PTC Therapeutics has long been trying to workshop its vatiquinone into a marketable treatment for Friedreich's ataxia (FA) after a phase 3 fail in 2023. Despite its efforts, the FDA has snubbed the drug with a complete response letter asking for a new study.
The agency explained that vatiquinone did not show “substantial evidence of efficacy” and that a new, well-controlled study would be needed to support a resubmission, according to PTC.
"We are of course disappointed by the FDA's decision to not approve vatiquinone," CEO Matthew Klein, M.D., said in the company's press release. "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.”
“We plan to meet with the FDA to discuss potential steps to address the issues raised in the CRL,” Klein added.
The rejection quashes the glimmer of hope the company saw after a March 2024 type C meeting with the FDA, where PTC made its case for its phase 3 Move-FA study despite missing its primary endpoint.
Move-FA didn’t show a statistically significant change from baseline in the overall modified Friedreich Ataxia Rating Scale (mFARS) score of evaluated patients, but PTC held onto a statistically significant effect in another pre-specified endpoint, the mFARS upright stability subscale. According to the biotech, this measure is “now understood to be the most sensitive and relevant” for the enrolled population.
“We demonstrated significant benefits on the only thing you possibly could show significant benefit on disease progression, and that's the upright stability scale,” Klein said in an investor briefing after last year's FDA meeting. According to the exec, there has been an advancement in the understanding of FA and the importance of the upright stability on an ambulant adolescent population since Move-FA began.
Vatiquinone later hit pre-specified endpoints in two separate long-term extension studies. The company used all three studies to bulk up its FDA submission in December.
After the initial Move-FA miss in 2023, PTC cut staff and conducted a pipeline prioritization. Shortly after the FA fail, vatiquinone didn’t move the needle in a separate indication for a rare seizure disorder. That setback prompted the company to scrap its vatiquinone efforts in the disease entirely, focusing solely on FA.
If it were to gain the FDA’s good graces, PTC's oral small molecule drug would compete on the 25,000 global patient-wide FA market with Biogen’s Skyclarys, the first drug approved for the hereditary neurological disorder. Biogen got its hands on the rare disease drug from its Reata Pharmaceuticals buyout and has since ushered it across the regulatory finish line in Europe. In its studies, Skyclarys won over placebo on “each component” on the mFARS assessment, according to Biogen.
PTC hoped to have an edge over Skyclarys with a broader label in the rare genetic disorder. Biogen’s offering is only approved to treat patients aged 16 and older, while PTC studied its prospect in children as well.
FA is an autosomal recessive neurodegenerative disease that mainly impacts the nervous system. Patients with the disorder have a shorter life span expectancy than the average population.