Rare Daily Staff

Ovid Therapeutics said results from a 12-week, phase 1b/2a clinical trial of OV935/TAK-935, its experimental therapy for rare developmental and epileptic encephalopathies (DEE), achieved its primary endpoint of safety and tolerability.

Epileptic encephalopathies include a group of epilepsy syndromes associated with severe cognitive and behavioral disturbances. These epilepsies cause significant morbidities for patients beyond what might be expected from the known underlying pathology alone and can worsen over time. Developmental and epileptic encephalopathies typically present early in life and often include treatment-resistant seizures throughout the person’s lifetime. Few treatment options are available.

OV935/TAK-935 is a potent, highly-selective, first-in-class inhibitor of the enzyme cholesterol 24-hydroxylase (CH24H) being investigated as an anti-epileptic drug. Recent literature indicates CH24H is involved in over-activation of a pathway involved in central nervous system diseases, such as epilepsy. In addition, preclinical data suggest OV935 modulates glial function and inflammation, which may impact disease pathology and the development of epilepsy. The company is collaborating with Takeda to develop the drug.

“There is an urgent need for new medicines to treat rare DEE,” said Jeremy Levin, chairman and chief executive officer of Ovid Therapeutics. “We believe further development of OV935 could provide an opportunity to address the needs of children and adults with these intractable epilepsies. Moreover, the anti-epileptogenic preclinical data, now coupled with the observed exploratory seizure data, suggest the potential of OV935 as an early treatment option.”

The primary objective of the phase 1b/2a clinical trial was to characterize the safety and tolerability profile of OV935 in adult patients with a documented DEE. The secondary objective was to characterize the multiple dose pharmacokinetics profile of OV935 in adults patients with a documented DEE.

Eighteen patients (aged 19 to 45 years) who had at least one motor seizure per month were enrolled. The majority of patients enrolled in the study were unsuccessfully treated with at least two prior treatment regimens and approximately 45 percent of patients were taking four or more anti-epileptic drugs.

OV935 achieved the primary endpoint of safety and tolerability as measured by incidence of adverse events. The data are consistent with a favorable safety and tolerability profile and support the continued clinical development of OV935. Adverse events that occurred more frequently in the OV935-treatment group versus the placebo group are: dysarthria, insomnia, lethargy, seizure cluster, and upper respiratory infection. Four patients discontinued due to an adverse event or a serious adverse event in the OV935 treatment arm.

An increase in seizure frequency was seen in three patients, all of whom were on the antiepileptic drug perampanel. This suggests the potential for a drug-drug interaction between medicines acting on different glutamatergic receptors. Accordingly, changes in seizure frequency data for the phase 1b/2a trial are reported today including and excluding the three patients on perampanel.

The company said the data reaffirm the pharmacodynamic profile seen in previous studies. Specifically, plasma levels of OV935 were dose-proportional and consistent with levels observed in four prior phase 1 studies in healthy volunteers.

Based on the results of the phase 1b/2a trial, Ovid and Takeda will continue with the dose and titration schedule used in their phase 2 ELEKTRA and ARCADE trials of OV935 in patients ages 2 to 17 years. In addition, Ovid will amend the protocols for these trials to exclude patients being treated with perampanel. The company will also extend the duration of treatment with the potential to observe the extent of the effects of OV935 on seizure reduction over time.

December 17, 2018
Photo: Jeremy Levin

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