Biohaven Ltd. (NYSE:BHVN) (Biohaven or the Company), today announced positive topline results from pivotal Study BHV4157-206-RWE (NCT06529146) demonstrating the efficacy of troriluzole on the mean change from baseline in the f-SARA after 3 years of treatment. The study achieved the primary endpoint and showed statistically significant improvements on the f-SARA at years 1 and 2 (Figure 1). SCA is a rare, progressively debilitating neurodegenerative disease that affects approximately 15,000 people in the United States and 24,000 in Europe and the United Kingdom. There are no FDA approved treatments for SCA.

Collectively, data across multiple analyses demonstrate a robust and clinically meaningful slowing of disease progression in SCA patients. These treatment benefits translate into a 50-70% slower rate of decline compared to untreated patients, representing 1.5-2.2 years delay in disease progression over the 3-year study period. Additionally, in a responder sensitivity analysis, disease progression when defined by a 2 point or greater worsening on the f-SARA at 3 years showed an odds ratio (OR) of 4.1 (95% CI: 2.1, 8.1) for the untreated external control arm versus troriluzole treated subjects (p < 0.0001; pooled analysis).

Dr. Susan Perlman, Director of Ataxia Clinic and Neurogenetics Clinical Trials at the David Geffen School of Medicine at UCLA stated, "SCA is a debilitating, relentlessly progressive disease that destroys quality of life, leaving patients unable to care for themselves, walk, or speak. 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."

Study BHV4157-206-RWE was designed, in discussion with the US Food and Drug Administration (FDA), to assess the effectiveness of troriluzole in SCA after 3 years of treatment as measured by the change from baseline in the f-SARA. The study utilized Phase 3 data and an external control of matched, untreated SCA subjects from the US Clinical Research Consortium for the Study of Cerebellar Ataxia (CRC-SCA) in accordance with FDA's Guidance on Real-World Evidence (RWE) of effectiveness. All endpoints were prespecified, and both the study protocol and statistical analysis plan were submitted to, and reviewed by, FDA prior to topline data analysis. The new analysis doubled the previously available 3 year data with 63 subjects now completing 3 years of treatment with troriluzole and matched to the external control arm. Propensity Score Matching (PSM) was used to ensure that untreated patients from the CRC-SCA study were rigorously matched to treated patients from Study BHV4157-206 on baseline characteristics. The primary objective was to examine the treatment effects of troriluzole for up to 3 years, by comparing data on the f-SARA from patients treated with troriluzole in Study BHV4157-206 to untreated patients from the natural history study. Troriluzole-treated patients demonstrated statistically significant and sustained benefits at years 1, 2 and 3 on the f-SARA compared to a rigorously matched natural history control.

Additionally, prespecified analyses in the protocol employed a separate, independent natural history control from the European SCA natural history study (EUROSCA) for global regulatory purposes. Results using the EUROSCA patients, in addition to a pooled analysis using both CRC-SCA and EUROSCA patients, as the external controls were also statistically significant and consistent with the primary efficacy analysis at all timepoints (see Figure 2 and Figure 3). The addition of EUROSCA data increased the external control sample size and added to the robustness of the statistically significant treatment differences at years 1, 2, and 3, favoring troriluzole.

Jeremy Schmahmann, M.D., Professor of Neurology at Harvard Medical School and Founding Director of the Ataxia Center at Massachusetts General Hospital commented, "The stabilization of SCA symptoms as reflected by the topline data at 3 years along with the previously reported reductions in falls show the therapeutic potential of troriluzole. I cannot underscore enough the impact of a potential treatment that can slow SCA disease progression and the effect on patients and caregivers who have helplessly watched generations of family members deteriorate and die from SCA. These new data provide support for troriluzole as a safe and effective once daily treatment for patients with SCA."

Spinocerebellar ataxia is a group of dominantly inherited neurodegenerative disorders characterized by progressive loss of voluntary motor control and atrophy of the cerebellum, brainstem and spinal cord. Patients experience significant morbidity, including progression to a wheelchair, impaired gait leading to falls, inability to communicate due to speech impairment, difficulty swallowing, and premature death. While signs and symptoms can appear anytime from childhood to late adulthood, SCA typically presents in early adulthood and progresses over a number of years. Currently, there are no FDA-approved treatments and no cure for SCA.

Vlad Coric, M.D., Chief Executive Officer and Chairman of Biohaven stated, "Advancing new therapies for patients with rare diseases is often a multiyear process of collaboration across academic, patient advocacy, regulatory and industry partners. The Biohaven team has always been committed to rigorously following the science in this area, and through our partnership with the National Ataxia Foundation and collaboration with leading SCA experts across the globe, our SCA development program has provided the first evidence of a clinically meaningful treatment benefit as well as slowing disease progression in SCA patients. We were excited to receive the positive topline results from Study BHV4157-206-RWE, which was designed with FDA input and pursuant to the principles outlined in the FDA's guidance for the use of real-world evidence. The need for treatments for this deadly neurodegenerative disease is urgent. As a company, we remain committed to developing novel therapies for patients living with rare disorders with no approved therapies, like SCA. We look forward to interacting with regulatory agencies to bring troriluzole to patients with SCA."

Andrew Rosen, Chief Executive Officer of the National Ataxia Foundation (NAF), shared, "Biohaven was the first company to join NAF's Drug Development Collaborative (DDC), a group of pharmaceutical companies dedicated to bringing together advocates, clinicians, regulatory agencies, and the patient community to advance research and facilitate the development of therapies for ataxia. Today's topline results are the culmination of years dedicated to studying troriluzole as a treatment for SCA. Patients and families have been waiting for decades for a treatment that could slow disease progression in this devastating and relentlessly progressive disorder".

Based upon the topline data from Study BHV4157-206-RWE, and previous safety and efficacy data from the troriluzole development program in SCA, Biohaven plans to submit a New Drug Application (NDA) to the FDA in Q4 2024. The troriluzole development program has generated the largest clinical trial dataset in SCA and now has follow-up in some patients treated with troriluzole for over 5 years. Biohaven has previously received both Fast-Track and Orphan drug designation (ODD) from the FDA, and ODD from the European Medicines Agency, for troriluzole in SCA. An NDA with ODD is eligible for priority FDA review. Biohaven will be prepared to commercialize SCA in the US in 2025, if ultimately approved, based on potential priority review timelines.