Disc Reports Positive Initial Data from Phase 2 Study in Rare Blood Diseases

Rare Daily Staff

Disc Medicine reported positive data from its phase 2, open-label BEACON trial evaluating its experimental therapy bitopertin in patients with the rare blood disorders erythropoietic protoporphyria and X-linked protoporphyria.

The initial trial data demonstrated consistent decreases in PPIX, significant increases in reported sunlight tolerance and improvements in measures of patient quality of life.

“We’re delighted to share these initial, positive data from BEACON, which provide the first clinical evidence supporting our therapeutic hypothesis of bitopertin in EPP,” said John Quisel, president and CEO of Disc Medicine. “Over the next 12 months, we plan to build on this momentum with a series of additional clinical read-outs across our portfolio.”

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.

Bitopertin is an experimental, 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.

The study showed significant, consistent, dose-dependent, and sustained reductions of whole-blood, metal-free protoporphyrin IX (PPIX) levels with mean reduction of greater than 40 percent when compared to baseline.

Measures of light tolerance from two participants with the longest follow-up demonstrated substantial increases in sunlight tolerance as measured by time in sunlight without experiencing a prodrome (initial symptoms that signal a pain attack), or “sunlight challenge.”

A participant on 20 mg bitopertin reported a greater than 80-fold increase in sunlight tolerance on day 88 of treatment, increasing from 4.5 minutes at baseline to over 6 hours. The participant did not report a prodrome during any sunlight challenge after Day 20

A participant on 60 mg bitopertin reported a greater than 200-fold increase in sunlight tolerance on day 74 of treatment, increasing from 1.25 minutes at baseline to more than four hours, and did not report a prodrome during any sunlight challenge after Day 120.

Measures of light tolerance aggregated across participants from whom data was available in the trial found an average weekly total time spent in sunlight increased from 344 minutes (approximately 49 minutes per day) to 1,200 minutes at Week 24.

Time to prodrome during sunlight challenge (averaged over a two-week period): increased more than 7-fold, from 25 minutes at baseline to 182 minutes at Week 24

There was a 96 percent reduction in patient-reported phototoxic reactions while on treatment compared to baseline.

All 10 patients that had completed a day 43 visit reported their disease was much better or a little better in the last 7 days.

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.

These data were presented at the European Hematology Association 2023 Congress in Frankfurt, Germany.

Photo: John Quisel, president and CEO of Disc Medicine