Takeda Pharmaceuticals has acquired the global rights to develop and market the investigational oral therapy soticlestat (OV935/TAK-935) for developmental and epileptic encephalopathies, including Dravet syndrome, the company has announced.
Soticlestat was originally developed by Takeda and Ovid Therapeutics, after the companies entered into a collaboration in 2017.
Under the new agreement, Takeda is solely responsible for the worldwide development and commercialization of soticlestat, with Ovid having no financial obligations to Takeda under the original agreement.
Takeda now plans to start a Phase 3 trial of soticlestat for children and young adults with Dravet and Lennox-Gastaut Syndrome (LGS) in the second half of 2021.
“We are working diligently and expediently to initiate and execute upon the Phase 3 studies in children and young adults with [Dravet syndrome] and LGS,” said Sarah Sheikh, MD, head of neuroscience therapeutic area unit at Takeda. “Our goal is to one day bring new treatment options that provide greater seizure control, tolerability and function to [Dravet syndrome] and LGS patients around the world.”
Soticlestat is a potent, highly-selective, first-in-class suppressor of cholesterol 24-hydroxylase (CH24H), an enzyme that plays a major role in clearing brain cholesterol. The enzyme eventually causes the activation of NMDA receptors — found at most excitatory synapses, or nerve cell junctions — making nerve cells more prone to fire electrical signals.
By blocking CH24H and reducing NMDA receptor activation, soticlestat is thought to lower seizure susceptibility potentially in patients with developmental and epileptic encephalopathies.
The study assessed the therapy’s safety and effectiveness in 141 children and adolescents (ages 2 to 17) who experienced seizures associated with Dravet or LGS.
Participants were randomly assigned to soticlestat or a placebo for 20 weeks, which included eight weeks of dose optimization — ranging from 100 mg to 200 and 300 mg twice daily — followed by a 12-week period of maintenance treatment.
Patients were allowed to continue to receive up to four anti-seizure medications.
Top-line results from 139 patients (51 with Dravet syndrome and 88 with LGS) given at least one dose of soticlestat showed a median drop of 27.8% in their seizure rate vs a 3.1% median increase in participants given the placebo after 12 weeks — meeting the trial’s main goal of showing a significant drop in seizure rate.
This statistical significance was maintained during the 20-week treatment period, with soticlestat-treated patients showing a 25.1% placebo-adjusted reduction in seizure frequency. Also, the frequency of convulsive seizures dropped by a median of 33.8% in patients treated with soticlestat compared with a 7% median increase in those on a placebo.
In patients with LGS, although soticlestat also dropped seizure frequency, this change was not deemed statistically different compared to the placebo.
“I would like to thank Ovid for their thoughtful and productive collaboration,” said Andy Plump, MD, PhD, president of research and development at Takeda. “Together we generated positive Phase 2 ELEKTRA study data, and as a result, soticlestat is poised to enter two pivotal trials.”
Ovid will receive an upfront payment of $196 million and remains eligible for an additional $660 million upon meeting development, regulatory, and sales milestones.
Additionally, Ovid will collect tiered royalties and up to 20% of soticlestat sales, if the therapy is approved.
“This new agreement is a positive outcome for patients, for Ovid and for Takeda,” said Jeremy Levin, PhD, CEO of Ovid. “Jointly, we have set the stage, optimized the program and enabled it to accelerate.”
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