A phase 3 trial of Disc Medicine’s bitopertin has hit its co-primary and secondary endpoints, positioning the biotech to refile for approval of the once-rejected rare disease drug candidate. Disc shares jumped 55% to $88.37 in premarket trading.
The FDA declined to approve bitopertin in February. Officials knocked back Disc’s request for approval in erythropoietic protoporphyria (EPP), a rare inherited metabolic disorder, over doubts about whether a change in a surrogate endpoint would translate into improved clinical outcomes. Officials noted the lack of a demonstrated link between changes in the biomarker and increased sunlight exposure, which is painful for people with EPP.
Disc’s phase 3 trial provides a clearer link between the biomarker, whole-blood metal-free protoporphyrin IX (PPIX), and exposure to sunlight. Compared to placebo, whole-blood metal-free PPIX fell 41.4% relative to baseline, achieving one of the co-primary endpoints and confirming the drug candidate's effect on the surrogate marker.
In month six, patients on bitopertin spent an average of 12.2 hours a month longer in light without pain than their peers on placebo. The result met the trial’s other co-primary endpoint and strengthened the link between reduced PPIX and increased ability to tolerate sunlight. BMO Capital Markets analysts called the data “overwhelmingly positive” in a note to investors.
“These newly released data clearly demonstrate the overwhelming efficacy of the asset in patients living with EPP,” BMO analysts said. “Bitopertin’s impact on whole blood metal-free PPIX and ability to meaningfully increase sunlight tolerance point to a new standard of care in EPP.”
Existing treatment options include Clinuvel Pharmaceuticals’ Scenesse. A “pretty small number” of EPP patients take Scenesse, Disc CEO John Quisel, Ph.D., said at a Morgan Stanley event last month. Disc aims to reach more patients, starting with the 600 or so people treated at the top 10 to 15 centers, Quisel said.
Disc needs to reach patients beyond those 600 individuals to hit its peak sales target, the CEO added. The consensus peak sales estimate, adjusted for the probability of approval, is $1 billion, BMO analysts said. The BMO team has higher hopes than its peers, putting peak sales at $1.2 billion. Disc plans to refile for FDA approval by the end of the year and anticipates an FDA decision by mid-2027.
The biotech’s pursuit of FDA approval and blockbuster sales is supported by positive results across the trial’s secondary endpoints. Disc reported a reduced rate of phototoxic reactions, as well as an increase in total time in light without pain. The trial also linked the asset to an increase in the time between sunlight exposure and the onset of early symptoms.
Disc reported significant gains on two exploratory measures of quality of life. The drug candidate was generally well tolerated, with no treatment-emergent adverse events (TEAEs) above grade 3. The most commonly reported TEAE in the bitopertin group was dizziness, which affected half of patients but was mild or moderate and generally transient.
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