Therapy Areas: Central Nervous System
Results from Cerevel Therapeutics Phase 2a Study Results Published in Neurology on Its Most Advanced Investigational Epilepsy Treatment
10 April 2019 - - Results from US-based biopharmaceutical company Cerevel Therapeutics' Phase 2a study have been published in Neurology demonstrating the anticonvulsant activity of CVL-865 (formerly PF-06372865), a novel α2/3/5-subtype selective GABAA positive allosteric modulator, in patients with photosensitive epilepsy (seizures triggered by visual stimuli), the company said.

This model is commonly used to establish proof-of-principle in antiepileptic drug development.

According to the Epilepsy Foundation, epilepsy is the fourth most common neurological disorder and affects people of all ages.

Epilepsy is a spectrum condition with a range of seizure types and control varying from person-to-person.

It is estimated that one-third of people with epilepsy have seizures that are refractory (resistant) to treatment and continue to experience uncontrolled breakthrough episodes that negatively impacts quality of life, increases the risk of sudden unexplained death, and places a substantial burden on patients and caregivers.

As such, antiepileptic therapies that employ new mechanisms are desperately needed.

This multicenter, double-blind, single-dose, randomised, placebo- and active-controlled, four-period cross-over Phase 2a study used a clinical model of epilepsy to establish proof-of-principle of efficacy of CVL-865.

The epilepsy photosensitivity model includes study participants who have reproducible generalized epileptiform discharges on electroencephalogram stimulated by flashing lights within a range of frequencies called a photoparoxysmal response.

Seven study participants with a PPR to intermittent photic stimulation at baseline were randomized to single doses of CVL-865 (17.5 or 52.5 mg), lorazepam 2 mg (a commonly prescribed benzodiazepine used as an active control), or placebo.

Standardised photosensitivity ranges to IPS were performed at zero, one-, two-, four-, and six-hours post-dose.

The primary endpoint was the average least squares mean change in the SPR in the participant's most sensitive eye condition, across all time points.
Phase 2a Study Key Findings:

Both the 17.5 mg and 52.5 mg single doses of CVL-865 and 2 mg lorazepam produced a marked and statistically significant mean reduction in SPR compared to placebo.

Six of seven study participants (86%) who received either dose of CVL-865 or lorazepam 2 mg had complete suppression of IPS whereas five of seven participants (71%) who received placebo had no response.

The tolerability of CVL-865 was comparable to that observed in previous studies of the compound. The most common side effects were dizziness and somnolence (drowsiness). No serious adverse events were reported.

CVL-865 is a novel α2/3/5-subtype selective GABAA positive allosteric modulator. It has been structurally differentiated from classical benzodiazepines to minimize activity at α1-containing receptors which is believed to help mediate many of the adverse events associated with this class of medicines.

Cerevel Therapeutics is a biopharmaceutical company focused on developing new medicines to treat disorders of the central nervous system.

The company has a diversified neuroscience pipeline comprising three clinical-stage investigational therapies and several pre-clinical compounds with the potential to treat a broad range of neurological and neuropsychiatric disorders, including epilepsy, Parkinson's, Alzheimer's, schizophrenia and addiction.

Headquartered in the Greater Boston area, Cerevel was formed in 2018 through a partnership between Bain Capital and Pfizer.