FDA rejects PTC request for vatiquinone approval for FA
Regulatory agency cites insufficient evidence of therapy's effectiveness
The U.S. Food and Drug Administration (FDA) has declined to approve the oral therapy vatiquinone for treating children and adults with Friedreich’s ataxia (FA).
In a complete response letter, the regulatory agency said it would not approve vatiquinone at this time because of a lack of adequate data that the treatment is effective, according to a press release from the therapy’s developer PTC Therapeutics. The FDA said PTC would need to run an “additional adequate and well-controlled study” to support a resubmission of its application seeking the therapy’s approval, the release stated.
“We are of course disappointed by the FDA’s decision to not approve vatiquinone,” said Matthew B. Klein, MD, PTC’s CEO.
PTC said it would seek to meet with the FDA to plan out the next steps in vatiquinone’s development.
A genetic disorder, FA is caused by mutations that lead to the dysfunction of nerve and muscle cells. Vatiquinone, previously known as PTC-743, is a small molecule designed to reduce disease progression by dampening brain inflammation. It specifically works to block the activity of a protein called 15-lipoxygenase, which is involved in the regulation of certain inflammation-related pathways. Vatiquinone is designed to be taken by mouth three times daily.
Had the therapy been approved, it would have been the first in the U.S. for young children with FA. The only approved therapy to date, Skyclarys, is indicated for FA patients 16 or older.
MOVE-FA trial data had supported vatiquinone approval request
PTC’s application seeking approval of vatiquinone for FA was based mainly on data from a Phase 2/3 clinical trial called MOVE-FA (NCT04577352). That trial enrolled 146 patients ages 7 and older — most of whom were children. Participants were randomly assigned to take vatiquinone or a placebo for about 1.5 years.
The main goal of MOVE-FA was to see if vatiquinone could slow disease progression among patients, as measured by the standard assessment mFARS, fully, the modified Friedreich Ataxia Rating Scale.
The results showed the trial failed to meet this goal, as mFARS scores were not significantly different between those on the therapy versus the placebo. However, a subscale of the mFARS that’s related to upright stability did show a statistically significant difference favoring vatiquinone over the placebo.
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 [complete response letter].
PTC argued that this subscale was the most sensitive part of the mFARS for the enrolled trial population, and that the scores on it were especially indicative of better function in children.
After MOVE-FA ended, participants had the option to join an extension study in which all were treated with vatiquinone and monitored for long-term outcomes. Long-term data from the extension study indicated that the decline in total mFARS scores was slowed by approximately 50% in patients given vatiquinone when compared with natural history data.
“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,” Klein said. “We plan to meet with the FDA to discuss potential steps to address the issues raised in the CRL [complete response letter].”
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