Phase 2 AURORA Trial Demonstrates Clinical Activity of Bitopertin for EPP


Bitopertin achieves significant reductions in PPIX versus placebo in patients with erythropoietic protoporphyria.

Phase 2 AURORA Trial Demonstrates Clinical Activity of Bitopertin for EPP | Image Credit: Disc Medicine

John Quisel, JD, PhD

Credit: Disc Medicine

An updated analysis from the Phase 2 AURORA study demonstrates the potential clinical benefit of bitopertin for erythropoietic protoporphyria (EPP), according to data presented at the European Hematology Association (EHA) 2024 Hybrid Congress.1

Announced by Disc Medicine on June 14, 2024, these data highlighted meaningful improvement in light tolerance, phototoxic reactions, and quality of life among patients with EPP treated with the investigational drug.

“This has been a tremendously exciting EHA meeting for Disc, where we had the opportunity to present data from ongoing clinical studies across our entire portfolio, showcasing the activity and therapeutic potential of each of our programs,” said John Quisel, JD, PhD, president and chief executive officer of Disc.1

EPP is a rare, debilitating disease caused by mutations that affect heme biosynthesis and result in the accumulation of protoporphyrin IX (PPIX).2 Individuals with EPP deal with severe reactions after sunlight exposure, including pain, edema, burning sensations, and the potential for blistering and disfigurement.

When PPIX accumulates in the hepatobiliary system, more than 1 in 5 patients can experience disease complications, including liver damage and liver failure. Standard care for EPP usually involves extreme measures to avoid sunlight, including outdoor restrictions and protective clothing. These measures can impact psychosocial development and quality of life, especially for children and families.

Without a cure, only a single US Food and Drug Administration (FDA) therapy is approved for the condition — afamelanotide (Scenesse) is a surgically implanted synthetic hormone, designed to stimulate melanin production.3

Bitopertin is an investigational, clinical-stage, orally administered inhibitor of glycine transporter 1 (GlyT1) designed to modulate heme biosynthesis.1 AURORA is a randomized, double-blind, placebo-controlled Phase 2 trial that enrolled 75 adults with EPP to bitopertin or placebo treatment.

Participants were randomized 1:1:1 to receive 20 mg bitopertin (n = 26), 60 mg bitopertin (n = 25), or placebo (n = 24) once daily for 17 weeks. Analyses revealed significant reductions in PPIX with bitopertin compared with placebo, approximately 40% for the 60 mg cohort.

Bitopertin also demonstrated meaningful improvement across key measures of EPP. Time-dependent improvement in light tolerance achieved nominal significance versus placebo across the 20 mg (P = .026) and 60 (P = .013) dose cohorts.

Meanwhile, a posthoc longitudinal analysis revealed a two-fold improvement in light tolerance compared with baseline in the 20 and 60 mg bitopertin dose cohorts. Bitopertin had meaningful, dose-dependent reductions in the rate of phototoxic reactions, compared with placebo, and achieved statistical significance in the 60 mg dose cohort (–75.3%; P = .011).

In addition, dose-dependent improvements in the Patient Global Impression of Change (PGIC) were statistically significant for the bitopertin 60 mg dose (P = .022).

The release indicated the evaluation of the time course of phototoxic reactions and exposure to sunlight demonstrated a larger treatment effect in the period after the PPIX nadir was achieved. This included eliminating observed phototoxic reactions in the bitopertin 60 mg dose cohort.

Overall, higher reductions in PPIX were linked to improvements in light tolerance measures, including cumulative total time in light, average time in sunlight without pain, and the change from baseline in time to prodrome.

Safety results demonstrated the strong tolerability of bitopertin for EPP, with the data reporting no serious adverse events to date.

Disc Medicine indicated the full adult data set from the open-label, Phase 2 BEACON trial was also presented at EHA, showing consistent effects as previously presented results and similar clinical activity to AURORA.1

“At this meeting, we shared a deeper analysis of data from AURORA that underscores our confidence in bitopertin’s potential in EPP and supports a development path forward,” Quisel added.1


  1. Disc medicine presents positive clinical data across portfolio at the European Hematology Association (EHA) 2024 Congress. Disc Medicine Inc. June 14, 2024. Accessed June 18, 2024.
  2. Ahmed jan N, Masood S. Erythropoietic Protoporphyria. [Updated 2023 Feb 16]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from:
  3. FDA approves first treatment to increase pain-free light exposure in patients with a rare disorder. U.S. Food and Drug Administration. October 8, 2019. Accessed June 18, 2024.
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