Takeda Pharmaceutical 2021: Coming into view

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Entyvio, Takeda

Through the course of the COVID pandemic, the Takeda that company leaders imagined before acquiring Shire has begun to take shape. 

By Joshua Slatko • [email protected]

 

Takeda Pharmaceutical

1-1, Nihonbashi-Honcho 2-Chome

Chuo-ku, Tokyo 103-8668, Japan

Telephone: +81-3-3278-2111

Website: takeda.com

 

OUTCOMES CREATIVITY INDEX SCORE: 6

Manny Awards — 5 

Cannes Lions — N/A

Clio Health — N/A

Creative Floor Awards — N/A

MM+M Awards — 1 

One Show — N/A 

 

Financial Performance

(All sales are in millions of dollars and were translated using the
Federal Reserve Board’s average rate of exchange in March 2021: ¥108.6991. Takeda’s fiscal year runs from April 1 through March 31. Takeda’s fiscal first quarter runs from April 1 through June 30.)

2020  

Revenue $29,419 

Net income $3,461 

Diluted EPS $2.20  

R&D expense $4,194  

1Q 2021 

Revenue $8,736  

Net income $1,267 

Diluted EPS $0.80 

R&D expense $1,127  

 

Best-Selling Products

(All sales are in millions of dollars and were translated using the Federal Reserve Board’s average rate of exchange in March 2021: ¥108.6991. Takeda’s fiscal year runs from April 1 through March 31. Takeda’s fiscal first quarter runs from April 1 through June 30.)

2020  

Entyvio $3,949  

Immunoglobulin $3,081  

Vyvanse/Elvanse $2,498  

Advate $1,182  

Velcade $930  

Leuplin/Enantone $878  

The orally administered multiple myeloma drug Ninlaro picked up some of Velcade’s slack during the pandemic, with sales growth of 12.7 percent to $804 million during FY 2020.

Ninlaro $804 

Takhzyro $798 

Takecab-F $780  

Azilva-F $756  

Trintellix $634  

Elaprase $633  

Gattex/Revestive $594  

Adcetris $546 

Adynovate/Adynovi $535  

Nesina/Vipidia-F $531  

Albumin $530 

Dexilant $512  

1Q 2021 

Entyvio $1,153  

Immunoglobulin $751 

Vyvanse/Elvanse $729  

Advate $282  

Velcade $277 

Leuplin/Enantone $241  

Takhzyro $235  

Ninlaro $224 

Takecab-F $223  

Azilva-F $208  

Elaprase $171  

Gattex/Revestive $167 

Trintellix $164  

Albumin $163  

Adcetris $158  

Adynovate/Adynovi $141  

Replagal $129  

 

 

“Over the course of FY2020, Takeda remained resilient as we operated in new ways through the COVID-19 pandemic,” said Takeda CEO and President Christophe Weber in the company’s end-of-year statement. “This is a testament to the dedication of our employees, and Takeda’s unwavering commitment to serving patients, our people, and the planet to bring better health for people and a brighter future for the world.”

The new Takeda is coming into view. During the company’s 2020 fiscal year and the first quarter of fiscal 2021, Takeda has continued to trim the fat, divesting a long list of non-core assets and using the proceeds to pay down debt from the Shire acquisition. After reaching a peak of 4.7 in March 2019, Takeda’s debt to adjusted EBITDA ratio had declined to 3.3 as of the end of June. At the same time, some of the big product names that joined the portfolio in the Shire acquisition are beginning to pay substantial dividends, with sales of the immunoglobulin family passing $3 billion for the first time and Takhzyro enjoying growth of more than a quarter in FY 2020. Best of all, the company’s top line, after dipping slightly during FY 2020, appears to be moving back upwards based on the results of the first quarter of FY 2021 as several products are recovering from the effects of the COVID pandemic. 

“Over the course of FY2020, Takeda remained resilient as we operated in new ways through the COVID-19 pandemic,” said Takeda CEO and President Christophe Weber in the company’s end-of-year statement. “This is a testament to the dedication of our employees, and Takeda’s unwavering commitment to serving patients, our people, and the planet to bring better health for people and a brighter future for the world. We maintained business continuity, ensured patient access to our medicines and safeguarded the health and well-being of our employees while helping to address the pandemic.”

Takeda’s top-line revenue in FY 2020 was $29.42 billion, a decline of 2.8 percent compared with the previous year. The company’s net income, though, rose by nearly nine times, from $407 million to $3.46 billion, and earnings per share were up by $1.94 to $2.20. This was in large part due to one-time expenses due to the Shire acquisition and other restructuring activities during FY 2019. According to company leaders, Gastroenterology and Plasma-Derived Therapies Immunology contributed to positive revenue growth; however, this was offset by intensified competition and generic erosion in Rare Diseases and the negative impact across the portfolio from changes in foreign exchange rates. In the first quarter of FY 2021, Takeda’s top-line revenue rose 18.4 percent to $8.74 billion, with net income up by more than two-thirds to $1.27 billion and EPS rose 32 cents to $0.80. 

Partnerships & Acquisitions

During January, Takeda announced the completion of the company’s previously announced sale of a portfolio of select products sold in Latin America to Hypera SA for a total value of $825 million. The divested portfolio includes select over-the-counter and prescription pharmaceutical products sold in Brazil, Mexico, and other South American, Central American and Caribbean countries, which are part of Takeda’s Growth & Emerging Markets Business Unit (GEM BU). Close to 300 Takeda commercial employees transitioned with the divested portfolio at close. As part of a manufacturing and supply agreement, Takeda continues to exclusively manufacture the divested products.

Also in January, Takeda announced the completion of its previously announced sale of a portfolio of select prescription products to Cheplapharm for a total value of $562 million. The portfolio includes 16 prescription pharmaceutical products sold predominantly in Europe which is part of Takeda’s Europe and Canada Business Unit. The divested portfolio comprises non-core prescription pharmaceutical products in a variety of therapeutic categories that includes Cardiovascular/Metabolic and Anti-Inflammatory products along with Calcium.

During February, Takeda announced completion of the previously announced sale of TachoSil Fibrin Sealant Patch to Corza Health Inc. for $399 million. TachoSil is a surgical patch trusted by medical professionals globally to deliver safe, fast, and reliable bleeding control. Under the terms of the transaction, Corza has acquired the assets and licenses that support the development and commercialization of TachoSil, while Takeda maintains ownership of the manufacturing facility in Linz, Austria. Takeda has entered into a long-term manufacturing and supply agreement, under which it will continue to exclusively manufacture TachoSil products and supply them to Corza.

In March, Takeda announced the exercise of its option to acquire Maverick Therapeutics Inc., a private biopharmaceutical company pioneering conditionally active bispecific T-cell targeted immunotherapies. Under the agreement, Takeda will obtain Maverick’s T-cell engager COBRA platform and a broad development portfolio, including Maverick’s lead development candidate TAK-186 (MVC-101) currently in a Phase I/II study for the treatment of EGFR-expressing solid tumors, and TAK-280 (MVC-280), which is anticipated to enter the clinic in the second half of Takeda’s fiscal year 2021 for the treatment of patients with B7H3-expressing solid tumors.

The acquisition followed a multi-year collaboration between Takeda and Maverick signed in 2017 to develop conditionally active T-cell engager therapies, in which Takeda received an equity stake and an exclusive right to purchase Maverick after five years. Based on the success of the lead programs and the promise of the COBRA platform, Takeda exercised its option to acquire Maverick for a pre-negotiated upfront payment as well as potential development and regulatory milestones totaling up to $525 million, subject to certain adjustments, including for Takeda’s current equity stake and Maverick debt.

That same month, Takeda and Ovid Therapeutics Inc., a biopharmaceutical company committed to developing medicines that transform the lives of people with rare neurological diseases, entered into an exclusive agreement under which the company would secure global rights at closing from Ovid to develop and commercialize the investigational medicine soticlestat (TAK-935/OV935) for the treatment of developmental and epileptic encephalopathies, including Dravet syndrome and Lennox-Gastaut syndrome.

Discovered at Takeda’s Shonan, Japan research center, soticlestat is a potent, highly selective, first-in-class inhibitor of the enzyme cholesterol 24-hydroxylase (CH24H). Under the new exclusive agreement, all global rights to soticlestat have been secured by Takeda from Ovid. Takeda assumed sole responsibility for further worldwide development and commercialization, and Ovid no longer has any financial obligation to Takeda under the original collaboration agreement, including for milestone payments or any future development and commercialization costs. Ovid received an upfront payment of $196 million at closing and is eligible to receive up to an additional $660 million upon achieving development, regulatory and sales milestones. In addition, Ovid will receive tiered royalties beginning in the low double-digits and up to 20 percent on sales of soticlestat, if approved and commercialized. Under the 2017 collaboration agreement, Takeda received equity in Ovid and was eligible to receive up to $85 million in payments for regulatory milestones, including the initiation of Phase III clinical trials. Ovid led global development of soticlestat through the successful demonstration of proof-of-concept in multiple rare epilepsies.

Also in March, Takeda announced the completion of the previously announced sale of Takeda Consumer Healthcare Co. Ltd. to Oscar A-Co KK, a company controlled by funds managed by The Blackstone Group Inc. and its affiliates for a total value of $2.23 billion. The divested portfolio included a variety of over-the-counter medicines and health products that generated total revenue of more than $552 million in fiscal year 2019. TCHC’s strong regional brands included Alinamin, its top selling product and Japan’s first vitamin B1 preparation, and Benza, a cold remedy.

Also in March, Takeda announced the completion of its previously-announced sale of a portfolio of select products to Orifarm Group for a total value of up to $670 million. The portfolio includes about 130 over-the-counter and prescription pharmaceutical products sold in Europe, and two manufacturing sites located in Denmark and Poland.

The divested portfolio includes OTC products and food supplements, plus select products within the Cardiovascular, Anti-inflammatory, Respiratory, and Endocrinology therapeutic areas, primarily sold in Denmark, Norway, Belgium, Poland, Finland, Sweden, the Baltics, and Austria. The portfolio generated FY2020 net sales of about $240 million, driven by sales of cough/cold and vitamin OTC brands, along with prescription products such as Warfarub and Levaxin, and other strong regional brands.

Takeda and Orifarm have also entered into manufacturing and supply agreements under which Takeda will continue to manufacture select products on behalf of Orifarm. In addition, about 600 employees from the manufacturing sites, sales and marketing professionals and others supporting the divested portfolio and manufacturing sites have transitioned to Orifarm.

In April, Takeda completed the asset transfer associated with a portfolio of select non-core products in Japan to Teijin Pharma Ltd. The portfolio divested to Teijin Pharma comprised four non-core type 2 diabetes products (Nesina, Liovel, Inisync, and Zafatek) sold in Japan, which generated total sales of about $283 million in FY2019. While the products included in the asset transfer continue to play important roles in meeting patient needs in the country, they were outside of Takeda’s chosen business areas – Gastroenterology, Rare Diseases, Plasma-Derived Therapies, Oncology, and Neuroscience – core to its global long-term growth strategy. 

Takeda and Teijin Pharma have entered into a manufacturing and supply agreement and distribution agreement, under which Takeda will continue to manufacture the products, supply them and provide the distribution channel to Teijin Pharma. Takeda will, for the time being, continue holding the marketing authorizations of the transferred brands, and the timing of the transfer of the marketing authorizations will be determined later.

In July, Takeda and Frazier Healthcare Partners announced a collaboration to launch HilleVax Inc., a biopharmaceutical company to develop and commercialize Takeda’s norovirus vaccine candidate. Takeda has granted a license to HilleVax for the exclusive development and commercialization rights to its norovirus vaccine candidate, HIL-214 (formerly TAK-214), worldwide outside of Japan, in exchange for upfront consideration, as well as future cash milestones and royalties on net sales. Takeda will retain commercialization rights in Japan and HilleVax will integrate certain Japan development activities into its global development. Takeda remains committed to vaccines, and this collaboration allows Takeda to focus its global resources on dengue, COVID-19, pandemic influenza, and Zika, in addition to the vaccines the company distributes in Japan.

HIL-214, which is a virus-like particle based vaccine candidate, completed a randomized, placebo-controlled Phase IIb field efficacy study in 4,712 adult subjects in which HIL-214 was well-tolerated and demonstrated clinical proof of concept in preventing moderate-to-severe cases of acute gastroenteritis from norovirus infection. The candidate has been studied in nine human clinical trials with safety data from more than 4,500 subjects and immunogenicity data from more than 2,000 subjects. 

In September, Takeda entered into an agreement to divest a selection of non-core products from the company’s portfolio sold in Argentina, Colombia, Ecuador, Peru, Guatemala, Costa Rica, Panama, and other countries in Central America and the Caribbean that make up the South Cone, Andean Region, Mexico and Central America and Caribbean regions in its Growth and Emerging Markets Business Unit (GEM BU) to Adium Pharma S.A. The portfolio to be divested includes five non-core products mostly prescription gastroenterology assets including Pantoprazole, Alevian, Dexlansoprazole, Riopan, and Faktu.

Product Performance

Entyvio, for ulcerative colitis and Crohn’s disease, generated nearly $4 billion in sales for Takeda in FY 2020 with growth of 23.6 percent.

Takeda’s leading product, the autoimmune drug Entyvio, earned $3.95 billion in sales for the company in FY 2020, an improvement of 23.6 percent. According to company leaders, this was due to continued exceptional growth through expanded first-line share of gut selective Entyvio in the United States, Europe, and Japan. In the first quarter of FY 2021, sales of Entyvio rose another 23.9 percent to $1.15 billion.

Immunoglobulin, for the treatment of primary immunodeficiency and multifocal motor neuropathy, generated $3.08 billion in sales for Takeda in FY 2020, up 12.1 percent from the previous year, fueled by strong demand and growing supply capabilities. In the first quarter of FY 2021, Immunoglobulin sales declined 4.1 percent to $751 million, due in part to shipment timing.

The Vyvanse/Elvanse franchise, for ADHD, generated sales of $2.5 billion for Takeda in FY 2020, a drop of 0.9 percent. According to company leaders, sales of Vyvanse have been negatively affected by COVID-19, most notably during periods when stay-at-home restrictions were in place reducing patient visits and subsequent diagnoses and creating temporary discontinuation of medication. In the first quarter of FY 2021, sales of Vyvanse bounced back, rising 20 percent to $729 million.

The multiple myeloma drug Velcade has followed a similar pattern as Vyvanse of late, with a sales decline of 14.5 percent to $930 million in FY 2020 and a rebound of 24.6 percent to $277 million in the first quarter of FY 2021. According to Takeda executives, the fiscal first-quarter 2021 performance reflected a rebound in demand after lower sales in the same period of the prior year when prescribers favored orally administered products over infusions or injections, as a result of the COVID-19 outbreak. Ninlaro, an orally administered multiple myeloma drug, enjoyed the upside to Velcade’s downside, with 12.7 percent growth to $804 million in sales in FY 2020 and 6.3 percent growth to $224 million in sales in first-quarter FY 2021. 

Takhzyro, indicated for the treatment of hereditary angioedema, is closing in on blockbuster status for Takeda, with sales of $798 million in FY 2020 and $235 million in the first quarter of FY 2021.

Sales of the hereditary angioedema product Takhzyro enjoyed an impressive bounce in FY 2020, jumping by 27 percent to $798 million. According to company leaders this was primarily due to new launches including prefilled syringe administration in Europe. In the first quarter of FY 2021, sales of Takhzyro rose another 9.6 percent to $235 million.

In August, Takeda announced the publication of the final results from the Phase III HELP (Hereditary Angioedema Long-term Prophylaxis) Study Open-label Extension designed to evaluate the long-term safety (primary endpoint) and efficacy of Takhzyro 300mg every two weeks for up to 2.5 years. The study results showed that preventative treatment with Takhzyro markedly reduced the frequency of hereditary angioedema attacks in patients 12 years of age and older who received treatment for a mean duration of almost 2.5 years (29.6 months; 8.2 standard deviation).

Secondary endpoints of the study showed the mean HAE attack rate observed in the study population was reduced by 87.4 percent overall versus baseline, and attacks requiring acute treatment were reduced by 93.4 percent. Reductions were also shown in the rate of moderate or severe attacks (84.3 percent). Patients treated with Takhzyro 300 mg every two weeks reduced the HAE disease burden by being attack-free for a mean of 97.7 percent of days during treatment, and the average duration of the attack-free period was 14.8 months. Nearly 7 out of 10 patients (68.9 percent) experienced an attack-free period of more than 12 months. 

Takecab, for acid-related diseases, generated $780 million in sales for Takeda in FY 2020, an improvement of 16.7 percent. According to company executives, this increase was driven by the expansion of new prescriptions in the Japanese market due to Takecab’s efficacy in reflux esophagitis and the prevention of recurrence of gastric and duodenal ulcers during low-dose aspirin administration. In the first quarter of FY 2021, sales of Takecab rose another 20.1 percent to $223 million.

The malignant lymphoma drug Adcetris enjoyed solid growth in FY 2020 and the first quarter of FY 2021, helped along by the product’s performance in Japan and China.

Adcetris, for malignant lymphomas, enjoyed sales growth of 12.8 percent to $546 million in FY 2020, reflecting strong growth in sales particularly in Japan where the product has progressively expanded its approved indications in recent years. In first-quarter FY 2021, sales of Adcetris rose another 14.2 percent to $158 million, led by strong growth in sales in the Growth and Emerging Markets, particularly in China where it was approved in May 2020. 

In The Pipeline

In March, Takeda announced the results from a subgroup analysis of the Phase III TAK-620-303 (SOLSTICE) trial, for the investigational drug TAK-620 (maribavir), which supported the efficacy results from the overall randomized population. More than three times as many (62.8 percent) transplant recipients with confirmed genotypic resistant CMV infection at baseline treated with maribavir achieved confirmed CMV viremia clearance at Study Week 8 (end of treatment phase) compared to those treated with conventional antiviral therapies (20.3 percent) (investigator assigned treatment; IAT consists of one or a combination of ganciclovir, valganciclovir, foscarnet, or cidofovir). 

Findings from the overall trial population showed the study met its primary endpoint, demonstrating that maribavir was superior to conventional antiviral therapies in CMV viremia clearance at Study Week 8. Specifically, 55.7 percent of transplant recipients with refractory, with or without resistance (R/R), CMV infection/disease treated with maribavir achieved confirmed CMV viremia clearance as compared to 23.9 percent of those on conventional antiviral therapies.

In May, Takeda announced that its dengue vaccine candidate (TAK-003) demonstrated continued protection against dengue illness and hospitalization, regardless of an individual’s previous dengue exposure, with no important safety risks identified through three years after vaccination in the ongoing pivotal Phase III Tetravalent Immunization against Dengue Efficacy Study (TIDES) trial. TIDES enrolled more than 20,000 healthy children and adolescents ages 4 to 16 years in dengue-endemic countries in Latin America and Asia.

Through three years (36 months after the second dose), TAK-003 demonstrated overall vaccine efficacy of 62.0 percent against virologically confirmed dengue, with 65.0 percent VE in seropositive individuals and 54.3 percent VE in seronegative individuals. TAK-003 also demonstrated 83.6 percent VE against hospitalized dengue, with 86.0 percent VE in seropositive individuals and 77.1 percent VE in seronegative individuals. Observations of varied VE by serotype remained consistent with previously reported results. No evidence of disease enhancement was observed. TIDES safety and efficacy data through 36-months follow-up was included in regulatory submissions to the European Union and dengue-endemic countries and will be part of additional filings planned for 2021, including in the United States.

In June, Takeda presented results from a new subgroup analysis of SOT recipients in the Phase III TAK-620-303 (SOLSTICE) trial, for the investigational drug maribavir. More than twice (55.6 percent) as many SOT recipients with R/R CMV infection at baseline treated with maribavir achieved confirmed CMV viremia clearance at Study Week 8 (end of treatment phase) compared to those treated with conventional antiviral therapies (26.1 percent) (investigator assigned treatment; IAT consists of one or a combination of ganciclovir, valganciclovir, foscarnet, or cidofovir). The results presented showed consistent efficacy in SOT recipients receiving maribavir in heart, lung, and kidney transplants.

More than three times as many lung transplant recipients with R/R CMV infection treated with maribavir achieved confirmed CMV viremia clearance as compared to those on conventional therapies (47.5 percent versus 13.6 percent). More than 1.5 times as many kidney transplant recipients with R/R CMV infection treated with maribavir achieved confirmed CMV viremia clearance as compared to those on conventional therapies (59.5 percent versus 34.4 percent). And 42.9 percent of heart transplant recipients with R/R CMV infection treated with maribavir achieved confirmed CMV viremia clearance as compared to 11.1 percent of those on conventional therapies. Based on the results of SOLSTICE, FDA granted Priority Review status to maribavir in May.

In July, FDA granted Breakthrough Therapy Designation to TAK-994, Takeda’s Phase II investigational oral orexin agonist, which is designed to selectively target orexin 2 receptors. TAK-994 is being studied for treating excessive daytime sleepiness in patients with narcolepsy type 1, a chronic neurological disorder that alters the sleep-wake cycle. EDS is a hallmark symptom of NT1 and is characterized by a person’s inability to stay awake and alert throughout the day, and falling asleep unintentionally or at inappropriate times on a daily basis.

The TAK-994 BTD was based, in part, on early phase and preliminary clinical data that indicates Takeda’s investigational oral orexin agonist may demonstrate substantially improved objective and subjective measurements of daytime wakefulness in NT1 patients. TAK-994 is being studied in an ongoing Phase II (TAK-994-1501) study.

Takhzyro, indicated for the treatment of hereditary angioedema, is closing in on blockbuster status for Takeda, with sales of $798 million in FY 2020 and $235 million in the first quarter of FY 2021.

In September, FDA approved Exkivity (mobocertinib) for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor exon 20 insertion mutations as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy. Exkivity, which was granted priority review and received Breakthrough Therapy Designation, Fast Track Designation, and Orphan Drug Designation by FDA, is the first and only approved oral therapy specifically designed to target EGFR Exon20 insertion mutations. This indication was cleared under Accelerated Approval based on overall response rate and DoR. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. The FDA approval was based on results from the platinum-pretreated population in the Phase I/II trial of Exkivity, which consisted of 114 patients with EGFR Exon20 insertion+ NSCLC who received prior platinum-based therapy and were treated at the 160 mg dose. FDA simultaneously approved Thermo Fisher Scientific’s Oncomine Dx Target Test as an NGS companion diagnostic for Exkivity to identify NSCLC patients with EGFR Exon20 insertions.

Also in September, Takeda announced that the Phase III PANTHER (Pevonedistat-3001) study did not achieve pre-defined statistical significance for the primary endpoint of event-free survival. The trial evaluated whether the combination of pevonedistat plus azacitidine as first-line treatment for patients with higher-risk myelodysplastic syndromes, chronic myelomonocytic leukemia, and low-blast acute myeloid leukemia improved EFS versus azacitidine alone. An event in the trial is defined as death or transformation to AML in participants with higher-risk MDS or CMML, whichever occurs first, and death in participants with AML.