Biohaven’s Under-the-Tongue BHV-0223 is One Step Closer to FDA Approval

The U.S. Food and Drug Administration (FDA) has accepted for review the new drug application (NDA) of Biohaven Pharmaceuticals’ BHV-0223, a sublingual (dissolved under the tongue) form of riluzole, as a treatment for amyotrophic lateral sclerosis (ALS).

Biohaven has begun enrollment of ALS patients for its Phase 2/3 clinical trial, which will evaluate whether BHV-0223 behaves in the body in a similar manner as Rilutek, and induces at least equivalent effectiveness and safety results.

More than 80 percent of ALS patients develop dysphagia, or difficulty swallowing, and attempting to swallow medications can lead to aspiration, coughing, choking, pain or discomfort, and difficulties in coordination of swallowing and breathing.

Sublingual BHV-0223 was designed to overcome the limitations of the current FDA-approved formulations of riluzole, which must be swallowed: Sanofi-Aventis’ Rilutek (oral tablet, taken with water) and more recently, ITF Pharma’s Tiglutik (oral thickened liquid).

Besides being problematic for ALS patients with dysphagia, the protocol for administering these formulations is not ideal, as they must be taken at least one hour before, or two hours after, a meal.

BHV-0223 is a lower dose version of riluzole that is placed under the tongue, where it dissolves in seconds and is absorbed into the bloodstream without the need to swallow. It was developed under a worldwide agreement with Catalent, using the company’s Zydis ODT (orally dissolving tablet), fast dissolve formulation technology.

“If approved, we believe BHV-0223 would provide an important advancement in treatment for people living with ALS, including the large number of patients who have difficulty swallowing tablets or liquids,” Robert Berman, MD, Biohaven’s chief medical officer, said in a press release.

The company’s NDA submission of BHV-0223 is supported by data from several studies and clinical trials showing that BHV-0223 is bioequivalent to Rilutek, and generally safe and well-tolerated. In studies in which BHV-0223 was given to patients with ALS and dysphagia, patients preferred the easy-to-use nature of the sublingual form.

In the latest Phase 1 study, the pharmacokinetics — the way the body metabolizes, distributes, and excretes a drug — of sublingual BHV-0223 (40 mg) was compared with that of oral tablets of Rilutek (50 mg) in 138 healthy volunteers. The results showed that BHV-0223 — at a 20% lower dose — achieved similar blood exposures to Rilutek.

With this application, the company expects BHV-0223 will be approved in the first half of 2019.

Early this year, Biohaven established an expanded access program (EAP) with the FDA, in which BHV-0223 is made available for ALS patients, even before its approval.

“We are committed to designing new treatment options for life-altering neurological diseases and believe that our sublingual, orally-dissolving tablet formulation of riluzole can provide a meaningful alternative for people living with ALS,” Berman added.