Robert Sarkany, MD, FRCP, discusses PORT-77's phase 2a safety profile in EPP and the endpoints to watch as the drug advances to phase 2b/3.
Sarkany discussed results from a placebo-controlled, single-blind crossover study of approximately 19 to 20 patients with EPP dosed with PORT-77 at 2 dose levels over roughly 10 to 14 days, using plasma protoporphyrin concentration as an objective primary endpoint.
At the higher dose, plasma protoporphyrin began falling within 6 hours and reached its full decrease within 4 days, according to Sarkany. He noted the lowest reduction observed was 57%, the average was 79%, and some patients approached a 98% to 99% reduction, with all patients showing a significant, dose-dependent response.
Side effects were minimal across both the phase 2a EPP cohort and a larger phase 1 healthy volunteer population. Sarkany pointed to genetic and mouse model data as additional reassurance, noting individuals with homozygous ABCG2 knockout mutations remain largely healthy aside from mildly elevated uric acid, while ABCG2-null mice with EPP show improved survival compared with mice retaining transporter function.
Sarkany said future trials should assess both skin and liver outcomes, with skin photosensitivity representing the primary clinical endpoint given its near-universal presence in EPP. He said he will be watching for replication of the rapid plasma protoporphyrin reductions seen in phase 2a, along with reductions in phototoxic episodes and improvements in well-being and quality-of-life measures.
Sarkany noted liver-related outcomes are difficult to formally trial given the rarity and delayed onset of hepatic complications in EPP, making pain on sun exposure the primary clinical outcome of interest moving forward.
Editor's Note: This transcript has been edited for grammar and clarity using artificial intelligence tools.
