Biohaven Sets Stage for Comeback With Pivotal Study Results in Spinocerebellar Ataxia

The FDA previously refused to review Biohaven’s candidate in the indication due to a failed late-stage trial. However, the company is now planning to file an NDA in the fourth quarter of 2024.

Biohaven on Monday unveiled topline pivotal data for its drug candidate troriluzole, touting significant symptomatic and functional improvements in patients with spinocerebellar ataxia.

Troriluzole treatment led to “robust and clinically meaningful slowing of disease progression” with the investigational treatment slowing down patients’ rate of decline by 50% to 70% versus untreated comparators, according to the company, while delaying disease progression by 1.5 years to 2.2 years over the study’s three-year duration.

Using the modified functional Scale for the Assessment and Rating of Ataxia (f-SARA) tool, which classifies disease progression as at least a two-point worsening in score, Biohaven found that untreated patients were more than four times more likely to progress, compared with patients on troriluzole.

CEO Vlad Coric in a statement said that Biohaven’s spinocerebellar ataxia (SCA) program, which includes Monday’s pivotal study, “has provided the first evidence of a clinically meaningful treatment benefit as well as slowing disease progression in SCA patients.”

“The need for treatments for this deadly neurodegenerative disease is urgent,” Coric said. “We look forward to interacting with regulatory agencies to bring troriluzole to patients with SCA.” Biohaven is gearing up for a New Drug Application (NDA) in the fourth quarter of 2024, backed by the results from Monday’s readout, as well as previous efficacy and safety data.

SCA refers to a group of heritable neurodegenerative disorders that typically involve the progressive loss of voluntary control over movement. The disease class also leads to the gradual atrophy of several crucial parts of their nervous system, including cerebellum, brainstem and spinal cord. Patients suffer from compromised motor skills, often leading to falls and other related injuries. SCA can also manifest as speech impairments, difficulties swallowing and, ultimately, premature death. There are currently no approved treatments for SCA.

Biohaven’s troriluzole is an investigational modulator of the glutamate neurotransmitter, which is the most abundant excitatory messenger in humans. By boosting the uptake of glutamate from the synapse, it helps lower the overall levels of the neurotransmitter in the synaptic space, preventing the over-excitation of neurons and addressing a key pathway in SCA.

However, despite a promising mechanism of action, troriluzole’s development has run into several rough patches in recent years. In August 2023, the FDA refused to review Biohaven’s NDA for troriluzole, pointing out that the study used to support the application failed its primary endpoint. The biotech announced the Phase III failure in May 2022.

Troriluzole has also run into difficulties beyond SCA. In January 2021, Biohaven unveiled disappointing Alzheimer’s disease data for the drug candidate, revealing that it had failed to significantly outperform placebo at 48 weeks. Nearly a year earlier, troriluzole failed a Phase III study in generalized anxiety disorder.

Still, William Blair analyst Myles Minter is optimistic about troriluzole’s chances moving forward. Minter in a note to investors said that they are “encouraged by the consistent signals of benefit … in a population with extremely limited treatment options.” The firm expects the FDA to call for an advisory committee meeting to discuss the differences between Monday’s readout and the first failed Phase III study.

https://www.biospace.com/drug-development/biohaven-sets-stage-for-comeback-with-pivotal-study-results-in-spinocerebellar-ataxia