Biohaven ALS drug blocked by FDA over manufacturing issue

Biohaven’s therapy for amyotrophic lateral sclerosis (ALS) has been rejected by the FDA over manufacturing compliance issues for its active ingredient.

The US regulator is concerned about a bioequivalence study for the riluzole compound used in the new Nurtec oral formulation – designed to dissolve under the tongue – which was carried out using an active ingredient sourced from generic drugmaker Apotex.

The riluzole in Biohaven’s current formulation doesn’t come from Apotex, but serious compliance issues at the latter company’s manufacturing plants in India have cast the results of that 2017 study into doubt, resulting in a complete response letter (CRL) turning the marketing application down.

Biohaven insists that it has not used Apotex riluzole in its current Nurtec formulation, which is provided by another supplier with no compliance issues. Concerns with Apotex manufacturing led to the official withdrawal of 31 of its drug products from the US market last week.

The company played down the rejection in a prepared statement, saying that the FDA had no other issues with its marketing application and that it had “already submitted additional information to the FDA regarding this issue.”

Nurtec isn’t considered to be a big earner for Biohaven even if approved, as it is a new formulation of an active drug that has been available for years to treat ALS in a regular tablet formulation. Originally developed by Sanofi and first approved as Rilutek in 1995, low-cost generics have been available in the US for several years.

After news of the CRL emerged, analysts at Cantor Fitzgerald said it does not affect Biohaven’s valuation, which is more closely tied to oral CGRP inhibitor drug rimegepant in late-stage for acute migraine treatment, migraine prevention and other indications including refractory trigeminal neuralgia. That drug is however up against competition from oral CGRP rivals from Allergan (ubrogepant and atogepant) and Eli Lilly (lasmiditan) which are also in late-stage testing.

Shortly after the rejection, Biohaven issued another statement pointing to progress with another of its pipeline programmes, riluzole prodrug troriluzole, saying it expects to have a phase 2/3 trial in Alzheimer’s disease fully enrolled by the end of the year. Troriluzole is also in mid-stage testing for anxiety and obsessive-compulsive disorder.

Cantor analyst Charles Duncan said in a research note that he does not expect the CRL to have an impact on any of Biohaven’s other pipeline candidates.