Bitopertin Meets Primary Phase 2 Endpoint in Erythropoietic Protoporphyria

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Topline results from AURORA indicate that while bitopertin significantly reduced PPIX levels, improvements in light tolerance were not statistically significant.

Topline data from the phase 2 AURORA study demonstrated the benefit of bitopertin in patients with erythropoietic protoporphyria (EPP), a rare, debilitating disease caused by mutations that affect heme biosynthesis and result in the accumulation of protoporphyrin IX (PPIX).1

Results from AURORA showed treatment with bitopertin led to dose-dependent, statistically significant reductions in PPIX, compared with placebo, across both the 20 mg and 60 mg dosing cohorts. The drug also improved measures of sunlight tolerance in both cohorts, but did not reach statistical significance, given a strong placebo performance.

“This study has confirmed that bitopertin significantly reduces the toxic metabolite, PPIX, in patients with EPP, and we have shown that bitopertin-treated patients experience improvements in the clinically meaningful outcomes of Patient Global Impression of Change (PGIC) and the number and rate of phototoxic reactions with pain, with the 60 mg dose reaching statistical significance compared to placebo,” John Quisel, JD, PhD, president and chief executive officer of Disc Medicine, Inc., said in a statement.1

Patients with EPP experience severe reactions when exposed to sunlight, defined by excruciating pain, edema, burning sensations, and potential blistering and disfigurement.2 As PPIX can accumulate in the hepatobiliary system, nearly 20-30% of patients experience complications, including liver damage, and in extreme cases, liver failure.

Standard of care treatment for EPP typically involves extreme measures to avoid sunlight, including restricting outdoor time to nighttime and protective clothing. These measures have been found to impact psychosocial development, quality of life, and daily activities, particularly for young children and families.

No cure for EPP is currently available—only one US Food and Drug Administration (FDA)-approved therapy exists, afamelanotide (Scenesse), a surgically implanted synthetic hormone, designed to stimulate melanin production.3

Bitopertin, an investigational, clinical-stage, orally administered inhibitor of glycine transporter 1 (GlyT1) designed to modulate heme biosynthesis, has been investigated in two fully-enrolled, ongoing phase 2 trials: the open-label BEACON trial and the randomized AURORA trial.1 The double-blind, placebo-controlled AURORA study involved 75 adult patients with EPP who were randomized 1:1:1 to receive 20 mg bitopertin, 60 mg bitopertin, or placebo, once daily, for 17 weeks of study.

Primary results from AURORA showed treatment with bitopertin led to significant, dose-dependent, and sustained reductions in whole-blood PPIX levels. These data showed a reduction of –21.6% for the 20 mg cohort (P = .003) and –40.7% for the 60 mg cohort (P <.001), and a mean increase of +8.0% in the placebo cohort.

AURORA also measured the cumulative total time in sunlight between 10 am and 6 pm on the day without pain with bitopertin treatment during the 4-month treatment period. Cumulative time in sunlight was a mean of 175.1 hours at the 20 mg dose level and 153.1 hours at the 60 mg dose level, compared with 133.9 hours for placebo, and did not reach statistical significance.

The company indicated the improvement in the bitopertin treatment arms was comparable to results from BEACON, but the benefit in the placebo arm in AURORA was larger than anticipated.

Other secondary end points revealed substantial and dose-dependent reductions in the rate of phototoxic reactions with pain during the study period. Analyses showed a 75% reduction in the incidence rate of new phototoxic reactions with pain at the 60 mg dose group, compared with placebo (P = .011), and a 60% reduction at the 20 mg dose level (P = .109).

Dose-dependent improvements were identified in the PGIC, with statistical significance achieved at the 60 mg dose. Data showed 77% of completers at the 20 mg and 86% at the 60 mg dose levels (P = .022) reported their EPP was “much better” than 50% of the placebo cohort.

Overall, the drug was well-tolerated at both dosing levels and patients treated with bitopertin experienced no serious adverse events and stable hemoglobin levels.

“Despite the strong performance of bitopertin on the key secondary endpoint of cumulative time in light, consistent with results seen in BEACON, statistical significance was not met due to an outsized placebo response,” Quisel added. “Given that, we will need to conduct an analysis of our final data set and work with investigators, regulators, and patient advocacy groups to define the optimal registrational endpoints moving forward.”


  1. Disc reports topline results from Phase 2 Aurora Study of Bitopertin in patients with Erythropoietic protoporphyria (EPP). Disc Medicine Inc. April 1, 2024. Accessed April 1, 2024.
  2. Erythropoietic protoporphyria. StatPearls [Internet]. February 16, 2023. Accessed April 1, 2024.
  3. Commissioner O of the. 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 April 1, 2024.