Topline Findings
- FDA Action: PTC Therapeutics received a Complete Response Letter for vatiquinone, which emphsized the need for additional efficacy data before approval.
- Trial Insights: The MOVE‑FA Phase II/III trial showed a significant benefit on the upright stability subscale of Modified Friedreich Ataxia Rating Scale, despite missing the primary endpoint.
- Rare Disease Context: Friedreich’s ataxia affects approximately one in 40,000–50,000 people in the United States and presents ongoing challenges for drug development in rare diseases.
The FDA has issued a complete response letter (CRL) to PTC Therapeutics for its New Drug Application (NDA) seeking approval of vatiquinone for the treatment of children and adults with Friedreich’s ataxia (FA). According to the company, the application did not provide sufficient evidence of efficacy and the agency indicated that an additional, well-controlled study would be required to support a future resubmission.1
How Does the FDA’s Decision Impact PTC’s Vatiquinone Program?
"We are of course disappointed by the FDA's decision to not approve vatiquinone," said Matthew B. Klein, MD, CEO, PTC Therapeutics, in a press release.
MOVE-FA Trial Design and Endpoints
- In February, PTC submitted the NDA based on data from the randomized, parallel-arm, double-blind, placebo-controlled, Phase II/III MOVE-FA trial (NCT04577352).
- The trial evaluated the efficacy and safety of vatiquinone in 146 patients with FA.
- The trial began with a 72-week randomized, double-blind, placebo-controlled phase in which patients were randomly assigned based on their baseline Modified Friedreich Ataxia Rating Scale (mFARS) score (<40 or ≥40), age of disease onset (<14 or ≥14 years), and their age at screening (≤21 or >21 years).
- From there, patients were randomly assigned to receive either vatiquinone or placebo and then moved into a 24-week open-label extension phase, in which all patients received vatiquinone.
- The primary endpoint of the trial was change from baseline in mFARS score at week 72.
- Key secondary endpoints included change from baseline in Friedreich Ataxia Rating Scale Activities of Daily Living score at week 72, change in baseline from 1-minute walk test (1MWT) at week 72, and the number of falls through week 72.2
- Results showed that while the study failed to meet its primary endpoint, a statistically significant benefit was observed on the pre-specified upright stability subscale of mFARS (p = 0.021).
- Improvements in upright stability were also reflected in positive trends on the 1MWT and the functional component of the Modified Fatigue Rating Scale, indicating a consistent signal of functional benefit, according to the trial investigators.3
Regulatory Context and FDA Scrutiny
The CRL comes amid growing scrutiny of the FDA’s review process and the challenges facing new drug candidates. In July, the agency issued a CRL to Replimune regarding RP1, an advanced melanoma treatment. The company stated that the CRL came as a shock, citing that all concerns raised in the CRL were not brought to its attention during mid- and late-cycle reviews.
Earlier in the same month, Capricor Therapeutics reported a similar issue with a CRL for an investigational Duchenne muscular dystrophy therapy. According to the company, issues with the chemistry, manufacturing, and controls portion of the application cited in the CRL were addressed prior to submitting an NDA.4
FA Overview
- According to Rare Disease Advisor, the prevalence of FA in the United States is approximately one in every 40,000 to 50,000 people.
- Globally, the prevalence is one out of every 22,000 to 50,000 people.
- While a rare disease, FA represented 50% of all cases of inherited ataxias.
- FA is more common in people with European ancestry. It is equally common in men and women.
- The age of onset for FA is typically between early childhood and early adulthood prior to 25 years of age.5
"We believe the data collected to date demonstrate that vatiquinone could provide a safe and effective therapy for both children and adults living with Friedreich's ataxia,” continued Klein, in the press release. “We plan to meet with the FDA to discuss potential steps to address the issues raised in the CRL."
References
- PTC Therapeutics Receives Complete Response Letter for Vatiquinone NDA. PR Newswire. August 19, 2025. Accessed August 20, 2025. https://www.prnewswire.com/news-releases/ptc-therapeutics-receives-complete-response-letter-for-vatiquinone-nda-302533332.html
- A Study to Assess the Efficacy and Safety of Vatiquinone for the Treatment of Participants With Friedreich Ataxia (MOVE-FA). Clinicaltrials.gov. Accessed August 20, 2025. https://clinicaltrials.gov/study/NCT04577352?term=MOVE-FA%20&rank=2
- PTC Therapeutics Announces FDA Acceptance and Priority Review for Vatiquinone NDA for the Treatment of Children and Adults with Friedreich's Ataxia. PTC. February 19, 2025. Accessed August 20, 2025. https://ir.ptcbio.com/news-releases/news-release-details/ptc-therapeutics-announces-fda-acceptance-and-priority-review-0
- Vinay Prasad’s FDA Departure Follows Controversy Over Drug Rejections. PharmExec. July 30, 2025. Accessed August 20, 2025. https://www.pharmexec.com/view/vinay-prasad-fda-departure-controversy-drug-rejections
- Friedreich Ataxia (FA). Rare Disease Advisor. Accessed August 20, 2025. https://www.rarediseaseadvisor.com/disease-info-pages/friedreich-ataxia-epidemiology/#:~:text=Friedreich%20ataxia%20occurs%20at%20a,every%2022%2C000%20to%2050%2C000%20people.&text=The%20carrier%20frequency%20for%20abnormal,60%20to%201%20in%20100.&text=The%20prevalence%20of%20FA%20in,every%2040%2C000%20to%2050%2C000%20people.
