Biohaven—addressing neurological disorders

With several products in advanced clinical stages, such as oral CGRP-receptor antagonists and glutamate modulators, Biohaven is welcoming collaborations on these programs and broadening its pipeline further.

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Biohaven Pharmaceuticals, Inc., is a clinical-stage biopharmaceutical company with a portfolio of innovative, late-stage product candidates target­ing neurological diseases. The compounds are oral small molecules based on two distinct mechanistic platforms: calcitonin gene-related peptide (CGRP)- receptor antagonists, and glutamate modulators. Both therapeutic strategies could affect approaches to a diverse set of unmet needs. 

Biohaven’s lead compounds are the CGRP-receptor antagonist rimegepant and the glutamate modulator trigriluzole (BHV-4157). Rimegepant, an oral formula­tion for the treatment of acute migraine, is in two phase 3 clinical trials; topline results are expected in the first quarter of 2018. Trigriluzole is in development for the treatment of ataxias, obsessive-compulsive disorder and Alzheimer’s disease.

In addition, Biohaven has several other programs in development, including a CGRP-receptor antago­nist for episodic and chronic migraine, and glutamate modulators for multiple neurologic and neuropsychi­atric disorders (Fig. 1).

“Biohaven’s goal is to build a broad portfolio of best-in-class and first-in-class therapies for severe neuro­logic disorders,” said Vlad Coric, CEO of Biohaven. “As we continue to make rapid clinical progress across both our lead technology platforms, we are also seeking new opportunities to bring patients the next generation of novel and innovative treatments.”

Figure 1: Biohaven Pharma’s portfolio of innovative, late-stage neurology assets. The company’s smallmolecule product candidates represent two distinct therapeutic strategies—calcitonin gene-related peptide (CGRP)-receptor antagonists and glutamate modulators—with the potential to affect treatment approaches.

Taking on migraine

Migraine is a debilitating condition that alters a per­son’s daily activities. The most common migraine symptoms are pulsating moderate-to-severe head­aches, nausea, sensitivity to light (photophobia) and sound (phonophobia), and visual disturbances. Migraine is the world’s third most prevalent illness and seventh highest specific cause of disability.

Triptans, the current standard of care for migraine, are a class of serotonin 5-HT1B/1D–receptor ago­nists that constrict blood vessels in the brain and relieve swelling. But the class is contraindicated in patients at risk of cardiovascular events because of its vasoconstrictive properties. In addition, triptans are associated with headache recurrence and medi­cation-misuse headaches. Biohaven’s rimegepant is an investigational agent that targets the mechanisms at the root of migraine.

Rimegepant is an oral CGRP-receptor antagonist that suppresses pain transmission between neu­rons. In addition, CGRP-receptor inhibition blocks the pathologic dilation of arteries without relying on active vasoconstriction, thus precluding the side effects of triptans. The overall effect is a reduction in neurogenic inflammation.

This novel mechanism, combined with the drug’s oral bioavailability and high potency at the CGRP receptor, make rimegepant a potential best-in-class molecule for the treatment of acute migraine. Rimegepant offers patients a ‘whenever, wherever’ ease of self-administration, in contrast to the need for intravenous infusion or subcutaneous needle admin­istration of CGRP-targeting monoclonal antibodies.

The intellectual property rights for rimegepant are in-licensed from Bristol-Myers Squibb and are covered by five families of patents. Rimegepant has been dosed in almost 700 subjects and studied in six clinical trials in healthy volunteers and in patients with migraine, and has shown effectiveness against the most common migraine symptoms. In a phase 2b trial, rimegepant demonstrated comprehensive and durable treatment effects in acute migraine.

Glutamate modulation: a proven mechanism

Glutamate plays an essential role in 90% of all brain synapses, and dozens of severe disorders can be traced to glutamate dysregulation. These include Alzheimer’s disease, anxiety disorders and other neurologic diseases.

At Yale University, and later at Biohaven, the team led by Coric advanced trigriluzole, a third-generation tri­peptide prodrug of riluzole, into the clinic. Trigriluzole has high oral bioavailability, bypasses first-round metabolism and is not associated with a negative food effect, which maximizes its therapeutic impact and addresses most limitations of riluzole. Biohaven has filed several US and international patent applications covering trigriluzole and other prodrugs of riluzole.

“We believe that trigriluzole represents a potential best-in-class glutamate modulating compound for the potential treatment of a number of neuropsychi­atric disorders and could provide a robust alternative to riluzole in ALS,” said Coric.

Partnering forward

As Biohaven continues to drive the completion of its clinical programs, the company also welcomes discus­sions toward broadening its pipeline of highly inno­vative drug candidates for neurologic disorders. The company’s broad experience with the development of new solutions for neurologic disorders, including a number of orphan diseases, makes Biohaven a part­ner of choice for potential collaborators interested in expanding their own reach and impact in the space.


Vlad Coric, CEO
Biohaven Pharmaceuticals, Inc.
New Haven, Connecticut, USA
Tel: +1-203-404-0410

Go to the profile of Biohaven Pharmaceuticals

Biohaven Pharmaceuticals

Biohaven is a clinical-stage biopharmaceutical company with a portfolio of innovative, late-stage product candidates targeting neurological diseases, including rare disorders. Our product candidates are small molecules based on two distinct mechanistic platforms—calcitonin gene-related peptide, or CGRP, receptor antagonists and glutamate modulators—which we believe have the potential to significantly alter existing treatment approaches across a diverse set of neurological indications with high unmet need in both large markets and orphan indications. The most advanced product candidate from our CGRP receptor antagonist platform is rimegepant, which we are developing for the acute treatment of migraine and for which we intend to initiate two Phase 3 clinical trials in the second half of 2017. The most advanced product candidate from our glutamate modulation platform is trigriluzole, which we are developing for the treatment of ataxias with an initial focus on spinocerebellar ataxia, or SCA. We have received orphan drug designation from the FDA for trigriluzole in SCA, and we began a Phase 2/3 clinical trial in SCA in December 2016 and expect to report topline results in early 2018. Our second most advanced product candidate from our glutamate modulation platform is BHV-0223, which we are developing for the treatment of amyotrophic lateral sclerosis, or ALS, a neurodegenerative disease that affects nerve cells in the brain and spinal cord. We have received orphan drug designation from the FDA for BHV-0223 in ALS.

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