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The phase 2 trial for the CGRP receptor agonist is planned for Q2 of 2019 after the intranasal treatment met its target therapeutic exposures in phase 1. Biohaven submitted an IND to the FDA in September 2018.
Vlad Coric, MD
Biohaven Pharmaceuticals has announced that its investigational, intranasally administered calcitonin gene-related peptide (CGRP) receptor agonist, BHV-3500, has achieved its targeted therapeutic exposures and will be advancing into a phase 2 trial to evaluate its efficacy in the acute treatment of migraine.1
The phase 1 trial explored a “broad dose range,” according to Biohaven, in order to characterize the pharmacokinetic profile and initial safety of the agent in humans. In September 2018, the manufacturer submitted an Investigational New Drug (IND) application to the FDA for BHV-3500.
The phase 2 trial of BHV-3500 is planned to begin in the second quarter of 2019.
"We are excited to report that intranasal administration of BHV-3500 in our Phase 1 trial achieved drug exposures that we believe will be therapeutic in the acute treatment of migraine,” Vlad Coric, MD, CEO of Biohaven, said in a statement. “Additionally, the PK profile of intranasal BHV-3500 demonstrated the earliest Tmax that we have observed with a small molecule CGRP receptor antagonist and suggests the potential for an ultra-rapid onset of action without the need for an injection.”
BHV-3500 utilizes the Unit Dose System (UDS) from Aptar Pharma, which is designed to enable the administration of treatments without the need for injection or direction of a health care professional. The UDS is approved by the FDA for a number of products in the United States.
The therapy is the second compound of its kind from Biohaven to reach this stage of development and be introduced to the clinic as an intranasal formulation. The other therapy in its pipeline is rimegepant. In proof-of-concept preclinical data, BHV-3500 was observed in marmoset assay with oral delivery, without any cardiovascular safety or systemic toxicity issues seen. Its structure, distinct from rimegepant, was developed to make it potentially suitable as an inhaled, intranasal, oral, or subcutaneous therapy.
“BHV-3500 is complementary to our lead migraine asset rimegepant, which has shown efficacy and safety in 3 phase 3 clinical trials. We are now a step closer to our goal of providing migraine sufferers with a range of noninvasive, CGRP receptor antagonist dosing options for both the acute and preventive treatment of migraine," Coric added.
At the time of the IND submission, Elyse Stock, MD, the chief of Portfolio Strategy and Development at Biohaven said that due to the need for rapid, long-lasting, convenient, and non-invasive treatments for patients with migraine, BHV-3500 holds the potential to complement rimegepant as a treatment duo.2
Rimegepant is currently being prepared for a 2019 New Drug Application (NDA) submission to the FDA. Thus far, 2 phase 3 trials and a phase 2b trial have been completed. Data was presented at the American Headache Society 2018 annual meeting which showed rimegepant granted pain freedom to 19.6% of patients after 2 hours, compared to 12% with placebo (P = .0006). As well, freedom from the most bothersome symptom, photophobia, was achieved by 37.6% of the rimegepant group compared to 25.2% of the placebo group (P <.0001).3
Robert Croop, MD, Biohaven's Chief Development Officer of Neurology, added, "We are pleased to advance our next generation of CGRP receptor antagonist into further clinical development. If approved, this important component of our NOJECTION™ platform potentially offers patients a simple to use intranasal formulation in this new approach to treating migraine. We believe that intranasal BHV-3500 may provide people with migraine rapid onset of relief in a form that can easily be self-administered whenever and wherever a migraine strikes."
1. Biohaven Achieves Targeted Therapeutic Exposures of BHV-3500, a Third-Generation Small Molecule CGRP Receptor Antagonist [press release]. New Haven, CT: Biohaven Pharmaceuticals; Published February 4, 2019. prnewswire.com/news-releases/biohaven-achieves-targeted-therapeutic-exposures-of-bhv-3500-a-third-generation-small-molecule-cgrp-receptor-antagonist-300788789.html. Accessed February 4, 2019.
2. Biohaven Announces Submission of IND forBHV-3500, Third-Generation, Small Molecule CGRP-Receptor Antagonist for the Treatment of Migraine [press release]. New Haven, CT: Biohaven Pharmaceutical Holding Company Ltd.; Published September 12, 2018. biohavenpharma.com/biohaven-announces-submission-of-ind-for-bhv-3500-third-generation-small-molecule-cgrp-receptor-antagonist-for-the-treatment-of-migraine. Accessed February 4, 2019.
3. Lipton RB, Coric V, Stock EG, et al. Efficacy, Safety, and Tolerability of Rimegepant 75 mg, an Oral CGRP Receptor Antagonist, for the Acute Treatment ofMigraine: Results from a Double-Blind, Randomized, Placebo-Controlled Trial, Study 302. Presented at: 2018 American Headache Society annual meeting; June 27 - July 1, 2018. San Francisco, CA. Abstract IOR-02LB.