Disc Medicine has announced a US Food and Drug Administration (FDA) agreement on the regulatory path for its investigational drug bitopertin in treating the rare skin condition erythropoietic protoporphyria (EPP).
Following an end of Phase II meeting, the FDA indicated support for an accelerated approval application based on existing clinical data, with the upcoming Phase III trial serving as a confirmatory study. The agency has agreed with Disc’s proposed trial design and endpoints, including the use of protoporphyrin IX (PPIX) reduction as a surrogate marker.
This potential approval would hinge on bitopertin’s ability to enable pain-free sunlight exposure for patients with EPP and X-linked protoporphyria (XLP). EPP is a genetic disorder that causes a phototoxic heme precursor to build up in the red blood cells. Both conditions are associated with severe burn injuries on the skin after as little as ten minutes of exposure to visible light.
Data from the Phase II trial showed that once-daily doses of bitopertin at 20mg and 60mg were well tolerated over 24 weeks in 22 patients, with no serious adverse events reported. Participants also had the option to continue in an open-label extension of the study for an additional 24 weeks.
Disc plans to launch the Phase III APOLLO trial by mid-2025. The FDA agreed that the trial’s primary endpoint – measuring average monthly time in sunlight without pain during the final month of a six-month treatment – appropriately reflects the drugs’ potential benefit. The agency also approved a 60mg dose of bitopertin and a six-month trial duration, along with secondary outcome measures such as PPIX levels, phototoxic reactions, cumulative pain-free sunlight exposure, and patient global impression of change.
The APOLLO study will include patients aged 12 and older with EPP or XLP and will follow a single, randomised, double-blind, placebo-controlled design. The company expects to finalise details with the FDA and provide an update on the NDA timeline in Q1 2025.
A patient with the rare skin disorder recently highlighted the ethical challenges in EPP trials at the Outsourcing in Clinical Trials (OCT) DACH 2024 conference, in Zurich, Switzerland, between 29 and 30 October. EPP trials have to reckon with the potential for phototoxic burns in participants randomized to control groups, and the risk of a bias in patient selection, as more severely affected patients may hesitate to participate.
In the announcement accompanying the update, Disc’s CEO John Quisel said: “We’re particularly excited by the potential to file under the Accelerated Approval Program based on our existing data and use of PPIX reduction as a surrogate endpoint.”
There is only one approved treatment for the condition: Scenesse (afamelanotide), developed by Australia-based biotech Clinuvel Pharmaceuticals. The drug increases skin pigmentation and has anti-inflammatory properties, offering protection against light-induced skin damage. The results from a pivotal trial (NCT01605136) showed that patients receiving Scenesse could spend an average of 20 minutes in sunlight daily without experiencing pain, compared to those on a placebo.