Biohaven has been persevering with the development of troriluzole, a drug aimed at treating the rare neurodegenerative disorder spinocerebellar ataxia (SCA), despite a series of clinical trials and regulatory setbacks. This persistence seems poised to pay off as the company approaches a new drug application, leveraging a novel approach using real-world data to satisfy regulatory requirements.
Troriluzole functions as a prodrug that modifies brain chemistry by lowering levels of glutamate, which, while vital for brain function, can exacerbate neurodegeneration when present in excess. Initial attempts to use troriluzole in treating conditions such as anxiety and Alzheimer’s disease were unsuccessful, and the drug is currently being tested for obsessive compulsive disorder in a Phase 3 trial.
SCA encompasses a group of inherited disorders leading to progressive loss of motor control and brain degeneration, specifically in the cerebellum, brainstem, and spinal cord. It presents typically in early adulthood, affecting about 15,000 people in the U.S. and 24,000 in Europe and the U.K. Symptoms include frequent falls, mobility issues necessitating wheelchair use, speech and swallowing difficulties, and premature death.
In 2022, Biohaven’s initial Phase 3 study of troriluzole in SCA yielded disappointing results, failing to demonstrate significant efficacy, which the company attributed to an unexpectedly slow progression of the disease in the placebo group. A subsequent, deeper analysis, however, suggested a potential benefit for patients with type 3 SCA, the most prevalent form among the more than 40 types identified.
Following these initial setbacks, including a refuse-to-file notice from the FDA which stalled a previous application for drug approval, Biohaven redesigned its trial protocol to incorporate real-world evidence. This new study compared treated patients with historical controls from both the U.S. and Europe, using data covering a three-year period. Preliminary results were promising, showing statistically significant and sustained benefits in disease progression across all SCA types over a three-year period, suggesting a 50% to 70% slower decline compared to untreated patients.
These findings have prompted Biohaven to announce plans for a comprehensive FDA approval push for troriluzole as a treatment across all forms of SCA. The company aims to file a new drug application in the latter part of the year. Additionally, a marketing authorization application for the drug is already under review in Europe.
Investor response, as summarized by analysts from William Blair and Leerink Partners, has been mixed but cautiously optimistic. The real-world data approach, strongly encouraged by FDA guidance, has been seen as a positive development, though there remain concerns about the drug’s regulatory risks, highlighted by its earlier Phase 2/3 and Phase 3 failures.
The outcomes from these analyses and the impending advisory committee discussions sought by the FDA are anticipated to critically impact the drug’s regulatory pathway—particularly given its prior setbacks and the new trial design’s departure from more traditional methodologies. Such discussions will likely cover the notably different outcomes between the original Phase 3 study and the subsequent analysis using natural history comparators, as well as potential variances in the standard of care provided over the periods the historical data were collected.
In conclusion, Biohaven’s strategic pivot to utilizing real-world data for troriluzole’s development marks a notable chapter in its journey towards offering a potentially game-changing therapy for individuals with SCA, a group with few existing treatment options. The final verdict from the FDA, however, will depend heavily on forthcoming discussions and analysis of both the new and old datasets, bearing significant implications for the drug’s future and for patients affected by this challenging disorder.
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