Disc’s once-spurned rare disease drug to get a second chance at approval

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A rare disease drug previously spurned by the Food and Drug Administration will get another shot at approval after positive Phase 3 results that sent shares of its developer, Disc Medicine, soaring by more than 35%. 

Disc said Monday that the treatment, bitopertin, met all of its main and secondary objectives in a Phase 3 trial in erythropoietic porphyria, an uncommon disease causing hypersensitivity to light. The findings position Disc to resubmit an approval application to the Food and Drug Administration by the end of the year and possibly launch the therapy in 2027. 

“Today represents a potential breakthrough in the science and treatment of EPP,” said Disc’s top executive John Quisel, in a statement. “We look forward to engaging with regulators with the goal of bringing an important, innovative medicine to this community as efficiently as possible.”

The announcement gives Disc, which went public via a reverse merger four years ago, another opportunity to win its first drug approval.  

Disc licensed bitopertin from Roche. The Swiss pharmaceutical giant had unsuccessfully tested the therapy against schizophrenia, but Disc chose to reposition it as a potential treatment for erythropoietic porphyria, also referred to as EPP.

EPP causes a substance called protoporphyrin IX, or PPIX, to abnormally build up in the blood, leading to painful reactions to bright light. Only one marketed therapy is available, an implant called Scenesse that increases production of melanin in the skin. Another prospective treatment owned by LEO Pharma, dersimelagon, could be approved by regulators next year.

Bitopertin works differently than both of those treatments. It’s an oral medication that blocks a target on developing red blood cells known as “GlyT1” which, in turn, is meant to slow the accumulation of toxic PPIX in the bloodstream.

The medication showed the ability in Phase 2 trials to improve signs of disease severity and drop levels of PPIX. Afterwards, it became one of the first drugs to receive a “national priority” review voucher from the FDA, a new kind of fast pass created under former FDA commissioner Marty Makary. 

But a clearance has proven an uphill battle for Disc. A report from Stat News indicated former Makary deputy Vinay Prasad was skeptical of Disc’s results. The FDA formally rejected an accelerated approval request in February, stating in a complete response letter that Disc’s trials didn’t clearly show a link between PPIX reductions and more tolerance to sunlight. The letter did, however, state that Disc could achieve a traditional clearance should bitopertin succeed in a Phase 3 trial. 

In the meantime, FDA leadership has since been upended. Newer leaders have taken a friendlier stance towards rare disease medicines, reversing course on multiple rejections and, more recently, revealing plans to enact a more flexible review framework.

Disc could capitalize on those changes. The results issued Monday showed its therapy drove down PPIX counts by about 46% after six months, versus just over a 4% reduction for placebo recipients. Treatment was also associated with a 12.2-hour increase, relative to a placebo, in pain-free time in light during the sixth month. Other measures of light tolerance, such as a steep reduction in the painful skin reactions patients experience, were also observed. 

The drug was “well-tolerated,” according to Disc. Dizziness was the most common treatment-related side effect. 

The findings are “compelling” and “substantially” address the concerns raised by the FDA, wrote Leerink Partners analyst Thomas Smith. 

Jefferies analyst Roger Song added in a separate note that the data are “strongly supportive of a potential regular or full approval with a best-in-class profile.” Song expects broad adoption and a $1 billion to $2 billion market opportunity.