Disc Medicine’s Bitopertin Meets Main Goals in Late-Stage Trial for EPP

Rare Daily Staff

Disc Medicine said its experimental drug bitopertin met all primary and secondary goals in a pivotal phase 3 trial involving people with erythropoietic protoporphyria, a rare inherited disease that can make exposure to sunlight intensely painful.

The company said patients who received the once-daily pill spent more time in light without pain, experienced fewer light-triggered reactions and had lower levels of the toxic substance that causes the disease than those who received a placebo.

Disc plans to resubmit its application for U.S. Food and Drug Administration approval by the end of 2026 and anticipates a decision by mid-2027.

Erythropoietic protoporphyria (EPP) disrupts the body’s production of heme, a component of the protein that carries oxygen in red blood cells. The disruption causes protoporphyrin IX, known as PPIX, to accumulate. This light-sensitive substance can trigger severe pain, burning and swelling when patients are exposed to sunlight. It can also accumulate in the liver and cause damage. Patients often limit outdoor activities and rely on protective clothing and other measures to avoid light, with substantial consequences for daily life.

Bitopertin is an oral drug that blocks glycine transporter 1 (GlyT1), which supplies developing red blood cells with glycine, a building block needed to make heme. The drug is designed to alter heme production and reduce the buildup of PPIX. Disc plans to develop bitopertin as a potential treatment for a range of blood disorders, including erythropoietic porphyrias, for which the company says it could become the first disease-modifying therapy.

The APOLLO trial enrolled 183 adults and adolescents ages 12 and older with EPP or the related condition X-linked protoporphyria. Participants in the United States, Canada, Europe and Australia were randomly assigned to receive either 60 milligrams of bitopertin or a placebo daily for six months. Neither participants nor investigators knew which treatment patients received.

The study had two primary goals: lowering whole-blood PPIX levels and increasing time spent in light without pain.

Disc reported a 41.4 percent reduction in PPIX relative to placebo. During the sixth month of treatment, patients taking bitopertin also averaged 12.2 additional hours in light without pain compared with those taking placebo. Both findings were statistically significant.

The drug also met all secondary goals, including reducing the rate of painful light-triggered reactions and increasing cumulative time in light without pain over the six-month treatment period. An adult-only measure showed improvement in the time patients could spend in sunlight before developing early warning symptoms.

Patients also reported improvements in their overall condition and perceived disease severity on exploratory measures.

Dizziness was the most commonly reported treatment-emergent adverse event among patients receiving bitopertin, occurring in 50 percent of those patients. Disc said the episodes were mild or moderate and generally temporary. The company reported no new safety signals.

“These results are compelling evidence of the clinical benefit of a mechanism aimed at reducing the production of PPIX, the fundamental cause of disease,” said Will Savage, Disc’s chief medical officer.