Disc Medicine’s Bitopertin Nails Phase III Endpoints, Eyes FDA Resubmission

Key Points

• Bitopertin met all APOLLO Phase III endpoints in EPP and XLP, reducing metal-free PpIX by 45.8% and increasing monthly pain-free sunlight exposure by 12.2 hours versus placebo.
• The treatment also reduced severe phototoxic reactions by 71% and improved patient-reported quality-of-life measures. No patients discontinued treatment, though dizziness was reported by 50% of bitopertin recipients.
• Disc Medicine plans to resubmit bitopertin’s FDA application by year-end, potentially leading to an FDA decision by mid-2027, while preparing commercial testing and advancing its broader hematology pipeline.

Disc Medicine NASDAQ: IRON said its Phase III APOLLO trial of investigational bitopertin met both co-primary endpoints and all secondary endpoints in patients with erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP), supporting the company’s plan to resubmit a new drug application to the U.S. Food and Drug Administration by the end of the year.

Chief Executive Officer John Quisel said the company anticipates an FDA decision by mid-2027 if the application proceeds on the expected timeline. Bitopertin is an investigational once-daily oral therapy intended to reduce production of protoporphyrin IX, or PpIX, the metabolite that accumulates in EPP and XLP and drives severe light sensitivity and phototoxic reactions.

APOLLO met co-primary endpoints

The randomized, double-blind, placebo-controlled APOLLO study enrolled 183 adults and adolescents age 12 and older with EPP or XLP. Participants received either 60 mg of bitopertin or placebo for six months. The trial exceeded its original enrollment target of 150 patients, with enrollment completed in 10 months.

According to Chief Medical Officer Will Savage, bitopertin reduced whole-blood metal-free PpIX by 45.8% from baseline at month six. The treatment produced a 41.4% greater reduction in PpIX than placebo, with a p-value of less than 0.0001.

The other co-primary endpoint measured average total monthly time spent in sunlight without pain between 10 a.m. and 6 p.m. during the sixth month of treatment. Bitopertin improved time in light without pain by 12.2 hours relative to placebo, with a p-value of 0.001.

“This is the first time a potential treatment for EPP has shown robust evidence of whole blood PpIX reduction alongside unequivocal improvement in time in light and substantial reduction in phototoxic reactions,” Savage said.

Secondary measures showed fewer pain reactions

Bitopertin reduced the incidence rate of severe, painful phototoxic reactions by 71% compared with placebo, with a p-value below 0.0001. Over the six-month treatment period, the company reported 71 phototoxic reactions among bitopertin-treated patients, compared with 231 in the placebo group.

Patients receiving bitopertin also recorded 58 additional cumulative hours in sunlight without pain over six months relative to placebo, according to the company. In an adult-only analysis of sunlight exposure challenges, treatment increased the average daily time to prodromal symptoms by 56 minutes versus placebo at month six, with a p-value of 0.0077.

Disc Medicine also reported statistically significant improvements in patient-reported quality-of-life measures, including patient global impression of change and patient global impression of severity scores. The company said more bitopertin-treated patients characterized their condition as “much better” and their disease severity as “not at all severe” at the end of the study.

Safety profile and regulatory plans

There were no treatment discontinuations in the bitopertin group during APOLLO, Disc Medicine said. Three serious adverse events occurred in the trial—two in the placebo group and one in the bitopertin group—and none was considered treatment-related.

Dizziness was the most frequently reported treatment-emergent adverse event, occurring in 50% of bitopertin patients and 11% of placebo patients. Savage said the events were mild to moderate, generally arose within one day of treatment initiation and were generally transient.

Quisel said bitopertin has been evaluated in more than 4,000 clinical trial participants over its development history. The company also cited results from its ongoing HELIOS long-term extension study, where it said PpIX reductions have persisted for years and time in light has continued to improve beyond six months of treatment.

The company plans to present more detailed APOLLO data at a future medical conference. It is continuing treatment access through the HELIOS open-label extension study and an expanded-access program in the U.S. and selected other countries. Quisel said approximately 150 patients are currently enrolled in HELIOS, while demand in the expanded-access program has been high.

Commercial preparation and broader pipeline

Chief Commercial Officer Pamela Stephenson said Disc Medicine estimates that up to 20,000 people may be living with EPP in the U.S. Based on claims data, the company estimates roughly 14,000 patients age 12 and older have been diagnosed, including approximately 6,000 “engaged” patients with multiple or recent EPP-related claims.

Disc Medicine plans to launch a PpIX testing program in November to provide more accessible testing for EPP and XLP. Stephenson said the company’s commercial teams have been working with healthcare providers to validate patients and increase disease awareness, particularly at leading treatment centers and community accounts.

Beyond bitopertin, Disc Medicine said selcodebart is being evaluated in anemia of myelofibrosis, while DISC-3405 is being evaluated in polycythemia vera and sickle cell disease. The company said both programs produced positive Phase II readouts earlier in 2026 and are expected to enter Phase III studies in 2027.

About Disc Medicine (NASDAQ:IRON)

Disc Medicine, Inc is a clinical-stage biopharmaceutical company focused on developing treatments for serious hematologic diseases. The company's research centers on disorders involving the production of red blood cells, iron metabolism and heme biology, areas that can contribute to anemia and other blood-related complications.

Disc Medicine's lead product candidate is bitopertin, an oral small-molecule therapy designed to modulate glycine transporter 1 and influence heme production. The company is evaluating bitopertin in conditions including erythropoietic protoporphyria, a rare disorder associated with painful light sensitivity, as well as polycythemia vera and other hematologic diseases.

The company is also developing additional therapies intended to regulate iron availability and address anemia associated with chronic or hematologic conditions.

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