Takeda 2019: An international flavor

 

The acquisition of Shire means that Takeda is as much an American company now as it is Japanese.

 

 

 

 

 

Takeda Pharmaceutical Co.
1-1, Nihonbashi-Honcho 2-Chome
Chuo-ku, Tokyo 103-8668, Japan
Telephone: +81 3 3278-2111
Website: takeda.com

 

Best-Selling Rx Products

Product	FY2018 Sales	FY2017 Sales
Entyvio	$2,422	$1,812
Velcade	$1,151	$1,235
Leuprorelin (Leuplin)	$991	$973
Azilva	$637	$576
Dexilant	$623	$591
Ninlaro	$560	$417
Immunoglobulin*	$560	—
Pantoprozole (Protonix)	$554	$592
Takecab	$524	$436
Trintellix	$518	$435

All sales are in millions of dollars and were translated using the Federal Reserve Board’s average rate of exchange in March 2019: ¥111.1443.

Takeda’s fiscal year runs from April 1 through March 31.

* Acquired in the Shire transaction; results are for January 8, 2019 through March 31, 2019.

 

Financial Performance

	FY2018	FY2017
Revenue	$18,869	$15,930
Net income	$981	$1,680
Diluted EPS	$1.02	$2.14
R&D expense	$3,314	$2,928

	1Q FY2019	1Q FY2018
Revenue	$7,640	$4,047
Net income	($186)	$703
Diluted EPS	($0.12)	$0.90
R&D expense	$1,051	$648

All figures are in millions of dollars except EPS and were translated using the Federal Reserve Board’s average rate of exchange in March 2019: ¥111.1443.

Takeda’s fiscal year runs from April 1 through March 31.

Takeda’s fiscal first quarter runs from April 1 through June 30.

 

Outcomes Creativity Index Score: 22
Manny Awards – 2
Cannes Lions – 5
LIA: Health & Wellness – N/A
Clio Health – N/A
One Show: HW&P – N/A
MM&M Awards – 15
Global Awards – N/A
Creative Floor Awards – N/A

 

 

Takeda is not just a Japanese company any more. As recently as its 2016 fiscal year, the company’s revenue from Japan was 37.8 percent of the total, while U.S. revenue was an even 30 percent. In FY2017, revenue from Japan still accounted for nearly a third of the top line, with the United States accounting for another third. But, helped along by the January 2019 acquisition of Shire, the U.S. piece of the pie rose to 39.5 percent in FY2018 and 49 percent in the first quarter of FY2019 while the Japanese share declined to 27.2 percent and then 17.9 percent. Which, of course, is exactly what Takeda’s leaders had in mind when they set out to acquire Shire. 

“Fiscal 2018 was an important year in the history of Takeda as we completed the acquisition of Shire to create a competitive, values-based, R&D-driven global biopharmaceutical leader,” said Takeda President and CEO Christophe Weber at the end of the fiscal year. “I am delighted to say that throughout the year, while we have focused on planning and executing the integration, we have also maintained strong business momentum, as demonstrated by our excellent financial results. The integration of Shire is progressing as planned, aligned with Takeda’s values and culture. We have also identified opportunities to realize greater cost synergies, and already have made progress on our divestment strategy for non-core assets.”

Takeda’s top-line revenue in FY2018 came in at ¥2,097.2 billion ($18.87 billion), an improvement of 18.4 percent. Company leaders estimated that about ¥309.2 billion ($2.78 billion) of the year-to-year revenue growth came as a result of the Shire acquisition. However, net income declined by 41.7 percent to ¥109 billion ($981 million), and earnings per share were cut by more than half, from ¥237.56 ($2.14) to ¥112.86 ($1.02). This was due in part to the application of the company’s inventory policies to the acquired businesses, which led to a recognition of significant non-cash expenses relating to the unwinding of fair value adjustments to inventory as a component of cost of sales. Takeda also recorded significant intangible assets in connection with the Shire acquisition, which led to an increase in amortization and impairment losses. In the first quarter of FY2019, Takeda’s top-line sales were ¥849.1 billion ($7.64 billion), up 88.8 percent compared with the first quarter of FY2018, while net income was negative ¥20.6 billion (negative $186 million) and loss per share was ¥13.28 ($0.12). However, the company’s core net profit calculation, which leaves out transaction-related costs and other items that management believes are unrelated to core operations, had net profit at ¥198.4 billion ($1.79 billion) for the quarter, an improvement of 103 percent. For full fiscal year 2019, Takeda leaders are projecting a net loss per share of ¥236 ($2.12), with underlying core net earnings per share in the ¥360 ($3.24) to ¥380 ($3.42) range.

Shire acquisition

In January, Takeda announced the completion of its acquisition of Shire plc. According to company leaders, as a result of the transaction Takeda now has an attractive, expanded geographic footprint and leading position in Japan and the United States, bringing its innovative medicines to about 80 countries/regions with dedicated employees worldwide. Takeda’s R&D efforts are focused on its four therapeutic areas of Oncology, Gastroenterology, Neuroscience, and Rare Diseases, with targeted R&D investment also committed to Plasma-Derived Therapies and Vaccines. Takeda’s strengthened innovative R&D engine, leaders say, enables the company to have a more global, robust and modality-diverse pipeline as well as to focus on breakthrough innovation. The combined annual revenue of the new company, exceeding $30 billion, is mainly derived from the key business areas of Oncology, GI, Neuroscience, Rare Diseases, and PDT.

“We are delighted that the acquisition was approved by an overwhelming majority of our shareholders at Takeda’s extraordinary general meeting on December 5th, 2018,” Weber said upon the deal’s completion. “We are also pleased to have completed the acquisition several months earlier than expected, which was enabled through the hard work of our respective organizations and the smooth receipt of regulatory clearances. We appreciate the support of our employees, partners and shareholders throughout the process. This marks a significant moment in Takeda’s history and is an exciting step forward as we accelerate our transformation journey to deliver highly innovative medicines to patients around the world with expanded scale and geographical footprint.”

Other acquisitions and partnerships

In January, Takeda announced multiple new research collaborations in immuno-oncology, an area of key strategic focus for the company. Through these collaborations, company leaders say, 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 treating multiple myeloma, acute myeloid leukemia and additional solid tumor indications. The broad, multi-faceted collaboration is co-led by CAR-T therapy pioneer Michel Sadelain, M.D., Ph.D., Director of the Center for Cell Engineering at MSK and scientific founder of Juno Therapeutics.

Additionally, Takeda exercised an option under its existing research collaboration with Noile-Immune Biotech Inc., which originated in September 2017. Due to the success of the collaboration, Takeda has 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. The company plans to gain regulatory approval for human testing of NIB-102 by the end of this year.

Also, the exercised option for an exclusive oncology-targeted Humabody license from Crescendo Biologics will allow Takeda to evaluate these Humabody VHs for the development of novel CAR-T therapeutics. Management says the development will take advantage of the unique properties of single-domain tumor-targeted binders as an alternative to conventional single-chain variable fragment (scFv)-based approaches.

In May, Takeda entered into an agreement to sell TachoSil, a surgical patch designed to achieve safe, fast and reliable bleeding control, to Ethicon for about $400 million. Upon close, about 80 employees will transition to Ethicon. Takeda recorded full-year adjusted net sales for TachoSil of about $155 million in the fiscal year ended March 31, 2018. Under the terms of the agreement, upon close, Ethicon will acquire the assets and licenses that support the manufacturing, licensing and commercialization of TachoSil, while Takeda will maintain ownership of the manufacturing facility in Linz, Austria. Takeda has entered into a long-term manufacturing services agreement, under which it will continue to manufacture TachoSil products and supply them to Ethicon.

In June, Takeda announced the completion of the company’s sale of Xiidra (lifitegrast ophthalmic solution) to Novartis for $3.4 billion upfront in cash and up to an additional $1.9 billion in potential milestone payments. Adjusted net sales for Xiidra in the most recent fiscal year were $388 million. Takeda intends to use the proceeds from the sale to reduce its debt and accelerate deleveraging toward its target of 2x net debt/adjusted EBITDA in the medium term following closing of the Shire acquisition. As of March 31, 2019, Takeda had 5,048.9 billion yen in net debt outstanding and its net debt/adjusted EBITDA ratio was 4.7x. Takeda continues to target a net debt/adjusted EBITDA ratio of 2x within three to five years. Xiidra is the first prescription treatment approved by FDA for both signs and symptoms of dry eye disease, with a mechanism of action that targets inflammation.

In July, Takeda and Pfizer Japan Inc. announced the termination of co-promotion for the rheumatoid arthritis/juvenile idiopathic arthritis treatment Enbrel, scheduled at the end of November 2019.

Enbrel 25 milligrams for subcutaneous injection was launched in Japan in March 2005, and Pfizer and Takeda have co-promoted the medicine under a co-promotion agreement. Enbrel was launched in syringe-type in June 2008 and in pen-type in June 2013, offering various doses and dosage types to meet the needs of patients with rheumatoid arthritis and juvenile idiopathic arthritis, as well as those of medical personnel. Takeda and Pfizer have to date been working together to promote the proper use of the drug.

As a result of discussions between the two companies prompted by changes in the business environment, the co-promotion will be terminated by the end of November 2019. From December 2019, Enbrel will be promoted solely by Pfizer. However, Takeda will be responsible for distribution until the end of March 2020. What happens after that remains under discussion.

Product performance

The autoimmune product Entyvio was Takeda’s top seller in the fiscal year ending March 31, 2019 with total sales of ¥269.2 billion ($2.42 billion), an improvement of 33.7 percent over the previous fiscal year. According to company leaders, this was attributable to Entyvio’s steady expansion of patient share in the bio-naive segment. Entyvio also received a new indication approval in Japan in July 2018 for the treatment of patients with moderately to severely active ulcerative colitis; the company subsequently launched the new indication in November 2018. In the first quarter of Takeda’s FY2019, sales of Entyvio rose 36.9 percent to ¥83.9 billion ($755 million).

In March, Takeda announced results from the Phase IIIb head-to-head VARSITY study which demonstrated that the gut-selective biologic vedolizumab (Entyvio) was superior to the anti-tumor necrosis factor-alpha biologic adalimumab (Humira) in achieving clinical remission in patients with moderately to severely active ulcerative colitis at week 52. Data showed that 31.3 percent of patients receiving vedolizumab intravenous achieved the primary endpoint of clinical remission compared to 22.5 percent of patients treated with adalimumab subcutaneous at week 52, with the difference being statistically significant.

Furthermore, treatment with vedolizumab was associated with significantly higher rates of mucosal healing at week 52, with 39.7 percent of patients receiving vedolizumab achieving mucosal healing compared to 27.7 percent treated with adalimumab. A non-statistically significant difference in favor of adalimumab was seen in the percentage of patients using oral corticosteroids at baseline who discontinued corticosteroids and were in clinical remission at week 52. While the study was not powered to compare the safety of the two biologics, patients treated with vedolizumab (62.7 percent) had a lower rate of overall adverse events over 52 weeks than patients treated with adalimumab (69.2 percent), with a lower rate of infections reported in patients treated with vedolizumab (33.5 percent) as compared to adalimumab (43.5 percent). The rate of serious adverse events was also lower in vedolizumab-treated patients than adalimumab (11.0 percent versus 13.7 percent respectively).

In May, Japan’s the Ministry of Health, Labour and Welfare approved an additional indication for Entyvio for the treatment of adult patients with moderately to severely active Crohn’s disease. The application filing for this new indication submitted to the MHLW in July 2018 included data from Study CCT-001, a multicenter, randomized, double-blind, placebo-controlled, parallel-group Phase III clinical trial investigating the efficacy, safety and pharmacokinetics of vedolizumab induction and maintenance treatment involving 157 Japanese patients with moderately to severely active CD, in addition to data from the global GEMINI 2 and 3 trials involving 1,115 and 416 patients respectively.

In the CCT-001 study, the vedolizumab group exceeded the placebo group (26.6 percent versus 16.7 percent) in terms of the percentage of CDAI-100 improvement (≥100-point decrease in the CDAI score), which was a primary endpoint of the induction period; however, the difference was not statistically significant. The proportion of patients in remission at Week 60 (CDAI score less than 150 points), which was a primary endpoint, were 41.7 percent in the vedolizumab group and 16.7 percent in the placebo group. Primary and secondary endpoint results in the induction and maintenance period showed broadly the same trends as seen in the GEMINI II and III trials.

Also in May, Takeda announced further results from the Phase IIIb head-to-head VARSITY study, which demonstrated that Entyvio was superior to adalimumab (Humira) in achieving clinical remission at week 52 in patients with moderately to severely active ulcerative colitis. New exploratory data showed that a greater proportion of patients receiving vedolizumab intravenous achieved clinical response at week 14 compared to those treated with adalimumab subcutaneous, 67.1 percent versus 45.9 percent respectively. A separation between the treatment groups was seen as early as week 6, favoring vedolizumab.

In July, Takeda announced top-line results from the VISIBLE 2 clinical trial evaluating the efficacy and safety of an investigational subcutaneous formulation of the gut-selective biologic vedolizumab as maintenance therapy in adult patients with moderately to severely active Crohn’s disease who achieved clinical response at week 6 following two doses of open-label vedolizumab intravenous therapy at weeks 0 and 2. In evaluating the primary endpoint of the trial, a statistically significant proportion of patients receiving vedolizumab SC achieved clinical remission at week 52 compared to placebo. Patients received vedolizumab SC beginning at week 6 and every 2 weeks up to week 50.

VISIBLE 2 is a Phase III, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of vedolizumab SC as maintenance therapy in patients with moderately to severely active CD. The study enrolled 644 participants, all of whom had an inadequate response with, loss of response to, or intolerance to corticosteroids, immunomodulators, or tumor necrosis factor-alpha (TNFα)-antagonist therapy prior to being enrolled. Patients who achieved clinical response at week 6, following two doses of open-label vedolizumab 300 milligrams IV therapy at weeks 0 and 2, were randomized into one of two treatment groups, vedolizumab 108 milligrams SC or placebo SC. Both treatment groups received a subcutaneous injection every two weeks starting at week 6 up to week 50.

In August, Takeda submitted a New Drug Application to the Ministry of Health, Labour and Welfare in Japan for a subcutaneous formulation of vedolizumab for maintenance therapy in adults with moderately to severely active ulcerative colitis. Takeda proposes to make vedolizumab SC available in both syringe and pen options. A similar application was accepted for review by FDA in May; an application for maintenance therapy in both UC and Crohn’s was accepted by the European Medicines Agency in April.
The NDA filing was based on the results of the VISIBLE 1 trial, a Phase III clinical trial that evaluated the efficacy and safety of vedolizumab subcutaneous as maintenance therapy.

In the VISIBLE 1 trial conducted in 216 adult patients with moderately to severely active ulcerative colitis, clinical response was obtained at week 6 following two doses of open-label intravenous administrations of vedolizumab as an induction therapy at weeks 0 and 2.

In evaluating the primary endpoint of VISIBLE 1, a statistically significant proportion of patients receiving vedolizumab subcutaneous 108 milligrams maintenance therapy administered every two weeks achieved clinical remission compared to patients receiving placebo (46.2 percent versus 14.3 percent) at week 52. A similar rate of clinical remission was observed in the vedolizumab intravenous 300 milligrams reference arm (42.6 percent) at week 52.

Velcade, indicated for the treatment of multiple myeloma, generated sales of ¥127.9 billion ($1.15 billion) in FY2018, a decline of 6.9 percent. This was due to a loss of market exclusivity in the United States in the previous year. In the first quarter of FY2019 sales of Velcade increased by 1 percent to ¥31.7 billion ($285 million).

Takeda’s other multiple myeloma product Ninlaro is moving towards superseding Velcade in the company’s portfolio. Ninlaro brought in sales of ¥62.2 billion ($560 million) in FY2018, an improvement of 33.9 percent. Strong performance in several regions, particularly in the United States, contributed to this growth. Sales of Ninlaro in the first quarter of FY2019 were ¥18.3 billion ($165 million), 30.8 percent better than the first quarter of FY2018.

In June, Takeda announced that the Phase III TOURMALINE-AL1 clinical trial in patients with relapsed or refractory systemic light-chain amyloidosis did not meet the first of two primary endpoints. Treatment with Ninlaro in combination with dexamethasone did not demonstrate a significant improvement in overall hematologic response compared to standard of care regimens. As a result of this analysis, Takeda has decided to discontinue the study.

Immunoglobulin, the best-selling product group from Shire’s portfolio, was responsible for ¥62.2 billion ($560 million) in sales for Takeda from the date of acquisition (January 2019) in FY2018. In Shire’s final reported full year of operations, immunoglobulin products generated $2.48 billion in sales, a 10.9 percent improvement over the previous year.
In the first quarter of FY2019, immunoglobulin sales were ¥68 billion ($612 million), identical with Shire’s results in the corresponding second quarter of 2018. Takeda’s immunoglobulin products are antibody replacements to treat patients with primary immunodeficiencies.

The acid blocker Takecab generated ¥58.2 billion ($524 million) in sales for Takeda in FY2018, an improvement of 20.1 percent. According to company leaders, this was attributed to expansion of new prescriptions in the Japanese market due to Takecab’s efficacy in reflux esophagitis and the prevention of recurrence of gastric ulcers during low-dose aspirin administration. Sales of Takecab in the first quarter of FY2019 were ¥18.3 billion ($165 million), up 28.1 percent compared with 1Q FY2018.

Trintellix, for major depressive disorder, was responsible for ¥57.6 billion ($518 million) in sales in FY2018, an improvement of 19 percent. Takeda says the increase was due to prescribers and patients increasingly making Trintellix part of their comprehensive approach to treating major depressive disorder. In first-quarter FY2019, Trintellix sales totaled ¥17.4 billion ($157 million), up 23.4 percent compared with the first quarter of FY2018.

In the pipeline

In January, Takeda announced that the pivotal Phase III trial of its dengue vaccine candidate met the primary efficacy endpoint. This first analysis of the Tetravalent Immunization against Dengue Efficacy Study (TIDES) trial showed that the company’s investigational live-attenuated tetravalent dengue vaccine TAK-003 was efficacious in preventing dengue fever caused by any of the four serotypes of the virus. While review of the extensive data set is ongoing, TAK-003 was well tolerated with no significant safety concerns to date. The TIDES trial is continuing and additional results are expected later this year, along with results from other Phase III studies.

The double-blind, randomized and placebo-controlled Phase III TIDES trial is evaluating the safety and efficacy of two doses of TAK-003 in the prevention of laboratory-confirmed symptomatic dengue fever of any severity and due to any of the four dengue virus serotypes in children and adolescents. Study participants were randomly assigned to receive either TAK-003, 0.5 mL or placebo, by subcutaneous injection on Day 1 and Day 90. The study comprises three parts. The current analysis, Part 1, evaluated vaccine efficacy and safety through 15 months after the first dose. Part 2 continues for an additional six months to complete the assessment of the secondary endpoints of VE by serotype, baseline serostatus and severity. Part 3 evaluates VE and long-term safety by following participants for an additional three years. The Part 1 and Part 2 data will form the basis for filing for licensure.

The trial is taking place at sites in dengue-endemic areas in Latin America (Brazil, Colombia, Panama, Dominican Republic, and Nicaragua) and Asia (Philippines, Thailand, and Sri Lanka) where there are unmet needs in dengue prevention and where severe dengue is a leading cause of serious illness and death among children. Baseline blood samples were collected from all individuals participating in the trial to allow for evaluation of safety and efficacy based on serostatus. Takeda and an independent Data Monitoring Committee of experts are actively monitoring safety on an ongoing basis.

In February, the European Commission extended the current marketing authorization of Adcetris (brentuximab vedotin) to include treatment of adult patients with previously untreated CD30+ Stage IV Hodgkin lymphoma in combination with AVD (Adriamycin, vinblastine, and dacarbazine). Adcetris is an antibody-drug conjugate directed at CD30, a defining marker of Hodgkin lymphoma.

The approval was based on the results of the randomized, open-label, two-arm, multi-center Phase III ECHELON-1 study designed to compare Adcetris plus AVD to ABVD (Adriamycin, bleomycin, vinblastine, and dacarbazine) as a therapy in adult patients with previously untreated Hodgkin lymphoma. The trial achieved its primary endpoint resulting in a statistically significant improvement in modified progression-free survival versus the control arm, which corresponds to a 23 percent reduction in the risk of progression, death, or need for additional anticancer therapy. Key subgroup analyses showed a larger effect in patients with Stage IV Hodgkin lymphoma in the Adcetris plus AVD arm versus the control arm.

Also during February, Takeda announced results from its phase IIIb/IV clinical trial for Adynovate [Antihemophilic Factor (Recombinant), PEGylated]. The PROPEL study is a PROspective, randomized, multi-center study comparing the safety and efficacy of Adynovate following PK-guided prophylaxis targeting two different Factor Eight (FVIII) trough Levels in subjects with severe hemophilia A.

The study showed that Adynovate prophylaxis targeting 8–12 percent (HIGH) vs 1–3 percent (LOW) trough levels was associated with a trend toward a higher proportion of patients with a total annualized all bleed rate=0 (66 percent HIGH versus 39 percent LOW). The HIGH group was also associated with a trend toward a lower total ABR, as well as a higher proportion of patients with all annualized joint bleed rate=0 (90 percent HIGH versus 68 percent LOW) and all spontaneous ABR=0 (84 percent HIGH versus 61 percent LOW). The data suggests that optimizing FVIII profiles through PK-driven dosing that targets trough levels 8-12 percent was consistently achievable and further treatment personalization for patients with hemophilia A should be considered. Safety profiles were comparable and consistent with previous Adynovate trials. Ongoing analyses will characterize the relationship between PK-tailored dosing of Adynovate FVIII levels and bleeding events.

In June, Takeda announced new data from an ad-hoc analysis of the Phase III HELP Study, designed to evaluate the onset of action for Takhzyro (lanadelumab) during days 0-69 of treatment. The analysis suggests that Takhzyro starts to prevent hereditary angioedema attacks during this early treatment phase, with patients experiencing an 80.1 percent decrease in mean monthly attack rate compared to placebo.

The ad-hoc analysis evaluated the efficacy of Takhzyro compared with placebo during days 0-69 of treatment using the same approach that was used to evaluate the primary and secondary endpoints during the complete study period (days 0-182). Results from the analysis showed that in patients receiving the recommended starting dose of Takhzyro 300 milligrams every two weeks, there was a significant reduction in mean monthly attack rate (80.1 percent decrease) compared to placebo. During this initial treatment phase, patients treated with Takhzyro 300 milligrams every two weeks also experienced fewer severe attacks compared to placebo (7.4 percent versus 22 percent) and were more likely to be HAE attack-free compared to those on placebo (48.1 percent versus 7.3 percent).

Across all Takhzyro treatment arms, (300 milligrams every two weeks, 300 milligrams every four weeks, 150 milligrams every four weeks), there was an improvement in mean monthly attack rate, monthly rate of moderate to severe attacks, monthly rate of attacks requiring acute treatment and the number of attack-free days, versus placebo, during the entire study period.

In July, the Center for iPS Cell Research and Application at Kyoto University and Takeda announced that a novel induced pluripotent stem (iPS) cell-derived chimeric antigen receptor T-cell therapy (iCART) has been transferred from their T-CiRA research collaboration to Takeda as the program begins process development toward clinical testing. Under the terms of the T-CiRA agreement, Takeda has the global rights to develop and commercialize the iCART product and CiRA will receive development and approval milestones. The teams will continue to collaborate as they prepare the iCART program for a clinical trial in 2021.

Autologous CAR T-cell therapy is a type of immunotherapy that uses a patient’s own genetically modified T-cells to find and kill cancer cells. Since first-generation autologous CAR-T therapies are created from the blood of each individual patient, development is a slow and expensive process. Developed by CiRA’s Shin Kaneko, M.D., Ph.D., who will remain involved as a Takeda advisor, the iCART program uses a clonal master iPS cell bank to create off-the-shelf CAR-T therapies that can be tailored to each patient on demand. The goal is to develop a process that is scalable – capable of creating very large quantities of homogenous doses from a single master cell bank – and less costly than first generation CAR-Ts. In vivo pre-clinical studies showed robust antitumor efficacy with a CD19-targeted iCART.

T-CiRA was established in 2015 as a 10-year joint research program between CiRA and Takeda. Under the direction of Nobel Laureate Dr. Shinya Yamanaka, Takeda is providing 20 billion yen in collaborative funding and is jointly running multiple projects led by researchers invited from CiRA, and other research institutes. As part of the ongoing collaboration, T-CiRA conducts cutting-edge research in the clinical application of iPS cells in areas including immuno-oncology, heart failure, diabetes mellitus, neuro-psychiatric disorders, and intractable muscle diseases at Takeda’s Shonan Health Innovation Park.

Also in July, Takeda announced updated results from its Phase IIIb/IV clinical trial for Adynovate. The latest results of the landmark PROPEL study showed that Adynovate prophylaxis in severe hemophilia A patients may enhance a patient’s PK profile – by targeting FVIII trough levels of 8–12 percent (elevated prophylaxis arm, ELE) as compared with 1–3 percent (reference prophylaxis arm, REF). This represents a clinically meaningful trend towards more patients experiencing zero bleeds (62 percent ELE versus 42 percent REF, respectively). Patients randomized to the 8-12 percent target group also saw a reduced mean total annualized bleed rate (1.6 ELE versus 3.6 REF, respectively), and a reduced mean spontaneous joint ABR (0.5 ELE versus 2.0 REF).

The data supports the view that patients may benefit from PK-driven dosing that targets FVIII trough levels of 8–12 percent. The safety findings from this latest update were also comparable and consistent with previous Adynovate trials. Ongoing analyses will further characterize the relationship between PK-tailored dosing of Adynovate FVIII levels and bleeding events.