Soticlestat

Ovid’s deal with Takeda included up to $660 million in milestones. Takeda’s late-phase epilepsy program has failed a key test, chalking up misses on the primary endpoints in pivotal trials in two indications. But the Japanese drugmaker still plans to talk to regulators about the next steps for the Ovid Therapeutics-partnered prospect based on the “totality of the data.” The drug candidate, the cholesterol 24 hydroxylase inhibitor soticlestat, is central to Takeda’s plans. With the company’s neuroscience unit currently lacking a launch product, and few other phase 3 readouts imminent, soticlestat represents a chance to get sales moving in the right direction. Bringing the drug to market would allow Takeda to start recouping the $196 million it paid Ovid in 2021. Yet, the phase 3 readouts fell short of the hoped-for slam dunk. A phase 3 trial in patients with refractory Lennox-Gastaut syndrome, a severe form of epilepsy, missed its primary endpoint. The endpoint looked at the change in Major Motor Drop seizure frequency from baseline as compared to placebo.     A phase 3 trial in refractory Dravet syndrome, another form of epilepsy, also missed its primary endpoint but Takeda identified more silver linings in its analysis of that dataset. The Dravet study narrowly missed its primary endpoint of reduction from baseline in convulsive seizure frequency as compared to placebo, achieving a p value of 0.06, and met secondary objectives. Takeda reported significant changes in the responder rate, measures of caregiver and clinician global impression of improvement, and seizure intensity and duration scales over the 16 weeks of treatment. Sarah Sheikh head of the neuroscience therapeutic area unit at Takeda, discussed the unmet needs in the two indications and the next steps for soticlestat in a statement. “While we would have wished for more declarative results on the primary endpoints, we are encouraged by positive outcomes seen in the totality of the data and are looking forward to engaging health authorities to determine the best path forward,” Sheikh said. Ovid published its own statement about the results, in which it explained how the upfront payment it received from Takeda supported development of a pipeline led by two clinical candidates. The biotech said it “will prioritize and pursue its programs with financial discipline” and expects its cash runway to last into the first half of 2026. Ovid is aiming to pass several clinical milestones before its cash runs dry. Investors were unmoved by the positive take on Ovid’s position, sending shares in the biotech down more than 60% to $1.20 in premarket trading. Ovid’s deal with Takeda included up to $660 million in milestones tied to the successful development, authorization and commercialization of soticlestat.

Two late-stage studies of Takeda’s experimental drug soticlestan in patients with Dravet syndrome and Lennox-Gastaut syndrome failed to meet their primary endpoints, although the company pointed out that one of the trials only “narrowly” missed, offering a glimmer of hope for the selective CH24H inhibitor.“While we would have wished for more declarative results on the primary endpoints, we are encouraged by positive outcomes seen in the totality of the data and are looking forward to engaging health authorities to determine the best path forward,” remarked Sarah Sheikh, head of global development at Takeda.The SKYLINE study included 144 paediatric and young adult participants with refractory Dravet syndrome, while the SKYWAY trial enrolled 270 paediatric and adult patients with Lennox-Gastaut syndrome. In both studies, participants were randomised to receive soticlestat or placebo twice daily for 16 weeks on top of their current antiseizure therapy. SKYLINE’s primary endpoint was percent change from baseline in convulsive seizure frequency per 28 days, while the main goal of SKYWAY was percent change from baseline in major motor drop (MMD) seizure frequency per 28 days.Top-line results showed that soticlestat narrowly missed the primary endpoint in SKYLINE, with a p-value of 0.06. Takeda added that in the study, the drug showed clinically meaningful and nominally significant results in a number of key secondary goals, including responder rate, and seizure intensity and duration scales. The company did not provide details of how soticlestat fared on secondary endpoints in the SKYWAY trial.Takeda indicated that the drug, also known as TAK-935, was generally well tolerated in both studies. The drugmaker said it will assess the financial impacts of the results, including any impairment loss for intangible assets, having paid nearly $200 million back in 2021 to regain full rights to soticlestat from Ovid Therapeutics.