Darvadstrocel ( TiGenix)

Pictured: Takeda's office in Cambridge, Massachusetts/iStock, hapabapa Takeda on Thursday released the business report for its 2023 fiscal year, touting a modest increase in annual revenue while forecasting a profit hit for the coming year tied to the continued sales erosion of its ADHD therapy Vyvanse (lisdexamfetamine dimesylate). For the fiscal year that ended March 31, 2024, Takeda booked more than $27 billion in revenue. This figure represents a 1.5% increase at constant exchange rates from its fiscal year 2023 revenue of $25.8 billion. Despite the revenue bump, Takeda’s net profit for the year dropped 57% to $925 million, from approximately $2 billion during the previous fiscal year. Takeda’s reported operating profit likewise took a 50.3% hit, dropping from $3.15 billion to $1.37 billion in the fiscal year 2023. According to the pharma’s investor presentation, the drop in reported operating profit could be attributed to higher operating expenditure as well as “impairments” with its Crohn’s disease stem cell therapy Alofisel (darvadstrocel) and lung cancer tyrosine kinase inhibitor Exkivity (mobocertinib). In October 2023, Alofisel failed its Phase III ADMIRE-CD II study, unable to significantly improve 24-week combined remission in patients with complex Crohn’s perianal fistulas. The company subsequently decided not to regulatory approval in the U.S., according to its presentation on Thursday. The same month, Takeda withdrew Exkivitiy globally after it failed the confirmatory Phase III EXCLAIM-2 study. Looking ahead to the rest of the current fiscal year, Takeda tempered investor expectations and lowered its core operating profit guidance by approximately 10%. The Japanese multinational now anticipates booking around $6.4 million (or ¥1 billion) in the coming year. Takeda’s forecast also includes a “flat to slightly declining” annual revenue. This annual guidance reflects the continued sales erosion that Takeda is expecting to weather as generic versions of its ADHD medicine Vyvanse hit the market. First approved in 2003, Vyvanse lost several crucial patent protections in 2023, including those that covered adult indications in February, and those for pediatric use in August. There are at least 12 impending generic version of Vyvanse from companies such as Sandoz, Teva and Mylan. Takeda has lined up several upcoming pipeline milestones to make up for Vyvanse’s loss of exclusivity. In the coming fiscal year, for instance, it is planning to launch a Phase III study of its tyrosine kinase 2 inhibitor zasocitinib in psoriatic arthritis, as well as a head-to-head study versus BMS’s Sotyktu (deucravacitinib) in psoriasis. The pharma is also awaiting a Phase III readout for its cholesterol 24-hydroxylase inhibitor soticlestat in the first half of the fiscal year. The drug candidate is being studied for Dravet syndrome or Lennox-Gastaut syndrome, two rare epileptic conditions. Aside from its promising pipeline, Takeda will also implement an “enterprise-wide efficiency program,” which will start in fiscal year 2024, according to its business report. The pharma expects this strategic initiative to cost nearly $900 million. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

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.