The randomized, double-blind, placebo-controlled trial will enroll approximately 2900 people with migraine and will evaluate the efficacy and safety of 100- and 200-mg zavegepant.
Biohaven recently announced that it has enrolled the first patient in a phase 2/3 clinical trial (NCT04804033) of oral zavegepant, its third-generation, highly soluble molecule targeting calcitonin gene-related peptide (CGRP), for the preventive treatment of migraine.1
The company also announced it will receive a $100 million milestone funding payment from Royalty Pharma for the initiation of the phase 3 clinical trial. In August 2020, the 2 companies entered a funding agreement to secure up to $250 million, $150 million of which was already received.
"We are excited to advance the oral formulation of zavegepant into this late-stage, clinical trial and broaden our CGRP franchise. We plan on following the science of CGRP receptor antagonism into pain related disorders and non-migraine indications,” Elyse Stock, MD, chief medical officer, Biohaven, said in a statement. “By expanding beyond our migraine franchise, we are hoping to meet the needs of people impacted by the debilitating aspects of multiple CGRP-mediated diseases.”
Biohaven plans to enroll 2900 participants into the phase 2/3 randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of 100-mg and 200-mg zavegepant. The primary outcome measure will be number of migraine days during weeks 9 to 12, measured by the mean reduction from baseline.
In December 2019, the company announced topline results from another phase 2/3 clinical trial (BHV3500-201; NCT03872453) evaluating the efficacy and tolerability of intranasal zavegepant 5-, 10-, and 20-mg versus placebo in 1673 patients for the acute treatment of migraine.2 At the time, the drug was known as vazegepant, but was eventually revised to zavegepant by the World Health Organization and was accepted by the United States Adopted Names (USAN) Council for use in the US.
Results from the study showed that zavegepant 10 mg and 20 mg was statistically superior to placebo on the co-primary end points of pain freedom and freedom from the most bothersome symptom (MBS, photophobia, phonophobia, or nausea) at 2 hours using single dose.
The benefits of zavegepant were durable and sustained without rescue medication through 48 hours (nominal P <.05). This included sustained pain freedom 2 to 24 hours (5, 10, and 20 mg), sustained pain freedom 2 to 48 hours (5, 10, and 20 mg), sustained pain relief 2 to 24 hours (5, 10, and 20 mg), and sustained pain relief 2 to 48 hours (5 and 10 mg).
Zavegepant demonstrated superiority over placebo on a number of secondary end points that showed its early activity (nominal P <.05). The treatment also had rapid onset with pain relief at 15 minutes (10 and 20 mg), with patients returning to normal function as early as 30 minutes (20 mg). Notably, the 10 and 20 mg doses showed therapeutic benefits on both pain relief and return to normal function at 2 hours.
"We are pleased to see Biohaven progress oral zavegepant into phase 3 for the prevention of migraine, as people suffering from frequent migraines continue to need additional treatment options,” Jim Reddoch, PhD, co-head of Research & Investments, chief scientific officer, Royalty Pharma, said in a statement. “Our successful, multi-year partnership with Biohaven to support both the regulatory approval and commercialization of Nurtec as well as pipeline development is an excellent example of how Royalty Pharma can be a collaborative partner to innovative biopharma companies."1
Zavegepant is structurally distinct from rimegepant (Nurtec ODT), Biohaven’s other GCRP migraine treatment. In February 2020, the FDA approved the use of 75-mg rimegepant in the acute treatment of migraine in adult patients, marking the company’s first agency approval of a product.3