Biohaven’s real-world trial shows positive results for spinocerebellar ataxia drug

Biohaven, which spun out​ of Biohaven Pharmaceuticals in 2022 when its parent company was acquired by Pfizer, has had a number of setbacks in the development of troriluzole –a prodrug of riluzole– including a phase 3 trial failure in 2022.

However, the company continued development, as results of the failed phase 3 trial showed that patients with the most common kind of spinocerebellar ataxia, known as type 3, who made up 41% of the trial group, did appear to benefit from troriluzole.

In 2023, Biohaven submitted a new drug application to the FDA for troriluzole in patients with type 3 spinocerebellar ataxia, but the regulator refused to file​ the application based on the drugs earlier trial failure.

The company then worked with the FDA to design a new, ‘real-world’ trial that compared 65 spinocerebellar ataxia patients (all types) given troriluzole to two sets of matched external controls in the US and Europe.

The results​ announced this week show troriluzole treated patients had a 50-70% slowing of disease progression compared with the external untreated controls over 3 years of follow up.

Using the modified functional Scale for the Assessment and Rating of Ataxia (f-SARA) external controls were at least 4 times more likely to have a 2 point or greater worsening of their disease than patients treated with troriluzole.

"SCA is a debilitating, relentlessly progressive disease that destroys quality of life, leaving patients unable to care for themselves, walk, or speak,” said Susan Perlman, director of the ataxia clinic and neurogenetics clinical trials at the David Geffen School of Medicine at UCLA, in a press statement about the trial.

“Troriluzole is the very first treatment to show a delay in disease progression that can give patients additional years of independence, where they can walk without assistance, continue to work, play with their children, and participate in daily activities. This is an exciting and hopeful moment for the SCA community."

Fighting for a treatment​

Spinocerebellar ataxias are a group of rare progressive, inherited neurological diseases that affect movement and result in increasing disability over time. There are many types of spinocerebellar ataxias, defined by the genetic cause, and they are estimated to affect around 150,000 people in the US.

Due to the heterogeneity of genetic mutations causing this condition the symptoms vary in severity but can be fatal. Most often, patients retain mental capacity, but gradually lose physical control of movement. No cure exists for spinocerebellar ataxia and limited treatments addressing the symptoms are available, with no FDA approved therapies specifically designed for treating spinocerebellar ataxia.

Riluzole is approved to treat amyotrophic lateral sclerosis (ALS) and similar motor neuron diseases and has been shown to increase survival in some patients by several months. Troriluzole is a prodrug of riluzole and may have dosing advantages and better bioavailability than riluzole.

Based on the new trial results, Biohaven now plans to resubmit troriluzole to the US Food and Drug Administration (FDA) for treatment of all SCA genotypes before the end of the year. Due to the lack of treatments and rare nature of the disease, troriluzole is eligible for priority review because it has FDA orphan drug and fast-track status.