Vertex Pharmaceuticals Incorporated announced results from a recently completed phase 2 study of VX-765 in 60 people with treatment-resistant epilepsy. The primary endpoint of the study was safety and tolerability, and results from the study showed a similar safety profile for VX-765 as compared to placebo. Secondary endpoints and additional analyses evaluated the clinical activity of VX-765, and results support the initiation of a larger and longer-duration phase 2b study of VX-765 in people with treatment-resistant epilepsy. Vertex expects to begin this trial as early as the fourth quarter of 2011.

"The use of anti-inflammatory medicines is a completely new way to approach the treatment of epilepsy, and this study was an important first step toward understanding whether VX-765 could help people with this disease," said Peter Mueller, Ph.D., executive vice president, global research and development, and chief scientific officer for Vertex. "People who do not respond to standard medicines for epilepsy are often severely debilitated by frequent seizures that limit daily activities and independence. The results observed in this study provide support for the continued evaluation of VX-765 as part of a larger and longer-duration study in epilepsy planned for later this year."

The double-blind, randomized, placebo-controlled phase 2a study of VX-765 enrolled 60 people with treatment-resistant partial onset epilepsy, which is a type of epilepsy where the seizures start and occur in a specific part of the brain. The study enrolled and dosed people who did not benefit from the use of at least two currently available medicines for partial epilepsy. Patients received six weeks of treatment with VX-765 or placebo following a six-week baseline period to monitor seizure frequency. All patients in the study had at least six partial seizures during the baseline period. Patients were followed for six weeks after the treatment phase to collect additional safety and seizure information. Patients continued to receive standard medicines for epilepsy throughout the study, in addition to VX-765 or placebo. In the study, 48 people received 900 mg of VX-765 three-times-daily and 12 people received placebo three-times-daily.

The primary endpoint of the study was the safety and tolerability of VX-765. In the study, the safety profile for VX-765 was similar to that for placebo. The most common adverse events observed across both treatment arms were headache, dizziness, fatigue and gastrointestinal disorders, and the majority of these adverse events were mild to moderate. The only adverse event that was 10 percent or greater in frequency among those treated with VX-765 compared to placebo was dizziness. One person discontinued treatment due to adverse events during the study and was in the VX-765 treatment group.

Key secondary endpoints focused on the clinical activity of VX-765 during the study based on: (1) Percent reduction in seizure rate; (2) Percent of patients with a 50 percent or greater reduction in seizure frequency, known as the responder-rate; (3) Percent of patients who were seizure-free in the last two weeks of treatment.

In addition to the endpoints specified in the study protocol, a number of additional analyses were conducted to evaluate the clinical activity of VX-765 during the last two weeks of the treatment phase and first two weeks of the follow-up period. These evaluations included: (1) Percent of patients who were seizure-free during the first two weeks of the follow-up period only; (2) Percent reduction in seizure rate during the last two weeks of the treatment phase and first two weeks of the follow-up period only; (3) Percent of patients with a 50 percent or greater reduction in seizure frequency, known as the responder-rate, during the last two weeks of the treatment phase and first two weeks of the follow-up period only.

VX-765 is an oral medicine in development that is designed to inhibit Caspase-1, an enzyme involved in the production of IL-1 beta and linked to a wide range of immune and inflammatory responses. VX-765 has been shown to inhibit acute partial seizures in preclinical models and has shown activity in preclinical models of chronic partial epilepsy that do not respond to currently available medicines for epilepsy. Vertex holds worldwide rights to VX-765.

Epilepsy is a chronic neurological disorder characterized by recurrent seizures resulting from overactive neurons in the brain. Recent studies suggest that inflammation and overproduction of IL-1 beta may be associated with epileptic seizures. The Centers for Disease Control and Prevention (CDC) estimate that about 2 million people in the United States have epilepsy and nearly 140,000 Americans develop the condition each year. While there are a number of approved epilepsy medicines, more than 30 percent of people are not well-controlled on current treatments and continue to have seizures. Epilepsy can have a significant impact on people's quality of life and independence. The CDC estimates that the total indirect and direct cost of epilepsy in the United States is $15.5 billion.

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