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Cerevel Therapeutics Announces Publication of Phase 2a Study Results in Neurology on Its Most Advanced Investigational Epilepsy Treatment
Findings Demonstrate Promising Anticonvulsant Activity with darigabat, a Novel Selective GABA Potentiator, in Patients with Photosensitive Epilepsy
Company to Initiate Additional Phase 2 Study by Year-end to More Fully Characterize the Clinical Utility of darigabat in Broader Epilepsy Populations
BOSTON – April 9, 2019 – Cerevel Therapeutics, a biopharmaceutical company focused on developing new medicines to treat disorders of the central nervous system (CNS), today announced the publication of results from a Phase 2a study1 in Neurology demonstrating the anticonvulsant activity of darigabat (formerly PF-06372865), a novel α2/3/5-subtype selective GABAA positive allosteric modulator, in patients with photosensitive epilepsy (seizures triggered by visual stimuli). This model is commonly used to establish proof-of-principle in antiepileptic drug development.
“We are encouraged by the robust anticonvulsant activity of darigabat observed in this type of clinical study which has shown to be predictive of treatment success in broader epilepsy patient populations,” said Raymond Sanchez, M.D., chief medical officer of Cerevel Therapeutics. “We look forward to further evaluating the potential of darigabat to treat people living with epilepsy who do not respond to currently available therapies in a Phase 2 clinical trial that we plan to commence by year-end.”
According to the Epilepsy Foundation, epilepsy (often referred to as “seizure disorders”) is the fourth most common neurological disorder and affects people of all ages. Epilepsy is a spectrum condition with a wide 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 refractory2 (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.
Phase 2a Study Design:
- This multicenter, double-blind, single-dose, randomized, 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 darigabat.
- 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 (PPR).
- Seven study participants with a PPR to intermittent photic stimulation (IPS) at baseline were randomized to single doses of darigabat (17.5 or 52.5 mg), lorazepam 2 mg (a commonly prescribed benzodiazepine used as an active control), or placebo.
- Standardized photosensitivity ranges (SPRs) 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 darigabat and 2 mg lorazepam produced a marked and statistically significant mean reduction in SPR compared to placebo.
- Six of seven study participants (86 percent) who received either dose of darigabat or lorazepam 2 mg had complete suppression of IPS whereas five of seven participants (71 percent) who received placebo had no response.
- The tolerability of darigabat 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.
darigabat 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.
About Cerevel Therapeutics
Cerevel Therapeutics (cereveldev.wpengine.com) is a biopharmaceutical company focused on developing new medicines to treat disorders of the central nervous system (CNS). 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.
1 The Phase 2a study was conducted by Pfizer Inc. prior to Cerevel Therapeutics’ formation.
2 Kwan, P. and Brodie, M. J. Early identification of refractory epilepsy. N Eng J Med 2000; 342: 314-319.