Takeda and Ovid’s epilepsy drug topped placebo at reducing seizure frequency in children with rare, genetic forms of epilepsy, topline phase 2 data show. The drug performed better in Dravet syndrome than in Lennox-Gastaut syndrome, teeing up a phase 3 study in the former, while prompting the partners to dig into the data for the latter to determine its next steps.
The phase 2 study pitted soticlestat, previously called OV935 or TAK-935, against placebo in 141 children aged 2 to 17 with hard-to-treat epilepsy syndromes, including Dravet and Lennox-Gastaut. After 20 weeks of treatment, Dravet patients taking soticlestat saw a median 34% reduction in convulsive seizures from baseline compared to placebo patients, who logged a 7% increase in seizures—a 46% difference.
In Lennox-Gastaut syndrome, patients taking soticlestat had a median 21% decrease in drop seizures—so called because a sudden loss of muscle strength can cause a person to drop to the floor—while placebo patients saw a 6% reduction in seizures, a difference of 15%. Though the drug beat placebo, the numbers did not hit statistical significance, so the companies continue to crunch the data to “better understand the potential next step” for soticlestat in this “highly heterogenous patient population,” they said in a statement.
All of the patients who finished the study continued into an open-label extension study that will look at the safety and tolerability of soticlestat over four years. It will also gauge the long-term effect of the drug on seizure frequency.
“It is exciting to see these positive results and to advance soticlestat into late stage clinical development—initially for the potential treatment of children with Dravet syndrome who need more options to manage treatment-resistant seizures,” said Sarah Sheikh, M.D., who leads Takeda’s neuroscience unit, in the statement. “Soticlestat and its novel mechanism of action were discovered at Takeda and we are enthusiastic about continuing to advance the science and clinical programs as one aligned team, in strong partnership with Ovid Therapeutics.”
Dravet and Lennox-Gastaut syndromes typically present in childhood, have a higher mortality rate than other types of epilepsy and are generally treatment-resistant. Takeda and Ovid teamed up in 2017 to develop soticlestat for these two syndromes. Unlike the usual pharma/biotech deal under which Takeda might buy into a promising drug from Ovid, it was Ovid that signed on to help the Japanese pharma develop the drug.
The next year, the duo added two more rare epilepsies to their partnership: CDKL5 deficiency disorder (CDD) and duplication 15q (Dup151) syndrome. They expect to report data from an open-label phase 2 study in those indications later this quarter, Ovid Chief Medical Officer Amit Rakhit, M.D., said in the statement.
Soticlestat inhibits an enzyme called CH24H that is expressed in the brain and plays a role in processing cholesterol. Research suggests that it is also involved in the over-activation of the glutamatergic pathway; the neurotransmitter glutamate is linked to the start and spread of seizure activity. The idea is that targeting CH24H could tamp down on glutamate activity and treat rare epilepsies.
There are a couple of drugs approved for Dravet syndrome, including GW Pharma’s cannabis-based Epidiolex, which earned the FDA nod in June 2018 for both Lennox-Gastaut and Dravet. But it couldn’t launch the drug in the U.S. until the Drug Enforcement Agency rescheduled cannabidiol, the active ingredient in Epidiolex, in April this year. Two months later, Zogenix’s Fintepla scored a nod for Dravet, and the company is pursuing an approval for Lennox-Gastaut, too.
As for approaches in development, Stoke Therapeutics raised $142 million in its IPO last year to bring its Dravet program from preclinical to phase 3. And Encoded Therapeutics is working on a gene therapy for Dravet that’s aimed at tackling gait problems, developmental delays and impaired coordination, as well as intractable seizures.