A Takeda Pharmaceutical drug in growth for uncommon types of epilepsy which are immune to anti-seizure medicines has failed to satisfy the primary objectives of two placebo-controlled pivotal research, a setback to a program the Japanese pharmaceutical big had in-licensed to bolster its neuroscience pipeline.
Takeda didn’t disclose full particulars in its Monday announcement concerning the drug, soticlestat. Within the Section 3 check in sufferers with Dravet syndrome, the corporate stated the drug “narrowly missed” the primary aim of lowering convulsive seizures. Nevertheless, Takeda additionally pointed to encouraging outcomes on the trial’s six secondary measures. In a separate Section 3 check in Lennox-Gastaut syndrome, Takeda stated the drug missed the first endpoint, a measure of discount in seizure frequency.
In each medical trials, Takeda stated some pre-specified affected person subgroups confirmed nominally vital remedy results on the first and secondary efficacy endpoints of caregiver and clinician world impression of enchancment. The corporate additionally famous enchancment in seizure depth and period over the 16-week remedy interval. Takeda is continuous to investigate the soticlestat knowledge. It added that the twice-daily tablet was effectively tolerated by sufferers, exhibiting a security profile according to earlier exams of the drug.
Soticlestat is small molecule designed to dam ldl cholesterol 24-hydroxylase (CH24H), an enzyme discovered primarily within the mind. Elevated ranges of this enzyme are related to activation of receptors that play a job in epilepsy. The drug originated in Takeda’s labs and was outlicensed to Ovid Therapeutics in 2017. Per the deal phrases, the 2 corporations shared within the growth of the drug. In Ovid’s fingers, soticlestat met the primary aim of lowering seizure frequency in a Section 2 examine enrolling each Dravet and Lennox-Gastaut sufferers.
In 2021, Takeda paid Ovid $196 million up entrance to regain full rights to soticlestat, which on the time was prepared for Section 3 exams in Dravet and Lennox-Gastaut. The deal put Ovid in line for as much as $660 million in milestone funds relying on the drug’s progress below Takeda, plus royalties from gross sales if an permitted product reaches the market.
FDA-approved therapies for Dravet embody Jazz Prescribed drugs’ Epidiolex, a drug derived from hashish, and Fintepla, a UCB drug. The medication used to deal with Lennox-Gastaut are older antiepileptic medicines. Sarah Sheikh, head, neuroscience therapeutic space unit and head, world growth at Takeda, acknowledged soticlestat’s disappointing outcomes on the primary Section 3 objectives, however added that sufferers who’ve uncommon types of epilepsy are usually not well-served by presently accessible therapies. Medication for each Dravet and Lennox-Gastaut don’t adequately management seizures and have tolerability points, she stated in a ready assertion.
“Whereas we might have wished for extra declarative outcomes on the first endpoints, we’re inspired by constructive outcomes seen within the totality of the info and are trying ahead to participating well being authorities to find out the perfect path ahead,” Sheikh stated.
The totality of knowledge will possible transcend the encouraging secondary endpoints of the Dravet Section 3 examine and embody the constructive Section 2 outcomes. Takeda stated a pooled evaluation of the Section 2 cohort in Dravet and the Section 3 knowledge in that indication confirmed a discount from baseline in convulsive seizure frequency in comparison with placebo. These outcomes are persuasive to William Blair analyst Tim Lugo. In a be aware despatched to traders on Monday, Lugo wrote that the general knowledge are supportive of the drug’s exercise in Dravet syndrome, a type of epilepsy through which about 85% of sufferers expertise seizures that aren’t attentive to accessible medicines. In lots of instances, sufferers can take as much as three anti-seizure medication on the similar time. Lugo doesn’t see a future for the drug in Lennox-Gastaut, however he added {that a} path ahead in Dravet would depend on regulatory flexibility and a dedication from Takeda.
“Whereas we consider the info are clearly suggestive of soticlestat exercise in [Dravet syndrome], with blended knowledge, we’re much less sure {that a} multinational pharmaceutical firm similar to Takeda will likely be aggressive on the regulatory entrance and see incremental threat for the asset in Takeda’s fingers,” Lugo stated.
As for Ovid, the cash from promoting soticlestat’s rights has been put to work constructing extra diversified drug pipeline. Final 12 months, the corporate licensed rights to a Graviton Biosciences ROCK2 inhibitor now referred to as OV888, which is in early-stage medical growth for treating cerebral cavernous malformations. The deal additionally provides Ovid rights to Graviton’s library of ROCK2 inhibitors for different uncommon central nervous system issues. This program is on monitor to submit Section 1 knowledge quickly, paving the best way for the beginning of a Section 2 medical trial later this 12 months anticipated to provide knowledge within the first half of 2026. One other program, OV239, is predicted to report Section 1 knowledge within the second half of this 12 months. Licensed from Northwestern College, this drug is a GABA-aminotransferase inhibitor in growth for refractory seizures.
A 2022 cope with AstraZeneca introduced Ovid preclinical small molecules with potential functions that embody epilepsy. Essentially the most superior of them is an activator for potassium chloride co-transporter 2 (KCC2), a goal within the mind related to many neurological and psychiatric issues. Ovid plans to submit an investigational new drug utility for this drug candidate, OV350, in a yet-to-be disclosed psychiatric indication within the second half of this 12 months. Ovid stated Monday that it tasks its money reserves will assist the corporate into the primary half of 2026, when its most superior applications are anticipated to have medical updates.
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