FDA OKs Biohaven’s Sublingual BHV-0223 for Clinical Investigation

The U.S. Food and Drug Administration (FDA) has given the green light to Biohaven Pharmaceuticals to advance sublingual BHV-0223, which regulates glutamate communication between neurons, into clinical trials for amyotrophic lateral sclerosis (ALS) patients.

The FDA’s  permission to go ahead with the study followed Biohaven’s submission of an investigational new drug (IND) application.

“Our goal is to establish the bioequivalence of BHV-0223 to its active pharmaceutical ingredient, riluzole, with our new sublingual and lower dose formulation,” Vlad Coric, MD, chief executive officer of Biohaven, said in a press release. “If we successfully establish bioequivalence in the upcoming trial and demonstrate the advantages of this formulation to patients, we expect to 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,” Coric added.

To establish bioequivalence, researchers will compare the effects of BHV-0223 with riluzole, which is BHV-0223’s major chemical component and is already FDA-approved for ALS in tablet form.

Rilutek (riluzole) remains the only approved treatment for people with ALS. It has only marginal effects on survival and must be swallowed, which is not ideal for ALS patients, who often have difficulty swallowing. Rilutek also should be taken at least one hour before, or two hours after, a meal.

“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,” said Irfan Qureshi, MD, executive director of neurology at Biohaven.

BHV-0223 uses the Zydis oral disintegrating tablet, fast-dissolve, dosing technology developed under an exclusive worldwide agreement with Catalent. With this technology, the company expects to overcome the limitations of riluzole tablets and improve patients’ ability to adhere to medication schedules.

In December 2016, the FDA granted the company orphan drug designation for BHV-0223 for the treatment of ALS. Biohaven has also received regulatory feedback from the FDA stating that after this study, no additional efficacy or toxicology studies are needed for BHV-0223’s approval.

Biohaven also is advancing its oral, small molecule calcitonin-gene related peptide (CGRP) antagonist and glutamate modulation technology platforms, which could help patients with other conditions such as migraines, spinocerebellar ataxia, Rett syndrome, and other neuropsychiatric disorders.

CGRP receptor antagonists (small molecules that counteract the action of CGRP) have been shown to block migraines. Currently, the company has two CGRP antagonists in its pipeline. Rimegepant (BHV-3000) is being evaluated in an ongoing Phase 3 trial for the treatment of acute migraines. Biohaven also will be submitting an application to advance BHV-3500 into clinical trial by year’s end to prevent chronic and episodic migraines.