RARE Daily

Ovid Reports Results from Studies in Rare Epilepsies

October 1, 2020

Rare Daily Staff

Ovid Therapeutics reported mixed results from its phase 2 study and open label extension study that showed its experimental therapy soticlestat reduced seizures in patients with rare epilepsies.

The studies looked at patients with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) and Duplication 15q (Dup15q) syndrome. Both conditions are rare and severe developmental and epileptic encephalopathies (DEEs) caused by genetic mutations. These mutations are thought (among other effects) to result in excess transmission of glutamate, an excitatory neurotransmitter, that in turn leads to epilepsy and other characteristic neurobehavioral symptoms of CDD and Dup15q syndrome. Despite the availability of medicines for epilepsy generally, there are no approved therapies for CDD and Dup15q syndrome.

Soticlestat, which Ovid is developing in collaboration with Takeda Pharmaceutical, is a potent, highly selective, first-in-class inhibitor of the enzyme cholesterol 24-hydroxylase (CH24H), with the potential to reduce seizure susceptibility and improve seizure control. CH24H is predominantly expressed in the brain, where it converts cholesterol into 24S-hydroxycholesterol (24HC) to adjust the homeostatic balance of brain cholesterol. 24HC is a positive allosteric modulator of the NMDA receptor and modulates glutamatergic signaling associated with epilepsy. Glutamate is one of the main neurotransmitters in the brain and has been shown to play a role in the initiation and spread of seizure activity.

Together, data from the ARCADE and ENDYMION studies show seizure frequency reduction over time. In 12 CDD patients, median motor seizure frequency reduction was 24 percent during the 12-week maintenance period in the ARCADE study, increasing to a 50 percent reduction in the ENDYMION long-term extension study in the five CDD patients who reached nine months of continuous treatment.

However, in the eight Dup15q patients in the studies, there was an increase in median motor seizure frequency in the ARCADE study during the 12-week maintenance period. Longer-term data from the four Dup15q patients who reached nine months of continuous treatment showed a 74 percent reduction in median motor seizure frequency.

Soticlestat was generally well tolerated in both studies and continues to demonstrate a favorable safety profile. Data reported today are consistent with, and build upon, previous findings with soticlestat.

“CDD and Dup15q patients have various seizure types and are on multiple concomitant antiseizure medications per current medical practice, and yet they still lack significant control of their respective seizures,” said Amit Rakhit, president and chief medical officer of Ovid Therapeutics. “Data from ARCADE, while a small open-label study, and ENDYMION support previous findings of the early activity of soticlestat, and importantly, the longer-term ENDYMION study shows seizure frequency reduction across multiple rare epilepsies over time.”

Photo: Amit Rakhit, president and chief medical officer, Ovid Therapeutics


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