Phase 2 AURORA Trial: Bitopertin's Impact on EPP Patients

Disc Medicine, a biopharmaceutical firm, has shared initial findings from its phase 2 AURORA trial of bitopertin for treating patients with erythropoietic protoporphyria (EPP). The trial showed that bitopertin led to a significant decrease in protoporphyrin IX (PPIX) levels, the primary goal of the study, and improvements in light tolerance and phototoxic reactions, although the latter did not reach statistical significance. The 60 mg dose demonstrated a notable reduction in phototoxic reactions with pain and improvements in the Patient Global Impression of Change (PGIC), achieving statistical significance over the placebo.

The AURORA study was a randomized, double-blind, placebo-controlled phase 2 trial that included 75 adults with EPP. Participants were divided into three groups to receive either 20 mg or 60 mg of bitopertin or a placebo daily for 17 weeks. The primary endpoint showed a significant reduction in whole blood PPIX levels with bitopertin treatment: -21.6% for the 20 mg dose and -40.7% for the 60 mg dose, compared to an increase of +8.0% in the placebo group.

Secondary endpoints indicated that bitopertin-treated patients had more time in sunlight without pain, but this did not reach statistical significance due to a strong placebo effect. Light tolerance improved in both bitopertin groups, but again, this was not statistically significant. Phototoxic reactions with pain were significantly reduced in the 60 mg group, with a 75% reduction in incidence rate compared to the placebo. The PGIC saw improvements, especially in the 60 mg group, where 86% of patients reported their condition as "much better."

Bitopertin was generally well-tolerated, with no serious adverse events and stable hemoglobin levels. Two patients in the 60 mg group discontinued treatment due to adverse events. The most commonly reported adverse event was dizziness.

Disc Medicine is committed to developing novel treatments for serious hematologic diseases. The company is currently analyzing the final data set and will work with various stakeholders to define the optimal endpoints for future trials. Disc Medicine also anticipates updates from other ongoing studies, such as the DISC-0974 trial for anemia of myelofibrosis.

Bitopertin is an investigational drug and not yet approved for use. It is an orally-administered inhibitor of glycine transporter 1 (GlyT1), which may modulate heme biosynthesis. Disc Medicine obtained the rights to bitopertin from Roche in May 2021.

EPP and X-linked Protoporphyria (XLP) are rare and severe diseases caused by mutations affecting heme biosynthesis, leading to the accumulation of PPIX and causing severe reactions to sunlight. The standard of care currently involves avoiding sunlight and managing pain, significantly impacting patients' quality of life. There is currently no cure for EPP, and only one FDA-approved therapy exists.

Disc Medicine is focused on discovering and developing innovative treatments targeting red blood cell biology, specifically heme biosynthesis and iron homeostasis. The company's commitment to hematologic diseases aims to bring about potentially first-in-class therapeutic candidates.