Biohaven's trial shows positive results for spinocerebellar ataxia drug

Biohaven, previously a part of Biohaven Pharmaceuticals before its acquisition by Pfizer in 2022, has faced numerous challenges with the development of troriluzole, a prodrug of riluzole. Notably, a phase 3 clinical trial in 2022 did not meet its primary endpoints. Despite this setback, the company persisted with the development of the drug, as the trial indicated that patients with type 3 spinocerebellar ataxia (SCA3) – the most prevalent form of the disease – might benefit from the treatment. SCA3 patients comprised 41% of the trial participants.

In 2023, Biohaven submitted a new drug application to the FDA for the use of troriluzole in SCA3 patients. However, the FDA declined the application due to the earlier trial's failure. Biohaven then collaborated with the FDA to create a new, real-world trial. This trial involved 65 individuals with various types of spinocerebellar ataxia who were treated with troriluzole. These participants were compared to two sets of external controls from the US and Europe.

This week, Biohaven announced promising results from this new trial. Over a three-year follow-up period, patients treated with troriluzole experienced a 50-70% reduction in disease progression compared to the external controls who did not receive the treatment. Using the modified Scale for the Assessment and Rating of Ataxia (f-SARA), it was observed that external controls were at least four times more likely to experience a worsening of their condition by two points or more compared to those treated with troriluzole.

Dr. Susan Perlman, director of the ataxia clinic and neurogenetics clinical trials at the David Geffen School of Medicine at UCLA, remarked on the significance of these findings. She noted that spinocerebellar ataxia is a devastating, progressively debilitating disease that severely impacts patients' quality of life, often leaving them unable to perform basic tasks, walk, or speak. Perlman emphasized that troriluzole is the first treatment to demonstrate a delay in disease progression, potentially granting patients additional years of independence and the ability to engage in daily activities.

Spinocerebellar ataxias are a group of rare, inherited neurological disorders characterized by progressive movement difficulties and increasing disability. These diseases, which are caused by various genetic mutations, affect approximately 150,000 people in the United States. Symptoms vary in severity and can be fatal, although patients typically retain cognitive function while losing physical control. Currently, there is no cure for spinocerebellar ataxia, and treatment options are limited, with no FDA-approved therapies specifically targeting the condition.

Riluzole, the drug from which troriluzole is derived, is approved for the treatment of amyotrophic lateral sclerosis (ALS) and similar motor neuron diseases. It has been shown to extend survival in some patients by a few months. Troriluzole, as a prodrug, offers potential advantages in dosing and bioavailability over riluzole.

Following the new trial's positive results, Biohaven intends to resubmit troriluzole to the FDA for the treatment of all spinocerebellar ataxia genotypes by the end of the year. Given the rarity of the disease and the absence of effective treatments, troriluzole qualifies for priority review under FDA orphan drug and fast-track status.