Biohaven Withdraws Marketing Authorization Application for Dazluma, a Treatment for Spinocerebellar Ataxia, in Europe
Biohaven has withdrawn its marketing authorization application for Dazluma (active ingredient: troriluzole), a treatment for Spinocerebellar Ataxia Type 3 (SCA3), from the European Medicines Agency (EMA). This decision, made on March 24, 2025, followed the Committee for Medicinal Products for Human Use (CHMP) indicating that it was unlikely to grant New Active Substance (NAS) designation. Dazluma is a prodrug of riluzole, a treatment for Amyotrophic Lateral Sclerosis (ALS). Regulatory authorities determined that there was insufficient data to demonstrate a significant chemical and clinical difference compared to existing drugs. This has led to a complete revision of Biohaven's European market entry strategy, which aimed to secure regulatory benefits and market exclusivity.
The European regulatory authorities raised significant concerns not only about the chemical uniqueness of the substance but also about the efficacy of Dazluma in treating SCA. Biohaven claimed that, based on the results of a Phase 3 trial (BHV4157-206-RWE) using an external natural history cohort as a comparator, Dazluma slowed disease progression by 50% to 70%. However, the regulatory agency deemed this claim unreliable. The use of Real-World Evidence (RWE) instead of a standard randomized controlled trial raised concerns about potential confounding variables and selection bias. This represents a stricter regulatory approach than the industry had anticipated for flexible regulations in rare neurodegenerative diseases.
The withdrawal in Europe has had a cascading impact on Biohaven's global commercialization strategy, including its plans for the US market. Biohaven had submitted a marketing authorization application for Dazluma (US brand name: Vyglxia) to the US FDA, but in November 2025, it received a Complete Response Letter (CRL) due to the same statistical flaws and lack of efficacy data. With approval denied in both Europe and the US, the company's pipeline value has been significantly diminished. Biohaven will now need to redesign and conduct additional large-scale clinical trials with a reliable comparator or supplement the existing data with post-hoc analyses, incurring substantial additional costs to re-secure approval.
SCA is a rare disease with a high unmet medical need, as there are currently no effective disease-modifying therapies available worldwide. The global market size is estimated at $373.24 million in 2024 and is projected to grow at a CAGR of 7.4% to $767.2 million by 2033. While the launch of Dazluma is delayed, competitors such as Vico Therapeutics (VO659) and Arrowhead and Sarepta (ARO-ATXN2), which are jointly developing new drugs using gene silencing technology, are accelerating their development. Biohaven has missed the opportunity to be the first to market, and its position in the market may be further weakened depending on the clinical progress of its competitors.
The withdrawal of Dazluma's marketing authorization application in Europe and the receipt of a Complete Response Letter (CRL) in the US serve as a significant regulatory precedent, raising concerns about the approval of treatments for rare diseases based solely on Real-World Evidence (RWE) and natural history data. From a research perspective, the value and rigor of randomized controlled trial designs are re-emphasized in the SCA market, which is projected to grow to $767.2 million by 2033. From an investor perspective, Biohaven faces short-term declines in corporate value due to increased clinical costs and delays in European and US launches, as well as the loss of the opportunity to secure market exclusivity. In the medium to long term, competitors such as Vico Therapeutics' ASO therapy, VO659, and Arrowhead's ARO-ATXN2, with their next-generation mechanisms of gene therapy, are poised to accelerate their pipeline development and rapidly gain market share, creating a turning point in the market.
Source: EMA (ema)