CH24H

Takeda previously noted the “totality of the data” to make the case soticlestat had a future in Dravet. \n Takeda has axed plans to seek approval for its failed epilepsy drug candidate soticlestat. The Japanese drugmaker pulled the plug on the program after the FDA pointed out the shortcomings of its clinical data package.Soticlestat, a cholesterol 24 hydroxylase inhibitor, failed phase 3 trials in two forms of epilepsy last year. The studies showed the molecule was statistically no better than placebo at reducing the frequency of seizures in people with Lennox-Gastaut syndrome (LGS) and Dravet syndrome. Takeda soon removed the LGS program from its pipeline and reported a $140 million charge related to the molecule.Yet, Takeda noted the “totality of the data”—a favorite phrase of sponsors of failed trials—to make the case soticlestat had a future in Dravet. The FDA quashed Takeda’s hopes. According to Takeda, the U.S. regulator said the current data is incapable of showing substantial evidence of effectiveness in Dravet.Takeda uploaded the phase 3 data to ClinicalTrials.gov late last year. The update shows Dravet patients on soticlestat experienced a 22.16% reduction in convulsive seizure frequency per 28 days, compared to an 8.64% reduction in the placebo group. The difference fell short of statistical significance, yielding a p-value of 0.061. Takeda linked the drug candidate to nominally significant changes on six secondary endpoints, tracking positive shifts in responder rate, measures of caregiver and clinician global impression of improvement, and seizure intensity and duration scales over the 16-week treatment period. Coupled with the relatively narrow miss on the primary endpoint, Takeda thought the secondary measures could get it over the line.The company’s inability to convince the FDA of the strength of the data package has implications for Ovid Therapeutics and Ligand Pharmaceuticals. Ovid inked a deal with Takeda in 2021 and sold part of its royalty rights to Ligand in 2023. The failure of the phase 3 soticlestat trials sparked changes at Ovid, which would have been in line for milestones and royalties if the molecule had come to market. The removal of soticlestat wasn\'t the only change that Takeda revealed today. The company also announced that Julie Kim, president of Takeda’s U.S. Business Unit, will take over from CEO Christophe Weber when Weber retires in June 2026.

The oral version of OV329—a GABA-aminotransferase inhibitor for the chronic treatment of epilepsies—will remain one of Ovid Therapeutics' top priorities. Ovid Therapeutics already revealed last month that it was trimming back its headcount as the company navigates an unexpected setback for the Takeda-partnered epilepsy med soticlestat. Now, the biotech has confirmed that it’s halting work on its preclinical programs, including an intravenous (IV) formulation of its seizure drug in order to save cash.The company already made clear in a regulatory filing at the time that laying off 17 people—equivalent to 43% of Ovid’s workforce—in July was spurred by a need to “prioritize its programs and extend its cash runway.”In its second-quarter earnings report this morning, the biotech spelt out what pipeline changes it had in mind. The company is halting its preclinical work—although the only high-profile casualty will be the IV formulation of OV329.While Ovid also referred to “other preclinical programs” as facing the axe, it didn’t go into further details.Instead, the oral version of OV329—a GABA-aminotransferase inhibitor for the chronic treatment of epilepsies—will remain one of the company’s top priorities. A phase 1 multiple ascending dose study is expected to wrap up this year. The other key priority for Ovid is OV888/GV101, a Graviton Bioscience-partnered ROCK2 inhibitor capsule that is being lined up for a phase 2 study in cerebral cavernous malformations. With $77 million to hand in cash and equivalents, the company expects to pave a cash runway into 2026.Ovid CEO Jeremy Levin put the pipeline changes in the context of the failure of soticlestat to reduce seizure frequency in patients with refractory Lennox-Gastaut syndrome, a severe form of epilepsy, in a phase 3 trial in June. Ovid sold its rights to the cholesterol 24 hydroxylase inhibitor to Takeda for $196 million back in 2021 but is still in line for commercial milestones and low double-digit royalties up to 20% on global net sales.“Following Takeda's unexpected phase 3 results for soticlestat, we moved rapidly to focus our resources to preserve capital,” Levin said in today’s release. “This approach included restructuring the organization and initiating ongoing program prioritization efforts to support the achievement of meaningful clinical and regulatory milestones within our financial plan.”Takeda was also taken aback by soticlestat’s failure. The Japanese pharma notched a $140 million impairment charge as a result of the phase 3 miss. Still, Takeda said recently that it still holds some hope that the “totality of the data” could one day earn an FDA nod anyway. 

In its quarterly results presentation Wednesday, Takeda disclosed a JPY 21.5 billion ($143 million) impairment charge on its rare epilepsy drug soticlestat. The company shelled out nearly $200 million upfront back in 2021 to regain full rights to the CH24H enzyme inhibitor from Ovid Therapeutics.The financial hit comes in the wake of disappointing Phase III results reported a few weeks ago. The pivotal SKYLINE and SKYWAY trials targeting Dravet syndrome and Lennox-Gastaut syndrome (LGS), respectively, failed to meet their primary endpoints. Although the LGS programme has been dropped, Takeda said SKYLINE only "narrowly" fell short of its objective and it remains cautiously optimistic about soticlestat's potential in the Dravet indication.The company said the "totality" of data for Dravet syndrome patients "suggests clinically meaningful benefit" despite the primary endpoint miss.In other pipeline updates, the company said it has also ended its Phase III programme for pabinafusp alfa (TAK-141/ JR141) in Hunter syndrome for EU markets, following a strategic review of its alliance with JCR Pharmaceuticals. JCR remains the drug's study sponsor and plans to continue the Phase III trial for participating patients.In addition, an early-stage trial for ponatinib in paediatric Philadelphia chromosome-positive acute lymphoblastic leukaemia was "closed due to dose-limiting toxicities."Meanwhile, Takeda reported a "strong" overall performance for the first fiscal quarter. Revenue grew by 14.1% to JPY 1.2 trillion ($8 billion), driven by its growth and launch products portfolio, which saw a 17.8% gain at constant currencies. The segment now represents nearly half of total revenue, according to the company.Its ulcerative colitis and Crohn's disease treatment Entyvio saw sales surge by 22.1% to JPY 234.4 billion. The company's rare diseases portfolio grew by 16.8% to JPY 199.5 billion, buoyed by Takhzyro's 35.6% growth to JPY 56 billion. Plasma-derived therapies climbed by 29.7% to JPY 271.4 billion.Milano Furuta, the company's chief financial officer, maintained a cautious outlook for the remainder of the fiscal year, which is unchanged from May, saying "we expect the impact of generic erosion to accelerate in coming quarters and the phasing of our R&D investment will focus on the second half of the year due to the planned initiation of multiple Phase III programmes."The Japanese pharma unveiled a $900-million restructuring plan earlier this year that will affect 641 employees at two sites in the Boston area.