Bioequivalence Study of Sublingual BHV-0223 Shows Positive Results as Rilutek Substitute

José Lopes, PhD avatar

by José Lopes, PhD |

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A dissolving tablet version of riluzole called BHV-0223 has shown positive bioequivalence when compared to the oral form of the therapy, Rilutek, developer Biohaven Pharmaceuticals announced. The dissolving tablet, placed under the tongue, is easier to administrate to patients with amyotrophic lateral sclerosis (ALS) who have trouble swallowing. BHV-0223 also was found to be as effective as Rilutek at a 20 percent lower dose level, which reduces the risk of liver exposure, the company said.

The study sought to show BHV-0223‘s pharmacokinetic equivalence to Rilutek (riluzole), the current standard of care treatment for ALS patients. Pharmacokinetics is the study of the way the body metabolizes, distributes, and excretes a drug. To be approved, BHV-0223‘s effects need to be at least equivalent to Rilutek.

“This is a meaningful advancement for patients with ALS, especially those who would be able to continue taking riluzole despite difficulties swallowing,” Rob Berman, chief medical officer at Biohaven, said in a press release. “In addition, the possibility to achieve a therapeutic exposure with a lower drug dose would make BHV-0223 more amenable to those patients with concerns about liver toxicity.”

Rilutek was the first medication approved by the U.S. Food and Drug Administration (FDA) for the treatment of ALS.

In addition to being problematic for ALS patients with dysphagia, or difficulty swallowing, Rilutek’s protocol for administration is not ideal, as it must be taken at least one hour before, or two hours after, a meal.

Biohaven developed BHV-0223 using Zydis orally dissolving tablet, fast dissolve formulation technology, developed under a global agreement with the company Catalent.

When new drug formulations are made, the FDA requires that bioequivalence studies be conducted. These studies evaluate the pharmacokinetic profile of a new product compared to a reference drug. For a new formulation to be approved, it must be at least as good as the approved one.

In this study, 40 mg of BHV-0223 was compared with 50 mg of Rilutek in 138 healthy volunteers. Topline results showed that BHV-0223 was bioequivalent to Rilutek. BHV-0223 also achieved a similar exposure as Rilutek using a 20 percent lower dose, helping to avoid Rilutek’s adverse liver effects.

Phase 1 clinical trial results already had shown that BHV-0223 is safe and that a 35 mg dose was associated with less variability in the drug’s blood levels than 50 mg of Rilutek.

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

Based on these positive results, the company plans to submit a new drug application (NDA) requesting BHV-0223 to be approved in the first half of 2018.

Biohaven also is advancing its oral, small molecule calcitonin-gene receptor peptide (CGRP) antagonist and glutamate modulation technology platforms for the treatment of migraines, spinocerebellar ataxia, Rett syndrome, and other neuropsychiatric disorders.