Biohaven Pharmaceutical announced it enrolled the first patient in a Phase 2/3, double-blind, randomized, placebo-controlled, dose-ranging trial of intranasally administered BHV-3500 for the acute treatment of migraine. BHV-3500 is a novel, structurally distinct, third-generation calcitonin gene-related peptide (CGRP) receptor antagonist being developed by Biohaven.
In the trial, three doses of BHV-3500 (5, 10 and 20 mg) are being compared to placebo in the treatment of a migraine attack. With a planned enrollment of approximately 400 randomized subjects per treatment arm, the trial is powered to provide proof of efficacy on the regulatory endpoints of pain freedom and freedom from the most bothersome migraine-associated symptom at 2 hours post-dose. The trial is also designed to detect early onset of other clinical measures that are of great importance to patients, including pain relief and ability to return to normal functioning.
"This is the first late-stage clinical trial designed to assess the efficacy of an intranasally administered CGRP receptor antagonist in the acute treatment of migraine,” Vlad Coric, M.D., CEO of Biohaven, said. “The PK profile from our recently completed Phase 1 trial suggests the potential for an ultra-rapid onset of action without the need for an injection. BHV-3500 is complementary to our lead migraine asset, rimegepant, which has met the primary efficacy endpoints in three completed Phase 3 clinical trials, with a favorable safety profile. We believe that intranasal BHV-3500 may provide people with ultra-rapid onset of migraine relief in a form that can easily be self-administered whenever and wherever a migraine strikes."
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Intranasal BHV-3500 utilizes the Aptar Pharma Unit Dose System (UDS), which is designed to enable systemic delivery of drugs without the need for injection or administration by a healthcare professional. This device is FDA-approved to deliver multiple drug products marketed in the U.S., and is used by thousands of people every day. The Phase 1 trial used the Aptar Pharma UDS device and maintains important consistency of dosing throughout the BHV-3500 clinical development program. Catalent Pharma Solutions completes the fill/finish manufacturing of BHV-3500 and assembles the Aptar intranasal devices for Biohaven's clinical trials.
"We are excited to advance BHV-3500, our third-generation CGRP receptor antagonist, into this Phase 2 trial to assess the best dose to move forward into a pivotal trial,” Robert Croop, M.D., Biohaven's Chief Development Officer – Neurology, said. “The PK profile and intranasal administration differentiates BHV-3500 from other CGRP antagonists and may provide patients with an important new treatment option."
BHV-3500 is the second of Biohaven's CGRP receptor-targeting compounds to enter clinical trials. Biohaven's multiple CGRP receptor antagonist product candidates, including rimegepant, and expanded array of formulations including intranasal delivery and Catalent's Zydis® oral fast-dissolve tablet, are designed to meet patients' needs across the spectrum from acute to preventive treatment of migraine.
BHV-3500, the second product candidate in Biohaven's NOJECTION™ migraine platform, is a high affinity small molecule CGRP receptor antagonist with favorable potency and low protein binding. It is structurally distinct from rimegepant. The physicochemical properties of BHV-3500 make the drug candidate potentially suitable for multiple routes of delivery, including nasal, inhalation or oral administration. It is initially being developed as an intranasal formulation for the acute treatment of migraine.
Over 36 million Americans suffer from migraine. Acute attacks of migraine can differ in intensity and frequency, with many being highly disabling. More than 90 percent of migraine sufferers are unable to work or function normally during an attack. In the Global Burden of Disease Study, updated in 2015, migraine was ranked as the seventh highest cause worldwide of years lost due to disability. CGRP receptor antagonists represent a novel class of drug candidates for the treatment of migraine and are the first new class specific to the acute treatment of migraine in over 25 years. This unique and specific mode of action potentially offers an alternative to current agents, particularly for patients who have contraindications to the use of triptans, such as those with underlying cardiovascular diseases, or who either do not respond or have inadequate or inconsistent response to triptans or are intolerant to them.