Biohaven enrolls first patient in phase 3 Spinocerebellar Ataxia clinical trial of Troriluzole

Biohaven Pharmaceutical Holding Company, a clinical-stage biopharmaceutical company with a portfolio of innovative, late-stage product candidates targeting neurological and neuropsychiatric diseases, has enrolled the first patient in a Phase 3 clinical trial assessing the efficacy and safety of troriluzole in Spinocerebellar Ataxia (SCA).

Hereditary Spinocerebellar Ataxias are rare, potentially fatal neurodegenerative disorders affecting the cerebellum. They are characterized clinically by progressive ataxia symptoms, including difficulties with balance, speech, and coordination, and are attributed to various autosomal dominant genetic mutations. Currently, there are no FDA-approved treatments and there is no cure for SCA.

Melissa Wolfe Beiner, M.D., Director of Research and Development and Medical Lead for the Ataxia development program at Biohaven commented, “Biohaven has worked closely with leading academic and clinical centers to advance this Phase 3 trial of troriluzole in this area of high unmet need.”  Dr. Wolfe Beiner added, “Based on learnings from our previous Phase 2b/3 clinical trial, we have enriched this trial with specific genotypes, extended the treatment period of this trial to one year, implemented the use of a modified SARA scale and increased the dose of troriluzole to 200 mg. We believe that these changes may improve the ability of the trial to more accurately evaluate troriluzole’s benefit in slowing disease progression in patients with SCA.”

Biohaven expects to enroll approximately 230 patients in this randomized, double-blind, placebo-controlled trial across approximately 22 sites in the United States. Researchers will evaluate the efficacy and safety of troriluzole over 48 weeks in patients with a diagnosis of SCA Types 1, 2, 3, 6, 7, 8, and 10. The primary outcome measure is the change in a patient’s score on the Modified Functional Scale for the Assessment and Rating of Ataxia, a scale designed to assess the severity of symptoms in patients with SCA. Additional details about the trial [NCT03701399] can be found at

Jeremy Schmahmann, M.D., Professor of Neurology at Harvard Medical School and Founding Director of the Ataxia Unit at Massachusetts General Hospital (MGH) added, “We are thrilled to partner with Biohaven and colleagues around the country on this exciting project. We are hopeful that this trial will provide the first convincing evidence of a medication with potential to improve the lives of our patients with SCA.”

Expanded Analysis from SCA Clinical Trial BHV4157-201 and a Matched Natural History Cohort

Biohaven also announced results today of a post-hoc analysis of patients enrolled in the short-term randomization and long-term extension phase of Study BHV4157-201 [NCT02960893], an initial Phase 2b/3 randomized controlled trial of troriluzole in patients with SCA, compared to patients selected from a natural history cohort of SCA patients who were matched on multiple eligibility criteria.

The primary efficacy endpoint for this analysis was the change from baseline in the Scale for the Assessment and Rating of Ataxia (SARA) total score after 48 weeks of follow up. Patients from the natural history cohort were matched to patients from the BHV4157-201 trial on SCA Genotype (SCA1, SCA2, SCA3, SCA6), age at baseline (18 to 75 years of age), gender, SARA Score at baseline (≥ 8 and ≤ 30), and initial score on gait item of the SARA ≥ 2.

Based on analysis of covariance (ANCOVA) least square mean changes after one year were -0.34 points (representing numerical improvement with a 95% confidence interval of -0.94 to 0.26) for 81 troriluzole-treated patients versus +1.07 points (representing numerical decline with a 95% confidence interval of 0.56 to 1.58) for 112 natural history cohort patients (increasing score indicates worsening disease status). The LS Mean difference between cohorts was -1.41 points (95% confidence interval of -2.22 to -0.60) suggesting therapeutic benefits of troriluzole (p=0.0007).

The natural history cohort was derived from a prospective study, conducted by the Clinical Research Consortium for Spinocerebellar Ataxias (Ashizawa, et al. 2013) and recruited from 12 ataxia clinics throughout the United States. Patients in Study BHV4157-201 were treated with 140 mg of troriluzole administered daily for one year.

Gil L’Italien, Ph.D., Head of Global Health Economics and Outcomes Research at Biohaven stated, “The findings from the post-hoc extension phase analysis of troriluzole compared to  matched untreated patients from the natural history cohort are encouraging and provide further support for the potential long-term therapeutic benefit of troriluzole in patients with SCA. We are thrilled to have now enrolled the first patient in the Phase 3 study, which will more fully test the therapeutic potential of troriluzole in treating SCA over the course of one year.”

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