- The Food and Drug Administration rejected an application from Biohaven Pharmaceuticals for approval of its ALS drug, citing manufacturing quality issues with the active pharmaceutical ingredient used in a 2017 study, the biotech disclosed Friday.
- Biohaven said the sole issue raised by the FDA was over manufacturing concerns involving an Indian subsidiary of the Canadian generic drugmaker Apotex. Neither company responded to BioPharma Dive's request for comment by time of publication.
- Biohaven had sought approval for a sublingual version of riluzole that it dubbed Nurtec. Riluzole was first approved by the FDA in 1995 under the brand name Rilutek and remains standard treatment for ALS patients. Generic versions have dominated the market since the first copycat was OK'd in 2013.
Apotex produced the active pharmaceutical ingredient, or API, for Nurtec from 2014 to 2016. Biohaven then used that supply in a 2017 bioequivalence study that was part of its application packet to the FDA.
In announcing the Complete Response Letter from the FDA, Biohaven's leaders cast the blame squarely on Apotex. The New Haven, Connecticut-based biotech said the FDA had given recommendations to Apotex on information needed to qualify certain API batches, but Apotex never told Biohaven about that regulatory communication.
"We are doing everything possible to work with the FDA and the API manufacturer to resolve this matter, which we believe to be more technical in nature," Robert Berman, Biohaven's chief medical officer, said in a July 20 statement.
"We believe that the quality issues surrounding the Apotex manufacturing facility do not affect the conclusions of our bioequivalence study, but will work collaboratively with the FDA to resolve this matter as quickly as possible."
Nurtec's API for commercial supply comes from a different supplier, according to the company.
Manufacturing concerns commonly trip up drug applications submitted to the FDA. Similar rejections in the past few months include those for Heron Therapeuticbhs' non-opioid painkiller, Nabriva Therapeutics' complicated urinary tract infection medication and Acacia Pharma's experimental drug for post-operative nausea and vomiting.
Biohaven's stock was little changed Monday morning, reflecting the marginal value Wall Street analysts and investors have assigned to Nurtec. The vast majority of the company's value stems from its experimental migraine drug, rimegepant.
But Biohaven has said it believes Nurtec can differentiate itself from generic riluzole, given its sublingual formulation. About one-third of ALS patients have difficulty swallowing at time of diagnosis, and a vast majority have trouble as the disease progress to advanced stages. Roughly 5,000 Americans are diagnosed each year with amyotrophic lateral sclerosis, according to the ALS Association.
About half of Americans clinically diagnosed with ALS are treated with riluzole, according to Biohaven's company presentation.
The biotech did not specify a timeline for resubmission. Cantor Fitzgerald analyst Charles Duncan expects clarity on timing by the end of September, he wrote in a Monday note to investors.