Findings Demonstrate Promising Anticonvulsant Activity with CVL-865,
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 CVL-865 in Broader Epilepsy
Populations
BOSTON–(BUSINESS WIRE)–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 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). This model is commonly used to establish
proof-of-principle in antiepileptic drug development.
“We are encouraged by the robust anticonvulsant activity of CVL-865
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 CVL-865 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 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 (PPR). -
Seven study participants with a PPR to intermittent photic stimulation
(IPS) 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. -
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 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 percent) who received either dose
of CVL-865 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 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.
About CVL-865
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.
About Cerevel Therapeutics
Cerevel Therapeutics (www.cerevel.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.
ENDNOTES:
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.
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W2O pure
reides@purecommunications.com