FDA denies accelerated approval of bitopertin, awaits trial results
Positive data from ongoing Phase 3 trial could support traditional approval
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The U.S. Food and Drug Administration (FDA) has rejected an application from Disc Medicine seeking accelerated approval of its experimental oral therapy bitopertin as a treatment for erythropoietic protoporphyria (EPP).
According to Disc, the FDA said available clinical data aren’t sufficient to conclude that bitopertin is likely to provide clinical benefit for EPP patients. However, the agency indicated that data from an ongoing Phase 3 clinical trial, APOLLO (NCT06910358), would be sufficient to support traditional approval if the results are positive. The APOLLO study is recruiting patients 12 and older with EPP or X-linked protoporphyria, another type of porphyria, at sites across Europe, the U.S., Australia, and Canada.
“We are committed to delivering bitopertin to patients, knowing how critical this potentially disease-modifying therapy is to the EPP community,” John Quisel, PhD, Disc’s president and CEO, said in a company press release.
The FDA’s rejection “will delay the potential approval of bitopertin, but we have confidence in the ongoing APOLLO trial, for which we are seeing incredible enthusiasm from the EPP community,” Quisel said. “Confidence in our product and program guides our approach, and we will continue working closely with the FDA to support their review.”
Where the data fell short
EPP is a genetic disorder in which porphyria symptoms, such as abnormal sensitivity to sunlight, are driven by the toxic buildup of a molecule called protoporphyrin IX (PPIX) in the body’s tissues. Bitopertin is designed to reduce the buildup of PPIX and ease EPP symptoms.
The FDA’s accelerated approval program allows medications to be conditionally authorized based on early clinical evidence that a treatment is likely to benefit patients. Disc sought accelerated approval for bitopertin based on data indicating that the treatment can reduce PPIX buildup as designed. The company’s application was based mainly on data from two Phase 2 trials, BEACON (ACTRN12622000799752) and AURORA (NCT05308472).
For the FDA to grant accelerated approval, two specific conditions must be met. First, the experimental treatment must be shown to affect a disease-related biological marker. In its rejection, the FDA agreed that this condition had been met; data from BEACON and AURORA showed the therapy reduced PPIX levels, with sustained reductions over long-term treatment in an extension study.
The second condition is that the magnitude of the effect on the disease biomarker must be reasonably likely to predict actual clinical improvement in patients. This is where the FDA said there isn’t currently enough evidence. Although Phase 2 data indicated that bitopertin allowed EPP patients to spend more time in the sun without pain, the FDA said there wasn’t a clear connection between changes in PPIX levels and patient-reported changes in symptom severity. As such, the FDA said the available data aren’t enough to conclude that reductions in PPIX will actually translate into clinical improvements for patients.
Still, the FDA said the ongoing Phase 3 APOLLO study could support a traditional approval (that is, a regular non-conditional approval where a medication has been proven to be reasonably safe and clinically effective). The study is comparing six months of treatment with bitopertin against a placebo, with the main goals of evaluating the therapy’s safety, its effect on PPIX levels, and the amount of pain-free time patients can spend in the sun.
Disc said it expects the APOLLO study to finish recruitment within the next month or two, and top-line results should be available before the end of the year.
“While our efforts at utilizing expedited pathways to get bitopertin to patients quickly have not come to fruition, we are continuing to pursue all avenues in support of FDA approval,” Quisel said.
Disc plans to submit a response to the FDA after the APOLLO data is available, with a potential updated FDA decision expected by mid-2027.
