FDA Accepts NDA Filing of BHV-0223 for Treatment of ALS

Robert Berman, MD,Chief Medical Officer of Biohaven

Robert Berman, MD

Biohaven Pharmaceutical announced that its 505(b)(2) new drug application for BHV-0223, an investigational sublingual form of riluzole for treatment of amyotrophic lateral sclerosis (ALS), has been accepted for review by the FDA.

BHV-0223 is a novel, low dose Zydis formulation of riluzole that is administered sublingually; in December 2016 it was granted orphan drug designation by the FDA. Riluzole, the active ingredient, is the only FDA-approved treatment to extend tracheostomy-free survival in those with ALS. Existing formulations of riluzole consist of only an oral tablet (Rilutek) taken with water or an oral suspension.

“We are extremely proud to announce the FDA acceptance for review of our 505(b)(2) new drug application submission of BHV-0223, as it represents Biohaven’s first NDA. 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, chief medical officer, Biohaven, said in a statement.¹ “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.”

The new drug application submission is backed by data from multiple studies and clinical trials that evaluated the bioequivalence of BHV-0223 to riluzole oral tablets as well as the safety and tolerability of BHV-0223.

The main data from the clinical program designed to demonstrate pharmacokinetic equivalence of sublingual BHV-0223 compared to oral riluzole confirmed that sublingual administration of BHV-0223 (40 mg) achieved similar blood exposures to orally ingested riluzole (50 mg) but with a 20% lower total daily drug burden.² The results were reported in a bioequivalence study where 138 healthy volunteers were administered BHV-0223 and oral riluzole under fasted conditions. In the pre-specified primary analysis, BHV-0223 achieved area-under-the-curve and peak exposures of approximately 90% and 113%, respectively, compared to those generated by oral riluzole.² BHV-0223 was generally well tolerated and participants reported that the sublingual formulation was easy to use. Based on the study results and reduced drug exposure to the liver, BHV-0223 may have a lessened risk for causing liver test elevations.

Biohaven previously received regulatory feedback from the FDA that the section 505(b)(2) pathway was acceptable for BHV-0223 in ALS and that no additional efficacy or toxicology studies after the bioequivalence study were necessary for submission of a new drug application.

In May, Biohaven announced that it established an expanded access program (NCT03537807) with sublingual BHV-0223 for those with ALS. Through the program, physicians can obtain BHV-0223 for eligible patients with ALS at no cost. The open-label program is available for up to approximately 250 adult patients with ALS who have difficulty swallowing oral riluzole tables and may receive benefit from treatment with an alternative oral formulation of riluzole.

REFERENCE

1. Biohaven Announces FDA Acceptance of 505(b)(2) NDA Filing for

BHV

-0223, a Novel Sublingual Delivery Form of Riluzole for the Treatment of Amyotrophic Lateral Sclerosis (ALS) [news release]. New Haven, Conn.: Biohaven Pharmaceutical Holding Company Ltd.; 2018. https://www.prnewswire.com/news-releases/biohaven-announces-fda-acceptance-of-505b2-nda-filing-for-bhv-0223-a-novel-sublingual-delivery-form-of-riluzole-for-the-treatment-of-amyotrophic-lateral-sclerosis-als-300754924.html. Accessed Nov. 26, 2018.

2.

Biohaven Announces Positive Results from Bioequivalence Study with Sublingual

BHV

-0223 Zydis Orally Dissolving Tablet [news release]. New Haven, Conn.: Biohaven Pharmaceutical Holding Company Ltd.; 2018. https://www.biohavenpharma.com/investors/news-events/press-releases/01-09-2018. Accessed Nov. 26, 2018.