Erythropoietic Protoporphyria (EPP) Drug Landscape Heats Up with Disc Medicine's EAP and GondolaBio's Breakthrough Phase 2a Data
The therapeutic development landscape for erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP)—rare genetic disorders causing severe photosensitivity and potential liver damage—is heating up with a major clinical readout from competitor GondolaBio. On June 22, 2026, GondolaBio announced highly positive results from its Phase 2a GATEWAY trial of PORT-77, an investigational oral, small-molecule ABCG2 inhibitor designed to address the root cause of EPP and XLP.
The blinded, randomized, placebo-controlled crossover trial met its primary endpoint, demonstrating rapid, dose-dependent reductions in plasma protoporphyrin IX (PPIX)—the most physiologically relevant biomarker for phototoxicity in EPP. Key findings include:
- Unprecedented Reductions: PORT-77 achieved a massive mean decrease of 79% in plasma PPIX in the high-dose cohort (300 mg BID) and 63% in the low-dose cohort (180 mg QD).
- Rapid Speed to Onset: Reductions in plasma PPIX occurred within hours of the first dose, with no rebound effects observed after dosing was completed.
- Strong Safety Profile: The drug was well tolerated, with no serious adverse events, no treatment discontinuations, and a lower rate of treatment-emergent adverse events (TEAEs) during the active treatment period compared to the placebo period.
Based on these results and alignment with the FDA at an End-of-Phase 2 meeting, GondolaBio plans to launch its global Phase 2b/3 PATHWAY trial in Q3 2026. This trial will directly compete with Disc Medicine's bitopertin, which is currently on a path to address its FDA Complete Response Letter (CRL) using data from its upcoming Phase 3 APOLLO trial. The rapid, deep reductions in plasma PPIX demonstrated by PORT-77 set a high efficacy bar for the EPP space.