Biohaven's Manic Monday: FDA Accepts Migraine Treatment NDA, SCA Trial Disappoints

Monday brought both a hit and a miss for New Haven, Connecticut-based Biohaven Pharma. Its new drug application (NDA) for its nasal spray to treat migraines was accepted by the U.S. Food and Drug Administration. This news was followed by a disappointing update that Biohaven’s Phase III trial of troriluzole, a drug for spinocerebellar ataxia, did not meet its endpoint.

If approved, Biohaven’s nasal spray, a drug called zavegepant, would be the only small molecule calcitonin gene-related peptide (CGRP) receptor antagonist in an intranasal formulation for the acute treatment of migraine. The FDA accepted the NDA on Monday. The Prescription Drug User Fee Act (PDUFA) goal date for completion of the FDA review is set for Q1 of 2023.

The NDA acceptance is based on Biohaven’s two pivotal double-blind, placebo-controlled studies that established the efficacy, tolerability and safety profile of zavegepant. Both studies showed that zavegepant was more effective than placebo at providing freedom from pain, as well as freedom from other symptoms such as nausea, sensitivity to light and sensitivity to sound.

Clinical studies showed that zavegepant can provide pain relief in as little as 15 minutes. The results lasted, too - sustained freedom from pain and sustained pain relief lasted for up to 48 hours.

"Many patients with migraine need treatments other than pills for at least some of their attacks,” said Richard B. Lipton, M.D., professor and vice-chair of neurology at the Albert Einstein College of Medicine and director of the Montefiore Headache Center. “Swallowing a pill may make nausea worse and if the patient vomits, medication cannot be absorbed. Nasal sprays are a favored option over tablets in many situations. In addition, many patients dissatisfied with their current acute treatments want faster relief so they can get back to their plans without missing life's important moments. Zavegepant nasal spray will be an important option for patients seeking nonoral therapies and faster relief.”

Biohaven also released an update on its Phase III trial of troriluzole, an investigational therapy for patients with spinocerebellar ataxia (SCA), a group of inherited disorders that cause ataxia or poor muscle control. People with SCA may experience trouble speaking, walking and swallowing.

Depending on the severity of the disease, patients may experience falls, be confined to a wheelchair and lose the ability to communicate. There is no cure and there are currently no FDA-approved treatments for SCA.

The clinical trial used the modified functional Scale for the Assessment and Rating of Ataxia (f-SARA), a 16-point scale that Biohaven developed in collaboration with the FDA, to measure disease progression and drug effect during the study. The trial, which was evaluating the safety and efficacy of the drug, had an endpoint of change in f-SARA from baseline to week 48.

Unfortunately, the endpoint was not statistically significant, which Biohaven attributed to less disease progression than expected. In the overall study population of 213 participants, both the troriluzole and placebo groups had mean baseline scores of 4.9 on the f-SARA. After 48 weeks, there had been very little change, with the troriluzole group having an f-SARA score of 5.1 and the placebo group having a score of 5.2.

One reason for the lack of statistical significance may be due to certain genotypes of SCA. When breaking down the data by genotype, researchers noticed that in participants with the SCA Type 3 (SCA3) genotype, which comprised about 41% of participants in the study, troriluzole demonstrated a greater numerical treatment benefit on the change in f-SARA score from baseline to Week 48 compared to placebo.

"The fact that the overall study population did not show significant disease progression on the f-SARA at 1 year, as would have been anticipated, and failed to meet the study's primary outcome measure, highlight some of the challenges of studying rare diseases such as SCA,” said Biohaven CEO Vlad Coric, M.D. “Given the debilitating nature of this disease, we look forward to sharing the SCA3 genotype data with regulators and working with the FDA to address the high unmet need in this patient population."