19 vaccine approved for use in Japan, for primary and booster immunization in individuals 18 and older. Novavax licensed and transferred its manufacturing technologies to enable Takeda to develop and manufacture the vaccine at its facility in Hikari. At the time of press, Takeda was getting distribution efforts underway for Nuvaxovid doses purchased by the Japanese government.

In addition to its partnership with Novavax, Takeda also imported and distributed Moderna’s COVID-19 vaccine as part of a three-way partnership with Moderna and the MHLW.

Aside from vaccine development, Takeda has assessed its existing products for activity against the COVID-19 virus and co-founded the COVID R&D Alliance as a result. It also joined the Innovative Medicines Initiative (IMI) CARE consortium, the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) partnership and the COVID RED project.

Committed to cell therapy

One of the next frontiers for Takeda is accelerating next-generation cell therapies for cancer treatment. To support these efforts, Takeda broke ground in March 2021 on a new 38,000 square foot commercial cell therapy manufacturing facility at its Lexington, MA, campus. The new $84 million facility, which aims to be compliant with U.S., EU and Japan regulations, will be used for the production of oncology and other cell therapies.

The new ballroom-style facility will have a versatile, flexible footprint, allowing for future expansion to support the manufacturing of multiple commercial and clinical products, with additional capacity to expand the manufacturing space.

The new facility will utilize closed systems, isolator technology and robotics, and the technology will be an end-to-end single use system without the requirement of on-site sterilization. It will also use Takeda’s Enterprise Data Backbone (EDB) to consolidate data from multiple sources and virtual reality (VR) training for operators, so they can learn in a virtual environment before they enter the real facility. These features will enable the facility to ramp up quickly, and make manufacturing processes more robust, reproducible and scalable.

In addition to the new Lexington facility, Takeda opened a 24,000 square-foot cell therapy manufacturing facility in September 2020 at its R&D center in Boston. This facility provides end-to-end research and development capabilities and will produce cell therapies for clinical evaluation from discovery through Phase 2b trials.

In an effort to develop and deliver next-generation cell therapies faster, Takeda’s Cell Therapy Translational Engine (CTTE) provides product development, automation, engineering, chemistry, manufacturing and control (CMC), data management, analytical and translational capabilities in a single footprint to overcome many of the manufacturing challenges experienced in cell therapy development.

In other cell therapy news, in February 2021, Takeda unveiled plans to invest approximately $38 million at the Grange Castle site in Ireland to support the expansion of the company’s cell therapy production facility. The commercial scale cell therapy production facility is the first of its kind in Ireland.

In August 2021, Takeda broke ground on a new 15,000 square foot manufacturing facility, as well as a complete renovation of an existing 14,000 square foot manufacturing space in Thousand Oaks, CA. The $126 million investment increases the site’s capacity to manufacture additional products for the rare disease community.

In addition to infrastructure expansions, Takeda further strengthened its cell therapy capabilities in 2021 through acquisitions. In March, it acquired Maverick Therapeutics, a private biopharmaceutical company pioneering conditionally active bispecific T-cell targeted immunotherapies. Through the deal Takeda obtained Maverick’s T-cell engager Cobra platform and a broad development portfolio, including Maverick’s lead development candidate TAK-186 (MVC-101) for the treatment of EGFR-expressing solid tumors, and TAK-280 (MVC-280) for the treatment of patients with B7H3-expressing solid tumors.

In October 2021, Takeda acquired GammaDelta Therapeutics, a company focused on exploiting the unique properties of gamma delta T cells for immunotherapy. Through the acquisition, Takeda obtains GammaDelta’s allogeneic variable delta 1 gamma-delta T cell therapy platforms, which includes both blood-derived and tissue-derived platforms, in addition to early-stage cell therapy programs.

Sales: 28.9 Billion

Headcount: 47,495
Revenues: $28,911 (-3%)
Net Income: $3,401 (>100%)
R&D: $4,121 (-10%)

TOP SELLING DRUGS

Drug Indication 2020 Sales (+/-%)
Entyvio ulcerative colitis, Crohn’s disease $3,895 24%
Immunoglobulin immunoglobulin deficiency $3,039 12%
Vyvanse attention deficit disorder/hyperactivity $2,464 -1%
Advate haemophilia A $1,166 -19%
Velcade multiple myeloma $917 -15%
Lupron Depot hormone associated therapy $865 -13%
Ninlaro multiple myeloma $793 13%
Takhzyro hereditary angioedema $787 27%

Maintaining its position in the top 10 despite a 3% slip in revenues, Takeda’s top selling drugs Entyvio, a monoclonal antibody used in gastroenterology, and Photodynamic therapy Immunoglobulin used in immunology, along with strategic divestitures, supported underlying growth in 2020.

Takeda’s five key business areas of Gastroenterology, Rare Diseases, Plasma-Derived Therapies, Oncology and Neuroscience with $23.8 billion in revenue represent approximately 82% of the company’s total FY2020 revenues, and delivered 5% growth. Sales of Takeda’s 14 global brands were up 16% to $11.0 billion, and include top seller Entyvio, up 24%, Takhzyro, up 30% and Immunoglobulin, up 16%, which helped offset declines in neuroscience (-5%), and rare diseases (-7%), particularly Advate, which was down 19%. In Oncology, Velcade sales were down 15% and Leuprorelin sales were down 13%. Reported earnings growth of approximately 750% reflects gains on non-core asset sales and lower acquisition-related expenses (the Shire deal was finalized in January 2019).

According to the company, the overall impact of COVID-19 on financial results for the fiscal year ended March 31, 2021, was not material, with several offsetting factors, including benefits from prescribing trends during the pandemic, such as an expansion of certain products with a more convenient administration profile.

To date, Takeda’s non-core asset divestiture total reached ~$12.9 billion, exceeding its $10 billion goal, with 12 deals since January 2019. Most recently, Takeda sold a portfolio of approximately 130 select over the counter and prescription products, and two manufacturing sites to Orifarm for $670 million, a portfolio of four type 2 diabetes products to Teijin Pharma for JPY 133.0 billion, and sold Takeda Consumer Healthcare Company to Oscar A-Co KK, a company controlled by funds managed by The Blackstone Group Inc. and its affiliates, for JPY 227.7 billion.

Takeda also gained key approvals and advanced several assets this past year, and invested in rare disease and oncology assets, as well as cell therapy manufacturing capabilities.

Acquisitions and investments
In March 2021, Takeda entered an agreement to acquire Maverick Therapeutics to advance T-cell engager therapies for solid tumors and expand its novel immuno-oncology portfolio, for up to $525 million upfront and potential milestones. Takeda gains Maverick’s T-cell engager COBRA platform and a broad development portfolio, including lead development candidate TAK-186 currently in a Phase 1/2 study for the treatment of EGFR-expressing solid tumors, and TAK-280, which is anticipated to enter the clinic in the second half of Takeda’s FY2021 for the treatment of patients with B7H3-expressing solid tumors.

Takeda also secured global rights from Ovid Therapeutics to develop and commercialize Soticlestat for the treatment of Dravet Syndrome and Lennox-Gastaut Syndrome for up to $856 million in payments, including a $196 million upfront. The potential first-in-class therapy has been shown to reduce seizure frequency in children with Dravet Syndrome and Lennox-Gastaut Syndrome in a Phase 2 trial. Takeda Plans to Initiate Phase 3 studies in 2Q21.

Additionally, to help accelerate efforts to develop next-generation cell therapies, Takeda is expanding its cell therapy manufacturing capabilities with the opening of a new 24,000 sq.-ft. R&D cell therapy manufacturing facility at its headquarters in Boston, MA. The facility will provide end-to-end research and development capabilities and will initially focus on oncology with potential to expand into other therapeutic areas. Takeda currently has five collaborative oncology cell therapy programs expected to be in clinical development by the end of FY2021. The cGMP facility builds on cell therapy capabilities and increases capacity to supply cell therapies for global clinical trials.

R&D highlights
Takeda’s R&D model is focused on more targeted patient populations where there is potential for greater therapeutic benefit, smaller and less costly development programs, and faster tracks to registration with enhanced patent protection and marketing rights. The company plans to increase R&D investment to 522 billion JPY to advance 40+ prioritized NMEs and new partnerships, as well additional capabilities in oncology and data and digital sciences. In FY2020, Takeda gained 12 global and regional approvals in the U.S., EU, China and Japan.

The main driver for new product launches in the near term are 11 NMEs that include several potential best-in-class / first-in-class therapies, and two regional COVID-19 vaccines. Takeda anticipates five to six “Wave 1” new molecular entities (NMEs) to be submitted to FDA in FY2021, with the potential for four more approvals. The following highlights some of these therapies.

Recently, Takeda’s Dengue vaccine candidate TAK-003, was shown to prevent 83.6% of hospitalizations and 62% of Dengue illness overall, in an ongoing Phase 3 trial, with no identified safety risks through three years following vaccination. Regulatory filings are progressing in the EU and many Dengue-Endemic Countries; filing in in the U.S. is planned for later this year. According to the company, Dengue is the fastest-spreading mosquito-borne viral disease with an estimated 390 million cases and 500,000 hospitalizations each year globally, with limited prevention options.

Mobocertinib (TAK-788), a potential new oral standard of care for epidermal growth factor receptor (EGFR) Exon20 insertion mutation-positive metastatic non-small cell lung cancer (mNSCLC), has completed its NDA submission with a potential approval in FY2021. Mobocertinib was granted priority review by the FDA and is the first oral therapy specifically designed to selectively target EGFR Exon20 insertion mutations.

Meanwhile, primary analysis from a Phase 3 trial evaluating Maribavir (TAK-620) showed significantly more patients achieved cytomegalovirus (CMV) clearance versus conventional therapies in transplant recipients with CMV infection. The trial met key secondary endpoints, maintaining superior CMV clearance and is on track for NDA submission. The FDA granted the drug priority review and breakthrough therapy designation. If approved, Maribavir will be the first treatment indicated for post-transplant CMV infection in patients that are refractory, with or without resistance. Maribavir is Takeda’s fourth NME accepted for regulatory review within a six month period.
Also, Orexin (TAK-994), is a potential first therapy to treat orexin deficiency, which is associated with narcolepsy type 1, a rare, underdiagnosed and undertreated condition that disrupts the sleep awake cycles, and with narcolepsy type 2 and idiopathic hypersomnia to follow as potential additional indications.

These are in addition to Soticlestat acquired from Ovid Therapeutics and TAK-186 acquired from Maverick Therapeutics, as mentioned above.

COVID efforts
Takeda has partnered with the Government of Japan, Novavax and Moderna, to help accelerate the availability of COVID-19 vaccines leveraging its extensive global manufacturing and supply capabilities and building on its existing influenza pandemic preparedness efforts in Japan. Takeda also has a mutual agreement with IDT Biologika GmbH to use capacity at IDT for three months, previously reserved for Takeda’s dengue vaccine candidate, to manufacture Johnson & Johnson’s single-shot COVID-19 vaccine.

This past February the first subject was dosed in its Phase 1/2 immunogenicity and safety study of Novavax’ COVID-19 vaccine candidate (TAK-019) in Japan, and Takeda completed enrollment in its Phase 1/2 immunogenicity and safety study of Moderna’s COVID-19 vaccine candidate (TAK-919) in Japan. Results from the TAK-919 study are expected in 1H21 and results from the TAK-019 study in 2H21. Once available, results will be submitted to the Japan Pharmaceuticals and Medical Devices Agency (PMDA) as part of the NDA filing process. Pending regulatory approval, Takeda intends to start distributing TAK-919 in the 1H21 and aims to start distributing TAK-019 in late 2021.

Sales: 30.5 Billion

Headcount: 49,578
Revenues: $30,519 (+2%)
Net Income: $410 (n/a)
R&D: $4,566 (+56%)

TOP SELLING DRUGS

Drug Indication 2019 Sales (+/-%)
Entyvio ulcerative colitis, Crohn’s disease $3,194 32%
Vyvanse attention deficit disorder/hyperactivity $2,518 465%
Gammafard Liquid immunoglobulin deficiency $2,151 312%
Advate haemophilia A $1,453 402%
Velcade multiple myeloma $1,001 5%
Leuplin prostate cancer $798 1%
Ninlaro multiple myeloma $714 27%
Azliva hypertension $706 11%
Takecab acid-related diseases $669 27%
Trintellix depression $650 25%

Takeda was catapulted into this year’s Top 10 after its massive $62 billion acquisition of Shire in 2018. The deal was finalized in January 2019 and is one of the largest international acquisition deals in Japan’s history. The mega deal doubled Takeda’s pharma revenues, which grew to $30.5 billion in 2019 from $16 billion the year before. Backed by the Shire deal, Takeda now has firm footing as a top 10 R&D driven global biopharmaceutical company.

Broken down geographically, the U.S. led Takeda’s revenues, representing 48% of 2019 sales, followed by Europe and Canada (20%), Japan (18%) and growth and emerging markets (14%).
Takeda’s transformed global business platform is focused on 5 key business areas—Gastroenterology (21% of 2019 sales), Rare Diseases (20%), Plasma Derived Therapies (12%), Oncology (13%), and Neuroscience (13%), with growing brands and a strong R&D pipeline of promising therapies in these areas.

Takeda reported that its leading gastrointestinal (GI) therapy, Entyvio, its treatment for rare hereditary angioedema, Takhzyro, and plasma-derived therapies all delivered strong growth in 2019. Entyvio enjoyed a 33% sales spike while Takhzyro sales shot up 318%. Other notable contributors to 2019 revenue growth include the oncology drug Ninlaro, which grew 29%, neuroscience treatment Trintellix, up 25%, and the immunology drug Albumin/Flexbumin was up 20%.

During the year, Takeda divested its eye drug Xiidra to Novartis for $5.3 billion and its TachoSil Fibrin Sealant Patch to Ethicon for $400 million as part of its strategy to focus on core business areas following the Shire deal.

Takeda’s R&D engine is fueled by 14 global brands with more than 20 ongoing pivotal studies in new indications and geographies. The main drivers for new product launches are 12 unique New Molecular Entities (NMEs) in Wave 1, which Takeda says represent several potential best-in-class / first-in-class therapies targeted for launch by 2024 and have potential peak sales of more than $10 billion. In addition, Takeda has approximately 30 clinical-stage early development NMEs and next generation platforms under development.

Takeda has major expansion plans in China with more than 15 planned approvals over the next five years. In fact, during the fourth quarter Takeda received approval for Entyvio in China for the treatment of patients with moderate to severe active ulcerative colitis and Crohn’s disease.

Bolstering its R&D capabilities in 2019, Takeda opened a new research facility in San Diego, CA. The 165,000-square-foot facility is home to more than 250 employees focused on leveraging specialized drug discovery technologies and advancing discovery research in gastroenterology and neuroscience.

The facility is home to four research platform groups—structural biology, early target discovery, computational biology and biologics—that provide key capabilities to discover and advance promising molecules. The new research center in San Diego complements Takeda’s global Research & Development center in Cambridge, MA and its other global research site in Shonan, Japan.

Takeda’s R&D efforts are in four therapeutic areas—oncology, gastroenterology (GI), neuroscience and rare diseases—with targeted investments also committed to plasma-derived therapies (PDT) and vaccines. More than 50 percent of Takeda’s research pipeline focuses on non-small molecules, including biologics, peptides, oligonucleotides, cell and gene therapy, the microbiome and other modalities.

Immuno-oncology takes center stage
At the beginning of 2019, Takeda formed new research collaborations in immuno-oncology, an area of key strategic focus for the company. Through these collaborations, Takeda seeks to accelerate the discovery of next-generation cancer immunotherapies, including novel cell therapy approaches that may provide important opportunities for addressing the needs of patients with hard-to-treat cancers.

Takeda is collaborating with Memorial Sloan Kettering Cancer Center to discover and develop novel chimeric antigen receptor T-cell (CAR-T) products for the treatment of multiple myeloma, acute myeloid leukemia and additional solid tumor indications.

It exercised an option under its existing research collaboration with Noile-Immune Biotech, which originated in September 2017. Due to the success of the collaboration, Takeda exclusively licensed NIB-102 and NIB-103 for the treatment of various solid tumor indications, and will co-develop these CAR-T cell therapies with Noile utilizing the company’s proprietary “Prime” (proliferation inducing and migration enhancing) CAR-T platform.

Takeda’s exercised option for an exclusive oncology-targeted Humabody license from Crescendo Biologics will allow it to additionally evaluate these Humabody VHs for the development of novel CAR-T therapeutics. The development will leverage the unique properties of single-domain tumor-targeted binders as an alternative to conventional single-chain variable fragment (scFv)-based approaches.

Takeda’s diversification into next-generation cell therapy builds directly on its three strategic pillars in oncology: hematologic malignancies, lung cancer and immuno-oncology. Through collaboration with external partners and its newly established translational cell therapy engine, Takeda plans to deliver a rich pipeline of early-stage assets in the coming years.

R&D partnerships
During the year Takeda entered 38 new R&D collaborations with biotech and academia. With Evotec SE it entered a strategic, multi-year drug discovery collaboration to establish at least five drug discovery programs with the goal of Evotec delivering clinical candidates for Takeda to pursue into clinical development.

Sosei Group Corporation and Takeda entered into a multi-target partnership to discover, develop and commercialize novel molecules, including small molecules and biologics, that modulate G protein-coupled receptor (GPCR) targets. The partnerships could be worth more than $1.2 billion.

In another collaboration, Takeda and Skyhawk Therapeutics will use Skyhawk’s SkySTAR technology platform to discover and develop small molecule treatments for certain neurological disease targets.

StrideBio and Takeda partnered to develop in vivo AAV-based therapies for Friedreich’s Ataxia (FA) and two additional undisclosed targets that could be worth up to $700 million. These programs aim to utilize novel AAV capsids developed by StrideBio to improve potency, evade neutralizing antibodies and enhance specific tropism to tissues including the central nervous system.
LegoChem Biosciences entered a research collaboration and license agreement with Takeda for the development of antibody-drug conjugates (ADCs) in immuno-oncology that could be worth up to roughly $410 million.

HemoShear Therapeutics extended its partnership with Takeda to discover and develop additional novel therapeutics for liver diseases, including nonalcoholic steatohepatitis (NASH) in a deal worth $470 million if milestones are met.

Takeda Dunboyne Biologics entered into a collaboration with Applied Process Company (APC) in Dublin, Ireland to design, optimize and deliver scale-independent process improvements for Takeda’s portfolio of biologics-based medicines for rare diseases. The companies completed their first partnership program in June, which used advanced computational, fluid-dynamic models to better understand and characterize the process equipment at Takeda’s biologics facility in Dunboyne, Co. Meath. Takeda took official ownership of the new facility in June. This ‘paperless’ facility is designed with single-use technology to manufacture antibody and enzyme-based therapies for rare diseases.

Lastly, Takeda unveiled plans to open a new plant in Singen, Germany that will manufacture the company’s dengue vaccine candidate, TAK-003. Phase III results show the vaccine is effective against the mosquito-borne virus. The company began construction in 2016 and invested approximately $140 million to build the facility.

Sales: 16 Billion

Headcount: 27,230
Revenues: $15,967 (+2%)
Net Income: $1,684 (+62%)
R&D: $2,935 (+4%)

TOP SELLING DRUGS  

Drug Indication 2018 Sales (+/-%)
Entyvio ulcerative colitis, Crohn’s disease $2,428 34%
Velcade multiple myeloma $953 -7%
Leuprorelin prostate cancer, breast cancer, endometriosis $790 -1%
Azliva hypertension $639 11%
Dexilant acid reflux $624 5%
Ninlaro multiple myeloma $561 34%

The largest, and only mega-deal of 2018 was Takeda’s $62 billion acquisition of Dublin, Ireland-based Shire. The deal, announced in May and finalized in January 2019, propels Takeda into the top 10 pharma companies and is one of the largest overseas acquisition deals ever in Japanese history. Projected sales for 2019 are in the $30 billion range.

With the Japanese pharma market lagging, Takeda’s purchase gives it an expanded geographic footprint, scale, and most importantly, a bigger foothold in the U.S. To offset pricing pressures in the U.S., the deal bolsters Takeda’s portfolio of rare disease therapeutics, currently viewed as an under-saturated market of high value due to regulatory incentives and high drug prices.

In addition to creating leading positions in rare diseases and plasma-derived therapies, complementing strengths in oncology and vaccines, the deal bolsters its portfolios in gastroenterology and neuroscience as well.

While the Shire deal was being worked out, in September Takeda unveiled plans to move its U.S. headquarters and 1,000 employees from the suburbs of Chicago to the Boston area, where most of Shire’s operations existed—3,000 of its employees in Lexington and Cambridge. The Japanese pharma giant is now the largest biopharma firm in the Boston area, which has overtaken rival California as the number one biotech hub in the world.

Takeda continued to diversify its cancer research activities with collaborations in immuno-oncology, an area of key strategic focus for the company. An alliance with Memorial Sloan Kettering aims to discover and develop novel CAR-T products for multiple myeloma, acute myeloid leukemia and solid tumor indications.

It also exercised an option under a research collaboration with Noile-Immune Biotech, licensing NIB-102 and NIB-103 for the treatment of various solid tumor indications, and will co-develop these CAR-T cell therapies with Noile using their “Prime” CAR-T platform. The company plans to gain regulatory approval for human testing of NIB-102 by the end of this year.

Through collaboration with external partners and the newly established translational cell therapy engine, Takeda is laying the foundation to deliver a rich pipeline of early-stage assets in the coming years.

Sales: 14.4 Billion

Headcount:  22,000
Revenues:  $14,449  (+33%)
Net Income:  $4,272  (n/a)
R&D:  $1,763  (+23%)

Top Selling Drugs  

Drug Indication 2017 Sales (+/-%)
Hemophilia hematology $2,957 65%
Immunoglobulin Therapies immunology $2,237 96%
Vyvanse ADHD $2,161 7%
Cinryze hereditary angioedema $699 3%
Elaprase Hunter syndrome $616 5%
Lialda ulcerative colitis $570 -28%

Shire made major headlines this year surrounding the anticipated sale of the company. After rejecting numerous bids and offers, Japanese rival Takeda, finally came to an agreement to buy Shire for a whopping $62 billion. It represents one of the biggest pharma deals in history, and the largest-ever international takeover by any Japanese company. The deal is expected to close in the first half of 2019, and it wasn’t Shire’s only major sale of the year. In addition, Shire also announced the sale of its Oncology business to Servier S.A.S. for $2.4 billion. Shire’s Oncology business, which brought in $292 million in revenue in 2017, includes in-market products Oncaspar, Onivyde, and Calaspargase Pegol (Cal-PEG), which is under FDA review for the treatment of acute lymphoblastic leukemia, as well as an early stage immuno-oncology pipeline. Shire says that while the business has delivered high growth and profitability, the company concluded that it is not core to Shire’s longer-term strategy.

This year also brought numerous approvals for Shire. In June 2017, The FDA approved Mydayistm, a once-daily treatment comprised of three different types of drug-releasing beads for patients 13 years and older with ADHD. The FDA also approved a label expansion for Cinryze, making it available to help prevent angioedema attacks in children aged 6 years and older with hereditary angioedema. The condition results in recurring swelling in various parts of the body, including the abdomen, face, feet, hands and throat that can be can debilitating and painful.

Collaborations during the year were plentiful for Shire as well, especially within the area of Hemophilia. Notably, Novimmune S.A. entered into an agreement granting Shire exclusive worldwide rights to develop and commercialize an innovative, bi-specific antibody in preclinical development for the treatment of hemophilia A and hemophilia A patients with inhibitors.

Shire also entered into a collaboration with MicroHealth to support a free and secure care monitoring tool for hemophilia A and B patients with inhibitors. MicroHealth developed the app to help improve hemophilia patient care and outcomes through the ability to set reminders, track, store and selectively share personal health data with care team members. Shire’s role in the partnership is to help the start-up customize the tool with new features and information specifically for the 5-7 percent of hemophilia patients with inhibitors.

Sales: 11.4 Billion

Headcount: 23,906
Revenues: $11,397 (+78%)
Net Income: $327 (-75%)
R&D: $1,440 (-8%)

Top Selling Drugs 

Drug Indication 2016 Sales (+/-%)
Vyvanse ADHD $2,014 17%
Hemophilia hematology $1,789 n/a
Immunoglobulin Therapies immunology $1,144 n/a
Lialda ulcerative colitis $792 16%
Cinryze hereditary angioedema $680 10%
Elaprase Hunter syndrome $589 7%

At the beginning of 2016, Irish drug maker Shire catapulted itself into the top 25 companies after it bought American pharma firm Baxalta. The $32 billion mega-deal creates a global biotech projected to generate over $20 billion in annual revenues by 2020.

The combination of the two pharmaceutical giants creates a world leader in rare diseases, a platform for which Shire will now have leading products in each of the following growing, multi-billion-dollar therapeutic areas: hematology; immunology; neuroscience; lysosomal storage diseases; gastrointestinal/endocrine; and hereditary angioedema (HAE).

The combined company will also have a growing franchise in oncology, with approved products and innovative compounds in development, as well as a robust late-stage ophthalmics pipeline.

Altogether, there will be more than 60 programs in development, including over 50 that will address rare diseases, and the newly-approved Baxalta products Adynovate, Vonvendi and Obizur. Shire anticipates more than 30 recent and planned product launches from the combined pipeline, contributing approximately $5 billion in annual revenues by 2020.

On the heels of the deal, towards the end of the year, Shire unveiled plans to expand its operations in Cambridge, MA, establishing a rare disease innovation hub and increasing its footprint in Kendall Square, leasing a 343,000-sq.-ft. building with occupancy anticipated for the first quarter of 2019.

Shire will create a cross-disciplinary campus with teams spanning research, clinical development, medical affairs, business development, and other related functions. It will retain its current office, lab, and manufacturing space in Mass., including its presence in Lexington, where it’s been located since 2007. Shire currently employs more than 3,000 people in the state and as part of its growth in Kendall Square, Shire is undertaking a strategic review to identify which specific functions will be located there over time and plans to add nearly 400 positions.

At the tail end of the year, Shire U.S. Manufacturing entered into a multi-year supply agreement for an undisclosed product with AMRI. The product has been in AMRI’s portfolio through the required stages of development. This is the second such multi-year agreement between AMRI and Shire, as AMRI has also been supplying a neuroscience product to Shire.

Sales: 16.1 Billion

Headcount: 31,328
Revenues: $16,068 (+2%)
Net Income: $742 (-$1,196 FY14)
R&D: $3,075 (-10%)

Top Selling Drugs

Drug Indication 2015 Sales (+/-%)
Velcade multiple myeloma $1,440 9%
Leuprorelin prostate cancer, breast cancer, endometriosis $1,106 0%
Pantoprazole peptic ulcer $896 -3%
Lansoprazole peptic ulcer $796 -13%
Entyvio ulcerative colitis, Crohn’s disease $766 58%
Candesartan hypertension $754 -41%
Dexilant acid reflux $668 13%
Azilva hypertension $525 14%
Nesina diabetes $435 5%
Colcrys gout $413 -12%

The product liability lawsuits that were pending against Takeda in the U.S., which accused the company of failing to warn users about research that linked the diabetes drug Actos to an increased risk of bladder cancer, was settled for $2.7 billion in April 2015, hopefully resolving the matter for Japan’s largest pharma firm. Despite the difficulties created by the Actos suits, the fiscal year under review had many highlights. In gastroenterology, Takeda was granted marketing authorization for Entyvio (vedolizumab) in the U.S. and Europe. Entyvio is a biologic therapy planned and developed for moderate to severe active ulcerative colitis concomitantly with Crohn’s disease.

In oncology Takeda received approval from the FDA for an additional indication of  Velcade (bortezomib) for the retreatment of adult patients with multiple myeloma who had previously responded to Velcade therapy and relapsed at least six months following completion of prior Velcade treatment. The company also received approval from the FDA for an additional indication of Velcade for use in previously untreated patients with mantle cell lymphoma. As a promising successor proteasome inhibitor to Velcade, MLN9708 (ixazomib) is now in five Phase III clinical trials for patients with multiple myeloma and relapsed or refractory primary (AL) amyloidosis in Japan, the U.S., and Europe. Takeda was granted Breakthrough Therapy status from the FDA for MLN9708 for the treatment of relapsed or refractory systemic light-chain (AL) amyloidosis.

At the end of 2014 Takeda formed a dedicated global oncology business—Takeda Oncology—headquartered in Cambridge, MA. Comprised of Takeda’s global oncology commercial operations, the oncology business unit remains aligned with Takeda’s global oncology R&D function, the oncology therapeutic area unit, and Takeda’s oncology drug discovery unit. The company is currently investigating compounds across more than 17 forms of cancer, including ixazomib in AL amyloidosis and multiple myeloma as well as alisertib in relapsed/refractory peripheral T-cell lymphoma, recurrent ovarian cancer, and small cell lung cancer, among other malignancies.

On the R&D front, Takeda continued to intensify its focus on external innovation. One important example is the 10-year collaboration agreement between Takeda and the Center for iPS Cell Research and Application (CiRA) of Kyoto University into which it entered in April 2015. The agreement is to develop clinical applications of induced pluripotent stem (iPS) cells across multiple therapeutic areas.

With Mersana Therapeutics, Takeda expanded the ongoing collaboration to create Fleximer antibody-drug conjugate (ADC) drug candidates to include additional oncology targets. During the year Takeda also licensed exclusive rights to use ImmunoGen’s ADC technology to develop and commercialize targeted anticancer therapeutics for as many as two undisclosed targets with the option to take a license for a third target as well.

In another partnership, Takeda and Teva have established a new business venture to meet a range needs for generics in Japan, which is among the fastest growing generics markets in the world.

Sales: 16.4 Billion

Headcount: 31,328
Revenues: $16,424 (flat)
Net Income: $1,064 (flat)
R&D: $3,316 (-1%)

Top Selling Drugs 

Drug  Indication 2014 Sales  (+/-%)
Velcade multiple myeloma $1,276 21%
Candesartan hypertension $1,051 -31%
Leuprorelin cancer $1,036 -3%
Pantoprazole peptic ulcer $867 0%
Lansoprazole peptic ulcer $860 -17%

Takeda faced some difficulties in 2014, when a federal jury in Lafayette, LA reached a verdict in a lawsuit accusing Takeda of failing to warn users about research that linked the diabetes drug Actos to an increased risk of bladder cancer. Takeda was ordered to pay $6 billion in punitive damages and its partner Eli Lilly & Co. was ordered to pay $3 billion. Takeda and Lilly are contesting the verdict hoping that the fines will be reduced. Takeda developed and manufactured Actos and Lilly marketed the drug in the U.S. and Canada.

However, during the year, Takeda took steps to improve its situation and implemented strategies to boost R&D productivity. In the cardiovascular and metabolic area, Takeda filed a New Drug Application (NDA) in Japan for the once-weekly type 2 diabetes treatment SYR-472 (trelagliptin). In oncology, it obtained NDA approval in Japan for Adcetris (brentuximab vedotin) for the treatment of malignant lymphoma. In the central nervous system area, marketing authorization was granted by the European Commission for atypical antipsychotic Latuda (lurasidone) for the treatment of schizophrenia. In vaccines, Takeda obtained NDA approval in Japan for cell-cultured influenza vaccine H5N1 “TAKEDA” 1mL and cell-cultured influenza vaccine (prototype*4) “TAKEDA” 1mL for the prevention of pandemic influenza to be manufactured in the company’s Hikari Plant.

Some notable events during the year included an R&D alliance between GE Healthcare and Takeda to develop drugs as well as new diagnostic technologies targeting liver disease. Mersana Therapeutics and Takeda expanded their ongoing collaboration to create Fleximer antibody-drug conjugate (ADC) drug candidates to include additional oncology targets.

Also, Takeda opened its new office in Biopolis, Singapore. The expanded space will consolidate Singapore operations and serve as the Emerging Markets Business Unit headquarters, Takeda’s Development Center Asia, and the company’s Vaccine Business Unit.

 

KING’S REPORTThe Japanese giant is still trying to steady its ship after a difficult time over the past few years, and with the new foreign CEO Christophe Weber in situ, it’s a whole new ball game. Pursuing oncology still seems to be its aim, but having acquired Millennium’s Alisertib it’s struggling to make things move as quickly as it would like as the Phase III lymphoma trials for the drug have failed to come through with positive results. They are now relying on ixazomib to follow in the footsteps of  Velcade, which it hopes to submit to the FDA later this year for multiple myeloma.

—Adele Graham-King

 

 

Sales: 16.1 Billion

Headcount: 31,225
Pharma Revenues: $16,453 (9%)
Net Income: $1,066 (-27%)
R&D Budget: $3,358 (6%)

Top Selling Drugs

Drug  Indication  2013 Sales (+/- %)
Candesartan hypertension $1,507 -14%
Leuprorelin prostatic cancer $1,206 8%
Pioglitazone ype 2 diabetes $1,196 37%
Lansoproazole peptic ulcers $1,148 8%
Pantoprazole GERD $1,050 25%
Velcade multiple myeloma $924 73%
Colcrys gout $506 18%
Dexilant GERD $486 4%
Nesina type 2 diabetes $389 5%
Uloric high uric acid $263 92%
Amitzia IBS $253 3%
Calcium hypertension $185 15%
Adcetris Hodgkin lymphoma $136 5%

In late June, Takeda Pharmaceuticals held its 13th ordinary general meeting of shareholders, and there was a bit of tension there.  The company appointed Christophe Weber, a veteran of GSK who is French, as the company’s president and COO, with Yasuchika Hasegawa remaining Chairman and CEO.

As news magazines reported,this was the first time a foreigner had been appointed as a senior executive at the venerable Japanese company.   Although the company’s shareholders reportedly voted for Mr. Weber by a large margin, one group of shareholders questioned his appointment and Takeda’s globalization strategy, which has included acquisitions of drugmakers like Nycomed of Switzerland and Millennium Pharmaceuticals of the United States.

In addition, media reported that over 100 members of the Takeda family and former executives signed a letter of protest, reportedly based on fear that he might approve Takeda’s sale to a foreign company.

Chairman reaffirms the need for growth and diversity
The company’s chairman Hasegawa addressed criticism of the Millenium and Nycomed acquisitions at the meeting, before the live Q&A.

“Takeda’s presently decreasing profit is not the effect of these acquisitions, but rather due to structural changes that have progressed rapidly, particularly in Japan and the U.S., such as decreasing sales due to generic drug penetration.  Following the patent expiry of Takeda’s four blockbusters that had previously driven our performance, as well as decreasing profitability due to the decreasing ratio of inhouse products.

Post-Blockbuster Era Challenges
I’d like to illustrate this through the example of Actos, one of the largest factors in our decreasing profits. Global sales of Actos decreased from 387.9 billion yen in fiscal year 2010 to 36.6 billion yen in 2013 following expiration of its patent protection.The acquisitions were countermeasures designed to assure and recover our growth.  With Millennium, Takeda gained access to a strong oncology franchise and strengthened our presence in the U.S., the largest market in the world.

With the Nycomed acquisition, Takeda gained attractive positioning in locations where we were not previously, thus expanding our global footprint to areas from which we can now launch products that we developed ourselves.

Millennium is an important subsidiary in charge of R&D in oncology. Sales in the U.S. for the multiple myeloma drug Velcade were 95 billion yen in 2013, 30% up from the previous year, and we recovered almost 35 billion yen in royalties. Entyvio was approved in the U.S. and Europe and has been launched and has the potential to generate blockbuster sales. MLN9708 is in the final stages of development as Velcade’s successor in our multiple mueloma franchise, and is now in Phase III development…”
Takeda’s leadership seems committed to looking within and without its boundaries to strengthen its innovation.

Sales: 17 Billion

Headcount: 30,481
Pharma Revenues: $16,961 (-2%)
Total Revenues: $18,843 (-2%)
Net Income: $1,588 (1%)
R&D Budget: ($3,92410%)

Top Selling Drugs

Drug Indication $ (+/- %)
Actos diabetes $1,487 -60%
Blopress hypertension $2,052 -25%
Prevacid GERD $1,333 -14%
Lupron prostate cancer $1,410 -8%
Protonix GERD $944 92%
Velcade multiple myeloma $882 20%
Enbrel rheumatoid arthritis $523 -1%

Account for 51% of total pharma sales, down from 66% in 2011

A 5% drop in the value of the yen kept Takeda from taking advantage of Bristol-Myers Squibb’s weakness. In constant currency, Japan’s largest pharma posted a 3% gain in drug revenues in fiscal 2012 (which ended March 31, 2013).

Somehow, Takeda managed to post that 3% increase in pharma sales, even though its key products dropped 21% (!) from their 2011 figures, led by a $2.3 billion drop in Actos revenues. The company doesn’t break out sales of individual products very clearly, so we may be missing something in the reading, but even adding in the sub-$500 million products that Takeda lists in its annual statement and databook, sales of “major products” fell 10%, or $1.2 billion, in 2012. Accounting for both that and its reported growth means that there’s $1.8 billion of “other” floating around in Takeda’s pharma books. Sure wish we had loose change like that in our sofa cushions.

Opaque accounting notwithstanding, Takeda is trying to stick to a growth path despite losses from Actos and Blopress from generic competition. The acquisition of Nycomed has helped with that, providing nearly $1.0 billion in Protonix revenues (and a sizeable infringement settlement; see Pfizer’s report for more on that) and entre into emerging markets where Takeda had little penetration, particularly Russia, Brazil and China.

In the U.S., it hopes for a big diabetes score with its DPP4 inhibitor, Nesina, which was approved by the FDA in January along with two combo-drugs (with Actos and metformin, respectively). Takeda also expects solid performance in the U.S. from the gout drugs that came over with last year’s URL Pharma purchase, Uloric and Colcrys.

In May 2013, Takeda unveiled the latest in its rolling three-year mid-range plans. The mid-range strategy includes focusing on six therapeutic areas — Cardiovascular & Metabolic, Oncology, CNS, Immunology & Respiratory, General Medicine, and Vaccine — and getting more efficient at marketing, sales and manufacturing, using Nycomed’s legacy infrastructure to improve procurement methods.

The biggest organizational news tied to that plan was the decision to integrate the Millennium Oncology unit into Takeda more fully. In May 2013, Takeda announced that Millennium’s chief executive officer, Deborah Dunsire, would step down, to be replaced by her lieutenant, Anna Protopapas. In a Pharmalot interview, Ms. Protopapas commented, “The driver here is to really capture synergies and capturing the way we do . . . back-offce operations, the ways of doing development and leveraging efficiencies.” Oncology will still be led by Millennium’s Cambridge, MA campus, but various functions will be streamlined for efficiency and savings. She noted that a third of Takeda’s R&D budget is spent on oncology.

Along with its new three-year plan, Takeda unveiled its “Vision 2020” strategy for the future. It was a bit short on details, but had plenty of corporate cheering and stressed the need for diversity in its talent pool. The company made several smaller buys in the past year, mainly to shore up its new vaccine division, but it’s anybody’s guess as to whether Takeda will climb up our ranks as it gets past the Actos and Blopress patent cliffs.


Acquisition News
Target: Inviragen
Price: $35 million
Announced: May 2013
What they said: “Takeda has taken another major step toward its goal of establishing a world-class global vaccine business by acquiring Inviragen and its advanced vaccine candidate against dengue.”

—Rajeev Venkayya, M.D., executive vice president, head of Takeda’s Vaccine Business Division

Target: Envoy Therapeutics
Price: $140 million, including upfront and contingent payments
Announced: November 2012
What they said: “Since our initial investment in 2009, it has been clear to us that Envoy’s scientific excellence in combination with their vision for the utilization of bacTRAP technology have great potential to create and explore truly innovative targets across multiple therapeutic areas.”

—Dr. Paul Chapman, general manager of Pharmaceutical Research Division at Takeda.

Target: LigoCyte Pharmaceuticals
Price: $60 million upfront, plus milestones
Announced: October 2012
What they said: “This acquisition is a major step forward in the expansion of Takeda’s vaccine business, and a demonstration of Takeda’s dedication to preventing illness in children and adults around the world.”

—Dr. Rajeev Venkayya


Lowe Down
Takeda’s move this year to take direct control of Millennium, after a period of hands-off management, doesn’t look like the act of a company that’s confident about the future. Leaving that site alone was a great idea, they said, and completely the right plan — until it wasn’t. But Takeda has been scrambling ever since the expiration of the Actos patent — despite many efforts over the years, nothing ever came along that could make up for that revenue when it finally went away. There seems to be a lot in the late-stage pipeline, but that does not equal revenue, not quite.

Takeda’s chief executive officer has been talking about cozying up to academia for new ideas; it’s a popular strategy, but not one that has much to point at so far. And the company is also talking about “urgency,” which is one of those words I’ve never been sure about. In the abstract, I can see the point, but in practice, I worry that it just stirs people up to look busy. To get all Zen about it, urgency has to come from within — it doesn’t get applied externally, not if you want it to have any long-term efficacy.

—Derek Lowe

Sales: 17.3 Billion

 

Headcount: 30,305
Pharma Revenues: $17,257  (16%)
Total Revenues:$19,163 (15%)
Net Income: $1,577 (-46%)
R&D Budget: $3,580 (6%)

Top-Selling Drugs

Drug Indication $ (+/- %)
Actos diabetes $3,762 -17%
Blopress hypertension $2,747 8%
Prevacid GERD $1,551 -1%
Lupron prostate cancer $1,533 13%
Velcade multiple myeloma $738 24%

Account for 60% of total pharma sales, down from 72% in 2009PROFILE

A strong Japanese yen pushed Takeda to the #11 spot in our ranks, otherwise its comparable currency growth would have left it behind Teva. A 9% increase in the yen’s value against the dollar also made Actos’ decline seem less horrible than it was: a 24% drop in sales, year against year. Even with the currency boost, Actos has shed more than $1.3 billion from its peak.
The acquisition of Nycomed, which closed at the end of September 2011, allowed Takeda to diversify its geographic base from 28 countries to 70, and spread out its portfolio to get away from a reliance on a few key (and aging) products. It’s questionable how useful a strong European infrastructure is going to be in the years ahead, so it’s good that Nycomed had operations in many emerging markets, too.
Takeda didn’t break out Nycomed’s half-year contribution to its revenues (Japanese fiscal years end on March 31), but it expects to see around $3.8 billion in annual sales from that unit. That will help offset the pending drop in Actos revenues when that drug goes generic in the U.S. in August 2012. (It remains to be seen how much it’ll cost to settle the thousands of U.S. liability lawsuits stemming from Actos, but Nycomed money should help on that front.)
In the short term, the company’s fortunes will be buffered by Nycomed and its smaller acquisitions. Longer term, Takeda would love to ease into the post-Actos era with U.S. approval for alogliptin, its new DPP-4 inhibitor for diabetes. Takeda received a complete response letter for alogliptin’s NDA and provided post-marketing information for the drug, which is approved as Nesina in Japan. The company didn’t reveal the contents of the letter, nor whether new trials would be required in addition to Takeda’s ongoing ones. The FDA hit alogliptin with a CRL its first time around, in 2009. Takeda’s also trying to gain approval for fixed-dose combos of alogliptin with Actos and with metformin.
Takeda is a company in transition. Shortly after the deal closed, Takeda got to work “maximizing synergies.” In January 2012, the company announced layoffs of 2,100 in Europe and another 700 in the U.S., intended to yield savings of $2.5 billion. In May 2012, the company revised its ongoing Mid-Range Plan to cover the 2012-2014 span. The plan is now to get back on a sustainable growth path after Actos with that diversified product line and new markets, while trying to improve R&D with something called the Proof of Concept & Competitiveness model, intended to “rigorously discern which pipeline drugs will be competitive in the market over the medium to long term,” according to a Takeda statement.
It looks like vaccines will be part of that pipeline. Takeda established a vaccines division in January 2012, with hopes of expanding beyond the Japanese market, where it’s been active
for 60 years. Dr. Rajeev Venkayya was named leader of the division, leaving his role as director of Vaccine Delivery in the Global Health Program at the Bill & Melinda Gates Foundation.
Throughout the year, the company made a series of internal moves, reassigning directors, consolidating departments, and otherwise engaging in a transformation of the way Takeda does business. In May 2012, Takeda closed its South San Francisco bio-research site and consolidated it with San Diego, creating the new Takeda California unit. The company got rid of its International Operations roles and replaced them with a chief commercial officer to preside over global sales, except for Japan and the Millennium business acquired in 2008. The General Manager Office was created in June 2012 to oversee other corporate departments.

Is it an overdue streamlining of Takeda’s structure, or merely deck chairs being rearranged aboard the Titanic?


The Lowe Down
I have to give Takeda some credit for changing the name of their U.S. subsidiary back to plain ol’ “Millennium”, after a couple of years of hanging “The Takeda Oncology Company” after it. Beside making me think of the Artist Formerly Known as Prince, that named just served to highlight the company’s (mostly futile) efforts to achieve name recognition in the U.S. The thing is, name recognition doesn’t buy you very much in pharma — in some cases, when people have come to actively dislike a company, it’s actually a negative. That’s not something that they teach you much about when you’re getting a marketing degree, I’ll bet.
So I hope this means that the company is giving up on that effort and concentrating on quietly making new drugs and making new money from them. As for the older ones, they’ve probably gone about as far as they can go in maximizing Velcade, which will probably hold the title of Most Lucrative Boronic Acid Drug for many years to come.
One cloud on the horizon is the continuing flow of lawsuits over Actos, the company’s PPAR drug from the diabetes market. Depending on how those go, they might make Takeda one of several companies that might wonder if they’d have been better off never hearing of the whole drug class — or of diabetes in general, since their efforts to combine Actos with a DPP-IV inhibitor are somewhat stalled.
But there are quite a few things in the clinic still. Takeda looks to be a reasonably stable place for the near term, and the near term is nothing to sneeze at in this business.

—Derek Lowe


ACQUISITION NEWS

Target: Intellikine
Price: $190 million upfront, plus $120 million in potential clinical milestones
Announced: December 2011
What they said: “Intellikine has advanced three programs against the PI3K/mTOR pathway into human clinical testing in just four years. We are pleased that Takeda recognizes the potential of our clinical-stage programs as well as our strong pipeline and discovery engine.”
—Troy Wilson, Ph.D., J.D., president and 
chief executive officer, Intellikine
Target: URL Pharma
Price: $800 million plus undisclosed milestones
Announced: April 2012
What they said: “This acquisition expands Takeda’s gout treatment portfolio and leverages our expertise in primary care.”
—Douglas Cole, president, 
Takeda Pharmaceuticals U.S.A. 
Target: Multilab
Price: $266 million
Announced: May 2012
What they said: “Takeda has ambitious plans for growth in emerging markets. Brazil is our second largest emerging market after Russia/CIS in terms of revenues and the acquisition of Multilab is a clear signal of our intention to become a significant player both in Brazil and other high-growth markets.”
—Jostein Davidsen corporate officer, head of 
emerging markets commercial operations, Takeda

Sales: 14.8 Billion

Headcount: 19,654
Pharma Revenues: $14,829 (4%/-4%*)
Total Revenues: $16,607 (5%/-3%*)
Net Income: $2,900 (-10%-17%*)
R&D Budget: $3,380 (6%/-3%*)

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

Top-Selling Drugs in 2010

Drug

Indication

$

(+/- %)

Actos

diabetes

$4,538

10%

Blopress

hypertension

$2,551

8%

Prevacid

GERD

$1,563

-33%

Lupron

prostate cancer

$1,362

5%

Velcade

multiple myeloma

$594

19%

Account for 72% of total pharma sales, down from 73% in 2009

PROFILE

A favorable shift in exchange rates makes Takeda look better than it is. In yen, Takeda fell 4% in pharma sales, walloped by the loss of patent protection for Prevacid in the U.S. Revenues dropped by a third to $1.5 billion for Prevacid, while that 9% currency boost provides an artificial $1.2 billion boost in Takeda’s revenues.

Prevacid’s precipice provides prelude to Takeda’s primary problem: Actos’ U.S. patent expiration. In December 2010, Takeda settled with a dozen generic companies to stave off their challenges to the diabetes franchise’s patent protection. Four of the generic firms will be licensed to hit the U.S. market in August 2012, while the others will be allowed in after the 180-day exclusivity period. ACTOplus met and duetact will see generic competition in December 2012. Actos sales in the Americas region amounted to $3.5 billion in 2010.

In June 2011, France and Germany banned use of Actos after a study showed an increased risk of bladder cancer for some users. Actos only posted $345 million in sales in Europe for Takeda, so the ban won’t be too damaging to Takeda’s prospects. The FDA has also asked that Takeda update Actos’ label to warn about that cancer risk in patients taking the drug for more than a year at its highest dose. So much for Actos benefiting from the withdrawal of competitor Avandia.

So with Prevacid down the tubes and Actos facing a 2012 cliff, what can Takeda do to stay relevant? Buy another pharma!

In May 2011, Takeda made a $9.1 billion acquisition of Nycomed, after rumors of courtship swirled. (The deal also includes assumption of net debt, bringing the total value to $13.7 billion.) The acquisition, provided it passes antitrust muster, will add around $4.0 billion to Takead’s revenues, excluding the U.S. dermatology franchise, which was excluded from the acquisition. Those sales will help diminish the impact of Actos’ post-2012 decline. (Nycomed was dealing with its own post-patent plunge for Protonix.)

A week before the acquisition, Takeda rolled out a 2011-2013 business plan to “transform the company into a new Takeda.” The new plan modifies the 2010-2012 policy known as “the Vision,” retaining the goal of making 2015 comparable to 2010’s financial levels, with room for growth. To that end, the company will move away from mature, large-scale products (by necessity), and try to develop a “diverse product lineup centered on new treatments.” The company also planned to accelerate its moves into “newly penetrated countries and emerging markets,” according to the new plan. The U.S. and Japan account for around 85% of Takeda’s revenues.

So how does the Nycomed acquisition fit into the strategy? Well, Nycomed has a diverse portfolio and a marketing infrastructure in Europe and some emerging regions, so it could help jump-start Takeda’s strategy. More than half of Nycomed’s growth comes from emerging regions. Takeda has been looking to boost is presence in Russia and the former Soviet states. Nycomed has more than 12,000 employees, four R&D centers in Europe and India, and 15 manufacturing sites. Takeda projects approximately $350 million in synergies (read: layoffs of overlapping functions) from the deal.

Also, Nycomed’s commercialization partner, Forest Labs, received approval in March for Daxas, a first-in-its-class maintenance treatment for Chronic obstructive pulmonary disease (COPD). The approval triggered a $182 million milestone payment to Nycomed. Takeda will receive royalties from Forest’s U.S. sales of Daxas. Daxas was approved in April 2010 in Europe and Takeda estimates its non-royalty portion of sales could reach $720 million by 2015.

Takeda’s not just going for inorganic growth. The company gained FDA approval in February 2011 for Edarbi, a once-daily antihypertensive that proved more effective at lowering blood pressure than Diovan and Benicar. Estimates of Edarbi’s sales potential varied pretty widely, topping out at $750 million by 2015.

Takeda’s last major acquisition, the $8.8 billion purchase of Millennium Pharmaceuticals in 2008, has yet to bear fruit, outside of the performance of cancer drug Velcade, which posted 19% sales growth to hit $594 million last year (10% growth in yen). We’ll see if the big revenue boost that Nycomed offers, along with its marketing structure and pipeline, are enough to keep Takeda relevant and fulfill the Vision for 2015.  —GYR


OUTSOURCING NEWS

In February 2011, Takeda entered into strategic partnerships with Covance and Quintiles. The CROs will help Takeda plan and execute global development programs to support new compounds in all therapeutic areas, except oncology, and will contribute clinical development capabilities and central laboratory services.

The move is part of the company’s global program-level sourcing strategy to increase operational efficiency. “Through these relationships, Takeda will move toward a fully virtual outsourcing model combining the expertise and capabilities of Takeda with those of Covance and Quintiles to improve productivity and facilitate Takeda’s global growth,” according to a company statement.

In October 2010, Takeda North America signed a strategic IT services outsourcing pact with Accenture. Accenture will provide Takeda with application and infrastructure outsourcing services, including development, testing, and maintenance of all applications supporting Takeda’s operations, and service desk management, data center management, server and storage management, end-user computing, and network management.


ACQUISITION NEWS

Target: Nycomed

Price: $13.7 billion

Announced: May 2011

What they said: “Nycomed enables Takeda to maximize the value of our portfolio and gives us an immediate strong presence in the high-growth emerging markets while doubling Takeda’s European sales.”

—Yasuchika Hasegawa, president and CEO of Takeda


THE LOWE DOWN

Takeda, the flagship of the Japanese pharma industry, has been sneaking up on people. Every year or so they make another acquisition (Millennium, Nycomed) and sign another batch of codevelopment deals. I’m still pretty sure that their name would never come up if you stopped people on the street and asked them to name a bunch of drug companies, but that doesn’t seem to bother them much. They just keep on expanding.

I notice, though, that when they bought Nycomed, the CEO said that he hoped the smaller company’s entrepreneurial culture could seep over into the rest of the company. Wasn’t that supposed to happen when they bought Millennium, too? You could also wonder about a company that’s looking to the Swiss to bring in some of wild, freewheeling style, but all things are relative.

Takeda does seem be experiencing the Curse of the PPARs with Actos, which isn’t very timely, since the company just lost Prevacid this year. But compared to some of the other patent problems around the business, Takeda’s look relatively benign. Things should be quiet for the next couple of years, and then we’ll see what happens when the new drugs kick in. —Derek Lowe

Previous Profile: Teva Pharma // Next Profile: Bayer Healthcare

Sales: 14.2 Billion

Headcount: 19,654
Pharma Revenues: $14,204 (+3%/-5%)
Total Revenues: $15,803 (+3%/-5%)
Net Income: $3,210 (+37%/+27%)
R&D Budget: $3,195 (-29%/-35%)

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

2009 Top Selling Drugs
Drug Indication Sales (+/-%)
Actos diabetes $4,147 +7%
Prevacid GERD $2,351 -13%
Blopress hypertension $2,393 +4%
Lupron prostate cancer $1,317 +4%

Account for 72% of total pharma sales, down from 73% in 2008.

 

PROFILE

Look out! It’s a new Takeda, too! In May 2010, the company unveiled its three-year transformation plan. The strategy comes on the heels of its 2006-2010 plan to become a world-class pharma company. Sure, you can nitpick about some aspects of how they got there, but the company stuck with its vision of going global, integrating TAP to build a U.S. network, and moving up the world ranks (partly as a result of bigger competitors getting snapped up).

So why the new plan? For one thing, all of its major drugs dropped in sales last year in reported currency (the appreciation of the yen makes the results look better than they were), with Prevacid revenues dropping $400 million in 2009. The U.S. patent expired for that drug in November 2009.

The Lowe Down

It wasn’t so long ago that Takeda would never have shown up on a list like this. But as the names thin out above them, here they are. They’ve been increasing their presence in the U.S. for years, in a remarkably benign way — their treatment of Millennium seems so far to be a model of restraint, tact, and respect. Even their layoffs were abnormal, since they hardly seem to have touched people in the labs. Most of the positions lost seem to have been back at headquarters, or in the sales force.

What can they be thinking? Haven’t they looked around them and realized that you’re supposed to quickly loot your acquisitions for the most likely near-term winners and then heave half the staff out the door in the general direction of Burger King? Pay attention, people — it’s not like the rest of the industry hasn’t been showing you how to do it, again and again.

The company seems to want to be a player in oncology, which is fine, as far as it goes. The problem is, everyone else seems to want to be one, too, and some of them made that decision quite a bit before Takeda did.
One last worry — a look around their press releases nets you a lot of talk about the company’s Vision, and the progress toward a New Takeda. So far, my own experience with Long-Term Visions in this business has been pretty poor. I hope their look into the future works out better. For now, I see a lot of Vision posters, desk accessories, and slogans in their future. Prove me wrong, please! —Derek Lowe

On top of that, Takeda’s diabetes efforts continued to stumble when the company received a Complete Response Letter from the FDA for its combo of DPP-4 inhibitor alogliptin and Actos. The letter wasn’t unexpected; Takeda received one in June 2009 for alogiptin’s NDA. And, in fact, THAT letter wasn’t unexpected; the FDA had already requested a new cardiovascular safety study for alogliptin in December 2008. Takeda began the 5,400-person safety trial in September 2009, with an expected end-date of December 2014. The company hopes to submit interim data after two years to fulfill the FDA’s new guidance criteria.

Alogliptin did get approval for type 2 diabetes in the Japanese market, where it’s sold as Nesina. In June 2010, Takeda launched Nesina in Japan along with two other drugs: Vectibix, a colorectal cancer drug in-licensed from Amgen, and Unisia, a fixed-dose combo of Blopress and amlodipine besilate, for hypertension. THe company gained approvals of those drugs in April 2010, along with Metact, a combo of Actos and Metformin, and Rozerem, an insomnia treatment that featured absolutely bizarre ads when it was marketed in the U.S. I can only imagine how the ad campaign’s going to look in Japan.

Shrink To Grow

Overall, the business environment of the world changed pretty radically during that 2006-2010 timeframe, necessitating a massive rethink of the company’s prospects. Earlier plans to reach sales of 2 trillion yen by 2015 have been scrapped. Now, the company is targeting net sales of 1.33 billion yen in 2012. Net sales were 1.46 billion yen in 2009, so it looks like Takeda is being honest with itself about its pending patent cliff.

Within pharma, the new strategy is to focus on three core therapeutic areas: Metabolic & CV, Oncology, and CNS Diseases. The company contends that its R&D model has shifted from “quantity and speed” to “quality”, according to its annual report.

In July 2009, the company began work on its new research facilities, which are intended to serve as the center of the its global research network. The site is expected to be finished at the end of fiscal 2010 (Takeda’s FY runs from April 1 to March 31).

The new plan encourages M&A activity, but Takeda didn’t make any acquisitions in the past 12 months. That’s not to say the company wasn’t expanding; Takeda established operations in a number of regions, adding subsidiaries in South Korea, Brazil, Mexico, Turkey, Sweden, Norway, Denmark, Belgium and Luxembourg during the past year. Earlier in 2009, Takeda added operations in Spain, Portugal, Ireland and Canada. Under the new plan, the goal is to cover 90% of the global market by FY2012. I’d expect to see some regional M&A activity in the next 12 months.

Howdy, Pard’ner!

Takeda spent plenty on development and co-marketing agreements this year, in an attempt at boosting its pipeline. In April 2010, the company paid $60 million upfront to Seattle Genetics to buy non-U.S./Canada rights to an ADC to battle lymphoma. The deal includes another $75 million in development costs and as much as $230 million in various milestones.

In November 2009, Takeda bought into Amylin’s anti-obesity pipeline, paying $75 million upfront with a potential of more than $1 billion in milestones, plus royalties, for co-development rights to two lead compounds, as well as other pipeline products. In February 2010, the companies moved one of the lead compounds (pramlintde/metreleptin combination) into Phase III; the other lead was inferior to it and development was stopped.

In December 2009, Takeda allied with Pfizer to co-promote Actos in China. The company had been selling Actos in China since 2004, but Pfizer’s sales network may give it a big boost in that growing market.

Four months later, Takeda bought into an Alzheimer’s treatment developed by Janssen, a J&J unit. The drug was submitted to Japan’s Ministry of Health, Labor and Welfare in February 2010, and the two companies will co-market it.

In June 2010, positive news from Phase III trials of Hematide on anemia in chronic renal failure patients triggered a $30 million milestone payment to development partner Affymax. Hematide was touted as an Epogen/Aranesp-buster, but secondary analyses of the trials indicate mixed results. Still, if they can even snatch up a portion of Amgen’s $5+ billion erythropoietin franchise, both companies will be quite happy.

In Vision

I n the past, Takeda’s mentioned the importance of “Takeda-ism” to its corporate identity. In another “lost in translation” moment, the company says its new strategic plan will rely on a policy known as “the Vision”, to inculcate

  • Innovation based on bold leadership in science and medicine resulting in the discovery, development and delivery of high-quality, differentiated products focused on patient needs.
  • Sustainable growth in corporate value by leveraging core therapeutic areas, and an industry-leading pipeline and product portfolio.
  • A culture based on good corporate citizenship that empowers employees through collaboration, inclusion, trust and timely decision making.

With Actos facing U.S. generic competition by mid-2012, Takeda has to act fast on that Vision thing.

 

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Sales: 13.8 Billion

Headcount: 19,362
Pharma Revenues: $13,84 (+30%/+14%*)
Total Revenues: $15,383 (+27%/+12%*)
Net Income:
$2,344 (-25%/-34%*)
R&D Budget: $4,530 (+87%/+64%*)

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

2008 Top Selling Drugs
Drug Indication Sales (+/-%)
Actos diabetes $3,870 +11%
Prevacid GERD $2,714 +108%
Blopress hypertension $2,303 +18%
Lupron prostate cancer $1,261 +16%

Account for 73% of total pharma sales, down from 74% in 2007.

 

PROFILE

Takeda took a jump up our charts this year, as it incorporated some revenues from TAP (and Millennium, to a lesser extent), its former joint venture with Abbott, which was dissolved last year after a 30-year run. The big boost came with Prevacid revenues, which now go directly to Takeda, more than doubling the company’s take from the previous year. Prevacid’s patent expires in the U.S. late in 2011, while the basic version of its top seller, diabetes drug Actos, expires earlier that year. In constant currency, Actos’ sales slipped slightly in 2008, but U.S. revenues from all Actos products were up nearly 8% to $3.0 billion.

Acquisition News

Target: IDM Pharma

Price: $67 million

Announced: May 2009

What they said: “We envisage that [MEPACT, IDM’s osteosarcoma drug] will become a key driver in enhancing our European oncology franchise.”—company statement

Takeda was hoping to smooth out the valley of Actos’ expiration by marketing a combo of Actos and the company’s DPP-IV inhibitor, alogliptin. At the very least, it was hoping to get alogliptin on the market by itself, in order to make some headway into the Type 2 diabetes market, but the company received not-so-good news from U.S. and EU regulators on the project. In March 2009, the FDA informed Takeda that, despite submitting alogliptin’s NDA in December 2007, it would still be subject to a new guidance of CV risk for Type 2 diabetes treatments that was issued one year later. That led the FDA to request an additional Phase III trial of alogliptin.

The company will also conduct a long-term Phase III trial of alogliptin in Europe, pitting it against glipzide (Glucotrol), pushing the expected submission of the MAAs of the DPP-IV inhibitor and the Actos-combo from mid-2009 to sometime in 2012. The FDA decision likely won’t come till 2013. So that’s not good.

Still, the company did get FDA approval of an Actos/metformin XR combo in May 2009, so it will be able to expand its Actoplus Met franchise in that field while negotiating alogliptin’s submissions. In addition, two of the drugs from the TAP pipeline, Kapidex (GERD) and Uloric (hyperuricemia in gout) received FDA approval in 2009.

The integration of TAP has given Takeda has a ready-built U.S. infrastructure, and the company has continued its expansion efforts last year by establishing operations in Canada and boosting sales and marketing forces in several European markets. But with all of its new branches, the company has had to reorganize its executive structure, creating new roles of chief scientific officer, chief administration officer, and executive vice president of international operations. We’ll see if it helps Takeda achieve its goal of becoming a global pharmaceutical company.

 


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Sales: 10.6 Billion

Headcount 15,717
Year Established 1781
Pharma Revenues $10,626 +8%
Total Revenues $12,071 +8%
Net Income $3,121 +9%
R&D Budget $2,421 +46%

 

Top Selling Drugs
Drug Indication Sales (+/-%)
Actos diabetes $3,479 +21%
Blopress antihypertensive $1,959 +11%
Prevacid GERD $1,306 +1%
Lupron prostate cancer $1,089 flat

Account for 74% of total pharma sales, up from 72% in 2006.

 

PROFILE

Takeda is the biggest of the Japanese companies on our Top 20 list, despite slipping back one spot this year. All four of the companies — Takeda, Eisai, Astellas and Daiichi Sankyo — are pursuing strategies to diversify out of the Japanese market, but Takeda’s appears to be the broadest.

In February 2008, Takeda signed a big licensing deal with Amgen, buying out their Japan-based JV and licensing as many as 13 compounds for the Japanese market, while also co-developing a drug worldwide. The JV was converted to Takeda Bio Development.

A month later, the company bought out its U.S. joint venture with Abbott, giving up Lupron, retaining Prevacid and some pipeline products, and most importantly, retaining the sales infrastructure.

Before the ink was dry on that deal, Takeda offered a staggering $8.8 billion to acquire Millennium Pharmaceuticals. Millennium posted record revenues of $528 million in 2007 on sales, royalties, and alliance milestones related to anti-cancer drug Velcade. (Ironically, Japanese rights to Velcade are owned by Janssen/J&J, not Millennium.)

Acquisition News

Target: Millennium Pharmaceuticals
Price: $8.8 billion
Announced: April 2008
What they said: “Millennium greatly strengthens Takeda’s global oncology portfolio, led by the flagship product Velcade, and further enhances its pipeline with clinically differentiated, high-quality product candidates.”
—Yasuchika Hasegawa, president, Takeda

Why all the big moves? Price cuts in Japan are forcing all of its major players to look at new models — Eisai recently bought MGI Pharma for $3.9 billion to build a cancer pipeline; while Daiichi Sankyo just ponied up $4.6 billion to jump into the generics field (and gain market share in India) by buying Dr. Reddy’s, and Astellas spent $380 million to buy Agensys and its antibody R&D expertise — but Takeda’s move is also driven by looming patent expirations (Prevacid in 2009 and Actos in 2011) and the hit that Actos took when it and Avandia were “black boxed” by the FDA last year.

To its credit, Takeda looks like its interest in Millennium is bigger than just Velcade. The company is actively wooing Millennium personnel to stay on, to retain the spirit of the company. Given the number of times we’ve seen companies bought and gutted for their pipelines, this is a refreshing change. (See AstraZeneca’s profile for more on this phenomenon.)

Still, that $8.8 billion bid was eye-popping. I can’t tell if it’s a sign of how foreign companies will be able to use the weak dollar to their advantage in M&As, or more of a sign about how desperate Takeda is to go global.

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