Biohaven Pharmaceutical Holding Company and its wholly owned subsidiary, Biohaven Pharmaceuticals, announced that the US Food and Drug Administration (FDA) has notified the Company that it may proceed with its clinical investigation of sublingual BHV-0223 as a potential treatment for patients with Amyotrophic Lateral Sclerosis (ALS). The FDA clearance to proceed was received following Biohaven's submission of an investigational new drug (IND) application for this program, and the Company expects to commence a bioequivalence study of BHV-0223 in the current quarter. Biohaven previously received regulatory feedback from the FDA that the Section 505(b)(2) pathway is acceptable for BHV-0223 in ALS, and that beyond this study, no additional efficacy or toxicology studies will be necessary for the submission of a new drug application (NDA).

BHV-0223 is an innovative sublingually administered and orally dissolving tablet (ODT) formulation of riluzole, a glutamate modulating agent, which is designed to advance beyond the current limitations of riluzole tablets. While riluzole tablets are FDA approved for ALS, they may be difficult to administer in ALS patients, who typically have difficulty in swallowing.  The tablets also have certain pharmacokinetic (PK) and pharmaceutic limitations including being associated with a negative food effect that lowers drug levels.  BHV-0223 is unique in that it utilizes the Zydis ODT fast-dissolve, dosing technology developed under an exclusive worldwide agreement with Catalent. In previous clinical studies, BHV-0223 was associated with less PK variability than riluzole tablets.

BHV-0223 is one of the lead drug candidates in Biohaven's glutamate modulation technology platform being developed across several therapeutic indications.  Agents that modulate glutamate neurotransmission may have therapeutic potential in multiple disease states involving glutamate dysfunction, including ALS, Alzheimer's disease, Rett syndrome, dementia, dystonia, ataxias, tinnitus, anxiety disorders, and affective disorders like major depressive disorder.

Vlad Coric, M.D., chief executive officer of Biohaven, commented, "Our goal is to establish the bioequivalence of BHV-0223 to its active pharmaceutical ingredient, riluzole, with our new sublingual and lower dose formulation.  If we successfully establish bioequivalence in the upcoming trial and demonstrate the advantages of this formulation to patients, we  expect be in position for an NDA submission.  ALS is a serious neurodegenerative disorder for which there are few treatment options, and we believe that the significant improvements gained through enhanced formulation, dosage and route of administration of BHV-0223 may benefit patients with this devastating disease."

"BHV-0223 is designed to meet the needs of patients with ALS," said Irfan Qureshi, M.D., Executive Director, Neurology at Biohaven. "Progressive difficulty with swallowing is one of the most common and debilitating problems caused by ALS. Attempting to swallow standard medication tablets can lead to impaction, aspiration, coughing, choking, pain or discomfort, and problems coordinating swallowing and breathing. BHV-0223 seeks to address this challenging issue by instead being placed under the tongue where it rapidly dissolves and is absorbed into the systemic circulation without the need for swallowing."

Beyond its planned bioequivalence study of BHV-0223 in ALS, Biohaven is making progress across its oral, small molecule calcitonin-gene related peptide (CGRP) antagonist and glutamate modulation technology platforms.

In its CGRP antagonist platform, enrollment and randomization continue to proceed efficiently in both of Biohaven's phase 3 clinical trials of rimegepant for the acute treatment of migraine.  The Company expects to end enrollment before the 2017 year end and report topline results in the first quarter of 2018. Data from the ongoing long-term safety study is expected to support a potential NDA submission in the first half of 2019. Biohaven also expects to submit an IND to the FDA by the end of this year for BHV-3500 for the treatment of migraine.

With regard to other assets in its glutamate modulating platform, the Company expects to initiate a Phase 2/3 trial examining the efficacy and safety of trigriluzole in obsessive-compulsive disorder (OCD) in the fourth quarter of 2017. Biohaven is also continuing a long-term (48-week) extension study of trigriluzole in patients with spinocerebellar ataxia (SCA) and plans on regulatory interactions early in 2018 to discuss continued development in the ataxias. With regard to BHV-5000, a low trapping NMDA receptor antagonist in-licensed from AstraZeneca AB, the Company continues to optimize its formulation to support a phase 1 pharmacokinetic trial in Rett syndrome, as well as other neuropsychiatric indications.