Biohaven Submits IND for Migraine Therapy BHV-3500

September 14, 2018

The third-generation, small molecule CGRP antagonist is the second Biohaven migraine therapy to reach human clinical development.

Charlie Conway, PhD

Biohaven Pharmaceutical has submitted an Investigational New Drug (IND) application to the FDA for its third-generation, small molecule calcitonin gene-related peptide (CGRP) receptor antagonist, BHV-3500.

The therapy, an investigational therapy for the treatment of migraine, 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.

"BHV-3500 has novel properties including high water solubility and a high free fraction which allows for a low dose that we believe is well suited to intranasal delivery," Charlie Conway, PhD, the chief scientific officer of Biohaven, said in a statement.1 "BHV-3500 also exhibits high-affinity binding to the human CGRP receptor with a preference to remain bound to the receptor much longer than unbound, and when paired with intranasal administration has the potential for both rapid onset of action and sustained activity."

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.

The therapy uses the Unit Dose System (UDS) developed by Aptar Pharma, which was designed to allow for the complete delivery of therapies without the need for injection or administration by a healthcare professional. The UDS is approved with multiple drug products marketed in the United States.

"People with migraine seek rapid, long-lasting, convenient, and non-invasive treatments. We are pleased to advance BHV-3500 toward first in human dosing and look forward to expanding our current CGRP platform. BHV-3500's intranasal dosing has the potential to complement rimegepant, which has established efficacy and safety in Phase III clinical trials and provides convenient dual options of a traditional tablet and a rapid dissolving oral formulation," said Elyse Stock, MD, the chief of Portfolio Strategy and Development. "We believe it is important for migraine sufferers to have a range of dosing options for the acute and preventive treatment of migraine and look forward to expanding our CGRP platform with the addition of intranasal delivery and the potential for rapid onset."

Biohaven has already seen clinical success with its other CGRP migraine therapy, rimegepant. It is currently being prepared for a 2019 New Drug Application (NDA) submission to the FDA. Thus far, a pair of phase III trials and a phase IIb trial have been completed. In July, rimegepant data was presented at the American Headache Society annual meeting that revealed the therapy was shown to grant pain freedom to 19.6% of patients after 2 hours, compared to 12% with placebo (P = .0006).2 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).

REFERENCES

1. Biohaven Announces Submission of IND for

BHV

-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 September 13, 2018.

2. 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 of

Migraine

: 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.