Biohaven Eyes FDA Approval for Second Migraine Drug Zavegepant After Promising Trial Results

Biohaven Pharmaceuticals revealed positive top line results from a late-stage trial which show that its migraine medication Zavegepant provides “ultra-rapid” pain relief in just 15 minutes. Zavegepant is similar to Biohaven’s approved migraine pill Nurtec (rimegepant); however, while Nurtec comes as an orally dissolved tablet (ODT), zavegepant is formulated as an intranasal spray.

Results from the study showed that Zavegepant provided migraine pain relief in significantly more individuals compared with placebo. The pain relief effects were sustained for up to 48 hours.

Zavegepant is an antibody drug that prevents binding of the calcitonin gene-related peptide (CGRP) to the CGRP receptor. CGRP receptor antagonists are a new class of antibody drugs used for migraine treatment. Drugs in this class include Eli Lilly’s Emgality (galcanezumab) and AbbVie’s Qulipta (atogepant), which are approved for the treatment of migraine.

While Emgality is administered once a month as an injection for the prevention of migraines, Qulipta is taken orally. Zavegepant has an advantage over the two as it’s the only CGRP receptor antagonist in both intranasal spray and oral pill formulations that is in clinical development for the treatment of acute or episodic migraines. Non-oral formulations have the benefit of having fewer side effects, particularly for patients who suffer from nausea, vomiting or gastroparesis.

Biohaven’s Nurtec ODT is the first and only FDA-approved CGRP receptor antagonist available in a quick-dissolve ODT formulation.

Based on the positive trial data, Biohaven says it plans to file a new drug application (NDA) for Zavegepant with the US Food and Drug Administration (FDA) in the first quarter of 2022.

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Intranasal Zavegepant is an attractive option for migraine patients who need a rapid and non-oral option for acute treatment. Other intranasal sprays for treating migraine headaches include AstraZeneca’s Zolmitriptan, which is among the first selective serotonin receptor agonists for treatment of the neurological ailment.

Zavegepant reversibly blocks the CGRP receptor to prevent CGRP from binding to it. CGRP is a potent vasodilator that is implicated in pain pathways and is mainly released from sensory neurons. Serum levels of CGRP have been shown to be elevated during migraine attacks, and are high in chronic migraine sufferers. As such, targeting CGRP signaling helps provide relief from migraine pain.

Migraines are one of the most common disorders of the nervous system. They are defined as debilitating attacks that last four to 72 hours and that present with symptoms such as pulsating headaches of moderate to severe intensity that can be accompanied by nausea or vomiting, and/or sensitivity to sound (phonophobia) or light (photophobia).

In the US, there are nearly 40 million migraine sufferers. The World Health Organization (WHO) lists migraine as one of the ten most disabling medical illnesses. Over 90 percent of people that suffer from migraines have impaired function and cannot work during an attack.

The safety and efficacy of intranasal Zavegepant were evaluated against placebo for the acute treatment of a moderate or severe migraine attack in a pivotal Phase III clinical trial (NCT04571060). The trial has enrolled over 1,400 adult participants with a history of migraines. The study met its two primary regulatory endpoints of pain freedom and freedom from most bothersome symptoms at two hours that could last up to 48 hours. It had “broad efficacy” as it showed statistically significant superiority over placebo on over a dozen primary and secondary outcome measures. The trial is one of two Phase II/III trials being conducted to evaluate Zavegepant for acute treatment of migraine headaches.

Biohaven did not release the full set of results from the trial and said it will share them at upcoming medical conferences and/or published in peer-reviewed journals.

Biohaven’s first migraine drug Nurtec ODT is approved as both an acute and preventive treatment and has performed above expectations, grabbing sizeable market share and sales. In the third quarter of 2021, Nurtec sales totalled $136 million, a 46 percent jump from the previous quarter. Since its launch in March 2020, the migraine drug has garnered $336 million in sales. Pharma giant Pfizer took notice of its success and shelled out $150 million in cash and purchased $350 million in Biohaven stock to obtain rights to sell Nurtec ODT outside the US.

Moreover, Eli Lilly is trying to give Nurtec a run for its money as it recently launched a Phase IV head-to-head trial evaluating Emgality against Nurtec for the preventative treatment of episodic migraine.