Bitopertin shows efficacy in patients with erythropoietic protoporphyria: Results from the randomized, double-blind, placebo-controlled AURORA trial

Background Erythropoietic protoporphyria is a rare genetic disorder of heme biosynthesis characterized by protoporphyrin-IX accumulation, painful phototoxic reactions, and hepatobiliary disease, for which no disease-modifying therapies are approved. Objective To evaluate the efficacy and safety of bitopertin, an inhibitor of glycine transporter 1, in adults with erythropoietic protoporphyria. Methods In this randomized, double-blind, phase 2 study, patients received once-daily oral bitopertin 20 mg, bitopertin 60 mg, or placebo for 17 weeks. The primary endpoint was percentage change from baseline in whole-blood metal-free protoporphyrin-IX levels at day 121. Results Patients received bitopertin 20 mg ( n = 26), 60 mg ( n = 25), or placebo ( n = 24). At day 121, the percentage change from baseline in whole-blood metal-free protoporphyrin-IX versus placebo was −29.6% ( P = .004) with bitopertin 20 mg and −49.8% ( P < .001) with bitopertin 60 mg. Bitopertin was associated with a reduced incidence of phototoxic reactions. Bitopertin was well tolerated with no notable safety concerns identified. Limitations Small sample size, short follow-up period, and no formal adjustments for between-group multiple-pairwise comparisons. Conclusions Bitopertin significantly reduced protoporphyrin-IX levels, showed improved measures of sunlight tolerance, and had a favorable safety profile in patients with erythropoietic protoporphyria.