Biohaven fails OCD trial but pushes on to phase 3 regardless

A phase 2/3 trial of Biohaven Pharmaceutical’s troriluzole in obsessive-compulsive disorder (OCD) has missed its primary endpoint. Despite the setback, Biohaven is gearing up for a full phase 3 OCD program, pointing to other aspects of the midstage data to make its case. 

In February, Biohaven stopped developing glutamate-targeting prodrug troriluzole as a single agent in generalized anxiety disorder in response to the failure of a phase 3 trial in the indication. Biohaven continued pushing forward in indications including OCD and Alzheimer’s disease, though, in the belief cutting synaptic levels of glutamate will improve outcomes in those diseases. 

The phase 2/3 OCD readout gave Biohaven a chance to generate data to validate that belief. In the end, the phase 2/3 failed to alleviate doubts about whether Biohaven can bring troriluzole to market.

After 12 weeks of daily dosing, the Yale-Brown Obsessive-Compulsive Scale scores of participants in the troriluzole arm were statistically no better than those of their peers on placebo. Scores in the treatment group fell 5.9 points from baseline, compared to a 4.9 drop in the placebo cohort.

The failure to beat placebo at the 12-week mark caused the trial to miss its primary endpoint. Yet Biohaven found cause for optimism in the 8-week data. At that point, the 1.5-point gap in the scores of the treatment and control groups amounted to a statistically significant difference. Troriluzole and placebo performed comparably at the 4-week mark.

As Biohaven sees it, the “results reveal a consistent treatment benefit of troriluzole over time.” That conclusion, coupled to some other factors, led Biohaven to commit to a phase 3 program in OCD.

Biohaven plans to include a higher-dose arm in the phase 3. The phase 2/3 trial used a 200 mg dose. An ongoing phase 2/3 Alzheimer’s trial is testing a 280 mg dose. Biohaven said troriluzole was “well-tolerated with a safety profile consistent with past clinical trial experience” in the OCD study.

The addition of a high-dose arm is just one of the changes Biohaven is considering. Biohaven R&D VP Loren Aguiar said in a statement that work is underway to “further minimize placebo effect” for the phase 3 program.

There is also scope for Biohaven to improve the chances of success by targeting a subgroup of OCD patients. The divergence between the treatment and control results was larger in a subpopulation of participants who were severely ill at baseline, although even in that analysis troriluzole only achieved statistical significance over placebo in the 8-week data. 

Biohaven now plans to hold a meeting with the FDA ahead of the initiation of a pivotal phase 3 trial. Shares in Biohaven slipped a few percentage points in premarket trading, but the stock remains near its all-time high. Biohaven won FDA approval for its small molecule CGRP receptor antagonist in the treatment of acute migraines earlier this year.