Congenital Thrombotic Thrombocytopenic Purpura

Thanks to the FDA approval, Takeda said it’s looking to reverse a previous impairment loss tied to Eohilia’s FDA rejection in 2021. Eohilia, an oral suspension formulation of the corticosteroid budesonide, has surprisingly won over the FDA even after the drug’s developer, Takeda, had at one point abandoned the program following an FDA rejection. Monday, Takeda announced the FDA’s approval for Eohilia for treating people 11 years and older with the inflammatory disease eosinophilic esophagitis (EoE). This makes Eohilia the first FDA-sanctioned oral med for the condition. In 2022, Sanofi and Regeneron’s injectable Dupixent claimed the title as the first FDA-approved therapy for EoE. “As the treatment needs and goals of patients with EoE can vary, I welcome the flexibility that Eohilia offers as an oral medication,” Ikuo Hirano, M.D., from Northwestern University, an investigator in Eohilia’s clinical trials, said in a statement Monday. Eosinophilic esophagitis is a chronic inflammatory disease that can cause painful damage to the esophagus, resulting in difficulty in swallowing. The condition affects about 1 in 2,000 people in the U.S., and Takeda has estimated Eohilia could reach $300 million to $500 million in peak sales. Eohilia’s approval comes after some twists and turns. After a regulatory delay caused by additional data submissions, the FDA in late 2021 handed Takeda a rejection, blighting Eohilia’s prospect of becoming the very first official EoE drug. After reviewing the FDA’s complete response letter, Takeda realized that the agency wanted data from an additional clinical trial, and that it could not take the drug any further. “After a deep and careful assessment of the evolving treatment landscape in EoE, as well as considerations including operational challenges required for an additional clinical study, we could not justify further Eohilia development,” Takeda’s R&D chief Andy Plump, M.D., Ph.D., said during an investor call at the time. Fast forward to October 2023, when Takeda suddenly said it had refiled Eohilia in the prior month. This time, Plump said “strong data and remaining unmet need in the U.S. spurred significant grassroots support” for Eohilia from the gastrointestinal and EoE communities. Takeda worked with these communities to include additional data around Eohilia’s benefits in the resubmission, he explained. According to Plump’s comment and Eohilia’s current label, Takeda apparently played down findings from a one-year maintenance study and instead focused on the drug’s 12-week data from a phase 3 and a phase 2 trial in its resubmission. Although that strategy got Eohilia the green light from the FDA, it also led to a restriction. In Eohilia’s label, the FDA notes that the drug hasn’t shown to be effective for longer than 12 weeks. The label later points out that in a phase 3 extension study, continued treatment with Eohilia beyond 12 weeks didn’t show a statistically significant improvement versus re-randomization to placebo on some efficacy endpoints. Still, the drug appears to be a good option for 12 weeks of treatment. Between the phase 3 and phase 2 trials, Eohilia, given at 2mg twice daily, respectively helped 53% and 38% patients achieve histological remission after 12 weeks of treatment, versus 1% and 2.4% for those who received placebo. By comparison, Sanofi and Regeneron won Dupixent’s EoE nod with a 24-week analysis showing the weekly antibody drug led to histological remissions in 60% and 59% of patients in two parts of a phase 3 trial, versus 5% and 6% for the placebo group. As for disease symptoms measured by the patient-reported Dysphagia Symptom Questionnaire (DSQ), Eohilia delivered 10.2- and 14.5-point improvements, compared with 6.5- and 5.9-point improvements for placebo. Results on the same endpoint for Dupixent were 21.9 and 23.8 points, versus 9.6 and 13.9 points for placebo. Thanks to the approval, Takeda said it’s looking to reverse a previously recorded impairment loss tied to Eohilia’s rejection, but that it doesn’t expect the impact to be material. Takeda’s business has come under pressure lately after the Japanese pharma’s blockbuster ADHD drug Vyvanse lost U.S. market exclusivity in August. Adding to the woes are a phase 3 flop for the company’s stem cell therapy Alofisel in complex perianal fistulas, the global market withdrawal of EGFR lung cancer med Exkivity, and the voluntary retraction of an application for the dengue vaccine Qdenga in the U.S. The company has recently won two other FDA nods, one for colorectal cancer drug Fruzaqla, which Takeda in-licensed from Hutchmed a year ago; and the other for rare disease therapy Adzynma in congenital thrombotic thrombocytopenic purpura.

In the aftermath of Vyvanse’s loss of exclusivity, Takeda is making bold pledges to investors to get its business back on track. Despite the recent loss of exclusivity on Takeda's attention-deficit/hyperactivity disorder (ADHD) heavy hitter Vyvanse, the company's portfolio of newer products continues to hold the sales line. During the first nine months of Takeda's 2023 fiscal year, the drugmaker's growth and launch products grew sales 12.7% at constant currencies, Takeda said in a Thursday earnings presentation (PDF). The portfolio accounted for 43% of Takeda’s total sales haul for the period, which ended Dec. 31. Overall, Takeda's global revenues for the nine-month period came to 3.21 trillion Japanese yen (about $22 billion). The number was flat from the prior year at constant exchange rates, but Takeda appears to be taking that performance in stride considering the fact that it’s facing “significant” pressure from Vyvanse generics in the U.S. On that front, Vyvanse sales fell 12.1% to 312.9 billion yen ($2.14 billion), a performance that was “as expected” following the blockbuster’s loss of exclusivity in August. Takeda reports that nine generics to the drug have launched since Aug. 24. Vyvanse's market-share erosion in the U.S. was “slightly milder than initially anticipated,” Takeda said, thanks to constraints on generic supplies of the med. But the generic supply constraints should ease in the coming months, according to Takeda. Meanwhile, Takeda has recently added a pair of new drugs to its launch roster: Fruzaqla, approved in previously treated metastatic colorectal cancer, and Adzynma, an enzyme replacement therapy for congenital thrombotic thrombocytopenic purpura. The stars of Takeda’s drug debut catalogue, however, are its Entyvio pen for inflammatory bowel disease (IBD) and its dengue fever vaccine Qdenga. In recent months, Entyvio maintained its top position in the U.S. IBD market, Takeda said, growing global sales 7% during the first nine months of the company's fiscal year. Entyvio launched in pen form for ulcerative colitis in the U.S. in November. Since then, the drug-device combo has witnessed a “high level of interest and growing formulary access,” Takeda pointed out. Early this year, Takeda hopes to secure a nod for Entyvio in Crohn’s disease. Moving over to Qdenga, the dengue vaccine has now launched in Indonesia, Brazil, Thailand and Argentina. Plus, the shot has experienced “strong initial demand” in private markets, Takeda said. Qdenga has made its way onto some formal government immunization programs, including in Brazil. Elsewhere, Takeda says it’s engaged in “productive discussions” with governments in endemic regions to get the vaccine added to national immunization programs. In the aftermath of Vyvanse’s loss of exclusivity, Takeda is making bold pledges to investors to get its business back on track. In the near term, meaning fiscal year 2024 through 2025, Takeda aims to return to sales, profit and margin growth, the company said in its earnings presentation. Over the medium term, which runs into the early 2030s, Takeda plans to continue expanding the reach of its new medicines. In addition, Takeda hopes to secure more launches from its late-stage pipeline and enjoy “limited” generic competition before the advent of Entyvio biosimilars.

Takeda Pharmaceutical is stocking up its rare disease drug pipeline, reaching a deal for global rights to a Protagonist Therapeutics drug in late-stage development for the treatment of the rare blood disorder polycythemia vera. Under deal terms announced Thursday, Takeda is paying $300 million up front to share in the development of the drug, rusfertide. Newark, California-based Protagonist remains responsible for completing the ongoing Phase 3 test and submitting the drug for FDA review. If it’s approved, Takeda will lead commercialization of the drug. Polycythemia vera is an overproduction of blood cells. It’s caused by a mutation in the stem cells of the bone marrow, where red blood cells are produced. In addition to the higher red blood cell count, patients experience iron deficiency. The disorder raises the risk of cardiovascular events, such as heart attack and stroke. One common treatment for polycythemia vera is phlebotomy, frequent withdrawals of blood that decreases blood volume and reduces the levels of excess blood cells. Rusfertide is a peptide from Protagonist’s peptide technology platform. The company said the drug’s exact mechanism of action is not known, but it’s thought to regulate iron homeostasis and control the absorption, storage, and distribution of iron in the body. In an open-label Phase 2 clinical trial enrolling 70 participants, Protagonist reported that the once-weekly injectable drug controlled red blood cell levels and eliminated the need for phlebotomies, achieving the main study goal. Longer-term data presented in December during the annual meeting of the American Society of Hematology showed the drug continued to show durable effects through two-and-a-half years. A 250-patient, placebo-controlled Phase 3 study is underway with the same main goal as the mid-stage test. Protagonist expects to complete enrollment in the current quarter. In this 32-week study, rusfertide or a placebo will be added to a patient’s current polycythemia vera therapy. In an investor presentation, Protagonist said it expects to have 32-week data in the first quarter of next year, potentially setting the stage for an FDA submission in the fourth quarter of 2025. If rusfertide reaches the market, the deal calls for Takeda and Protagonist to split profits equally. Protagonist has an option to share in the marketing of the drug in the U.S. The biotech also has the right to opt-out of the profit share provision of the deal. Doing so would put Protagonist in line for opt-out payments and enhanced milestone and royalty payments. If Protagonist exercises either option, Takeda will still retain full rights to rusfertide outside of the U.S. According to a Protagonist regulatory filing, exercising the full opt-out right would put the company in line for up to $975 million in payments. For Takeda, rusfertide fits with the pharma giant’s strategy of acquiring late-stage assets in rare diseases, Julie Kim, president, U.S. business unit and U.S. country head, Takeda, said in a prepared statement. It also fits with other assets in the pharma giant’s hematology portfolio. This past November, the FDA approved Takeda’s Adzynma, a treatment for congenital thrombotic thrombocytopenic purpura, a rare inherited enzyme deficiency that leads to blood clotting problems. Protagonist does not yet have any FDA-approved products. President and CEO Dinesh Patel said the Takeda deal allows his company to focus on completing rusfertide’s Phase 3 study while leveraging Takeda’s global commercialization capabilities to immediately start pre-commercial work. “As we progress towards a fully integrated pharmaceutical company, this deal mitigates the inherent execution risks of a first-time commercial launch, optimizes the timing and enhances the scope for peak potential sales of rusfertide, while still allowing us to actively participate in the commercial experience and economics with a 50:50 profit split in the U.S. market,” Patel said. PharmaEssentia claimed the first FDA approval of a polycythemia vera therapy in 2021. This injectable drug, named Besremi, is an engineered version of interferon alpha. It’s believed to activate a signaling cascade that reduces production of red blood cells. Others developing potential treatments for the disease include Silence Therapeutics with a drug that employs RNA interference, and Ionis Pharmaceuticals, whose drug candidate is an antisense oligonucleotide.