Biohaven Prepares for Comeback With Key Spinocerebellar Ataxia Study Results

On Monday, Biohaven revealed key data from its pivotal trial for the drug candidate troriluzole, demonstrating significant symptomatic and functional improvements in patients with spinocerebellar ataxia (SCA). The company reported that treatment with troriluzole resulted in a "robust and clinically meaningful slowing of disease progression," with the investigational treatment reducing patients' rate of decline by 50% to 70% compared to those who were untreated. This effect translated to a delay in disease progression by approximately 1.5 to 2.2 years over the course of the three-year study.

The trial utilized the modified functional Scale for the Assessment and Rating of Ataxia (f-SARA) tool, which measures disease progression by at least a two-point worsening in score. According to Biohaven, untreated patients were more than four times as likely to experience disease progression compared to those on troriluzole. CEO Vlad Coric highlighted that the SCA program, encompassing this pivotal study, has provided the first evidence of a clinically meaningful treatment benefit and a slowdown in disease progression for SCA patients. Coric emphasized the urgency for treatments for this devastating neurodegenerative disease and expressed the company's eagerness to engage with regulatory agencies to make troriluzole available to SCA patients.

Biohaven is preparing to submit a New Drug Application (NDA) in the fourth quarter of 2024, supported by the recent trial results and prior efficacy and safety data. SCA is a group of inherited neurodegenerative disorders characterized by the progressive loss of voluntary muscle control, leading to the atrophy of crucial parts of the nervous system, such as the cerebellum, brainstem, and spinal cord. Patients typically face compromised motor skills, increased risk of falls, speech impairments, swallowing difficulties, and ultimately, a shortened lifespan. Currently, there are no approved treatments for SCA.

Troriluzole is an experimental drug that modulates the glutamate neurotransmitter, the most abundant excitatory messenger in humans. By enhancing the uptake of glutamate from the synapse, it helps lower the overall levels of the neurotransmitter in the synaptic space, preventing neuronal over-excitation and addressing a key mechanism underlying SCA.

Despite its promising mechanism of action, troriluzole's development has encountered several challenges. In August 2023, the FDA declined to review Biohaven’s NDA for troriluzole, citing a failed primary endpoint in the supporting study. The Phase III trial failure was announced in May 2022. Moreover, troriluzole experienced setbacks in other conditions. In January 2021, it failed to produce significant results in an Alzheimer’s disease trial, and nearly a year earlier, it did not meet the primary endpoint in a Phase III trial for generalized anxiety disorder.

Nonetheless, William Blair analyst Myles Minter remains optimistic about troriluzole’s future prospects. Minter noted that the consistent signals of benefit in a population with extremely limited treatment options are encouraging. The firm anticipates that the FDA will convene an advisory committee meeting to discuss the discrepancies between the recent positive data and the initial failed Phase III study.