Adjunctive achievement

NEW HAVEN, Conn.—Obsessive-compulsive disorder (OCD), a serious psychiatric condition affecting more than 2 million individuals in the U.S., significantly impacts quality of life. OCD is often a long-lasting disorder in which people have uncontrollable, reoccurring thoughts (obsessions) and behaviors (compulsions) that they feel compelled to repeat over and over.

About 40 to 60 percent of OCD patients continue to experience significant residual symptoms despite approved therapies. Some refractory patients undergo psychosurgery—such as cingulotomy or deep brain stimulation—to alleviate their symptoms.

Biohaven Pharmaceutical Holding Co. Ltd., a biopharmaceutical company focused on developing and commercializing therapies for debilitating neurological and neuropsychiatric diseases, reported top-line results from its proof-of-concept study of troriluzole in the treatment of OCD. Troriluzole 200 mg, administered once daily as adjunctive therapy in OCD patients with inadequate response to standard-of-care treatment, showed consistent numerical improvement over placebo on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) at all study timepoints (weeks four to 12), but did not meet the primary outcome measure at week 12.

Troriluzole was well tolerated, with a safety profile consistent with past clinical trial experience. Given the strong signal in this proof-of-concept study, Biohaven plans to advance troriluzole to a full Phase 3 development program in OCD, with a larger sample size and the addition of a higher-dose arm. There will be two Phase 3 clinical trials to generate the data needed for FDA approval, according to Dr. Vlad Coric, CEO of Biohaven.

Troriluzole is a third-generation prodrug and new chemical entity that modulates glutamate, the most abundant excitatory neurotransmitter in the human body. The primary mode of action of troriluzole is normalization of synaptic levels of glutamate. Troriluzole increases glutamate uptake from the peri-synaptic space by augmenting the expression and function of excitatory amino acid transporters located on glial cells that play a key role in clearing glutamate from the synapse.

According to Coric, “We advanced troriluzole in a series of proof-of-concept trials to assess signal detection across disease states. Our strategy is to only further invest in troriluzole indications where we find an emerging drug signal. We are pleased to report these OCD study results that show a consistent and clinically meaningful drug effect at all study timepoints in patients who had an inadequate response to existing standard-of-care treatments. This study provides our R&D team with the necessary data to refine and adequately power subsequent trials to advance troriluzole in OCD. Based upon these results, we will have an end of Phase 2 meeting with the FDA and plan to initiate an appropriately powered pivotal Phase 3 study of two doses of troriluzole versus placebo."

“Most treatments for OCD target the brain neurotransmitter serotonin, but a large number of patients treated with SSRIs do not fully respond to treatment,” he added. “Multiple lines of evidence suggest that the brain neurotransmitter glutamate plays an important role in OCD symptoms. Troriluzole normalizes brain glutamate levels, and it is hypothesized that normalizing glutamate levels may be therapeutic in OCD.”

Coric explained that he ran the Yale OCD Research Clinic prior to his career in drug development, and his academic research at Yale focused on the use of glutamate modulating drugs in OCD and other neuropsychiatric disorders. “Glutamate is the most abundant excitatory neurotransmitter in the brain; when levels are high, it could cause or worsen a number of neuropsychiatric disorders,” he noted.

Dr. Christopher Pittenger—who is associate professor of psychiatry, director of the Yale OCD Research Clinic and an investigator in the trial—commented, "OCD affects one person in 40 and can be debilitating. Fully a third of patients do not respond to current treatments, and many who do respond continue to suffer from residual symptoms. New therapies are urgently needed to alleviate this suffering and disability. There has not been a mechanistically novel medication approved for OCD in over 20 years. If troriluzole proves to be effective for these patients, it would be a huge advance. I look forward to working with Biohaven to explore the data from this proof-of-concept trial in more depth to inform the design of future pivotal studies."