Disc Reports Positive Initial Data from Phase 2 Trial of Bitopertin Rare Blood disorders

Rare Daily Staff

Disc Medicine presented positive preliminary findings from its ongoing, phase 2 open-label BEACON trial evaluating bitopertin in patients with the rare blood disorders erythropoietic protoporphyria and X-linked protoporphyria at the European Hematology Association 2023 Congress in Frankfurt, Germany.

The initial trial data demonstrated dose-dependent reductions of protoporphyrin IX (PPIX), significant increases in reported sunlight tolerance, and improvements in measures of patient quality of life. Bitopertin was well-tolerated, with no meaningful changes in hemoglobin observed.

Erythropoietic protoporphyria (EPP) and X-linked Protoporphyria (XLP) are rare, debilitating and potentially life-threatening diseases caused by mutations that affect heme biosynthesis, resulting in the accumulation of a toxic, photoactive intermediate called protoporphyrin IX (PPIX). This causes severe reactions when patients are exposed to sunlight, characterized by excruciating pain, edema, burning sensations and potential blistering and disfigurement. PPIX also accumulates in the hepatobiliary system and can result in complications including gallstones, cholestasis, and liver damage in 20 to 30 percent of patients and in extreme cases liver failure.

The current standard of care involves extreme measures to avoid sunlight, including restricting outdoor activities to nighttime, use of protective clothing and opaque shields, and pain management. This has a significant impact on the psychosocial development, quality of life, and daily activities of patients, particularly in young children and families. There is currently no cure for EPP and only one FDA-approved therapy, a surgically implanted synthetic hormone designed to stimulate melanin production called Scenesse.

“Over the next 12 months, we plan to build on this momentum with a series of additional clinical read-outs across our portfolio,” said John Quisel, CEO and president of Disc Medicine.

The BEACON trial is a randomized, open-label, parallel-arm trial enrolling up to 22 patients with EPP or XLP at trial sites in Australia. This trial was designed to assess changes in levels of PPIX, as well as measures of photosensitivity, quality of life, and safety and tolerability. Subjects are randomized to receive either 20 mg or 60 mg of bitopertin once-daily for 24 weeks, after which patients have the option of continuing in an open-label extension of the trial for up to an additional 24 weeks. The trial is ongoing and these data reflect initial data from 15 subjects enrolled as of the data cutoff of May 8, 2023, with a range of treatment durations from 18 days to 6 months. Due to batch processing of samples, the data cutoff for PPIX data was April 7, 2023.

Bitopertin was well-tolerated at both dose levels with no reported serious adverse events, no reported discontinuations or dose reductions, no reported adverse events greater than Grade 1, and no meaningful changes observed in mean hemoglobin levels

Bitopertin is an investigational, clinical-stage, orally administered inhibitor of glycine transporter 1 (GlyT1) that is designed to modulate heme biosynthesis. GlyT1 is a membrane transporter expressed on developing red blood cells and is required to supply sufficient glycine for heme biosynthesis and support erythropoiesis. Disc is planning to develop bitopertin as a potential treatment for a range of hematologic diseases including erythropoietic porphyrias, where it has potential to be the first disease-modifying therapy. There are currently two ongoing phase 2 clinical trials of bitopertin in patients with erythropoietic porphyria, including an open-label trial called BEACON and a randomized, double-blind placebo-controlled trial called AURORA. Disc obtained global rights to bitopertin under a license agreement from Roche in May 2021.

“We observed consistent and sustained suppression of PPIX, the disease-causing metabolite in EPP, in patients treated with bitopertin,” said Will Savage, chief medical officer at Disc Medicine. “Importantly, this reduction translated into significant improvements in the time that patients can spend in sunlight without reporting pain or symptoms related to their disease. We’re encouraged by the data and plan to present additional data at the end of the year.”

Photo: John Quisel, CEO and president of Disc Medicine