New oral drug shows big promise in small trial as a porphyria treatment
PORT-77 rapidly reduced a compound's toxic buildup in EPP, XLP patients
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An oral small molecule called PORT-77, being developed to treat two types of porphyria, was found in a small study to rapidly reduce the toxic buildup of a compound known as protoporphyrin IX (PPIX) in blood — suggesting it could become a disease-modifying treatment for these genetic disorders, according to researchers.
Scientists are testing PORT-77 as a potential therapy for erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP), which together are the third most common forms of porphyria. These data come from GATEWAY (NCT06971900), a Phase 2a clinical study sponsored by Portal Therapeutics, an affiliate of Gondolabio
The study’s main goal was to measure changes in PPIX levels in plasma, the clear liquid component of blood, over four days of active dosing with PORT-77 in adults with EPP. With these “positive” results, the “trial met its primary endpoint,” Gondolabio said in a company press release.
“These data represent an important milestone, highlighting PORT-77’s potential to be a disease modifying therapy by significantly reducing PPIX in plasma, the most physiologically relevant blood component for these conditions, which may address the significant unmet need in people living with EPP and XLP,” said Pete Schmidt, MD, Portal’s chief medical officer.
The data were shared at the European Hematology Association (EHA) 2026 Congress, held last month in Stockholm. The poster was titled “Rapid, dose-dependent reduction of plasma protoporphyrin IX with PORT-77 in adults with erythropoietic protoporphyria: Results from the Phase 2a GATEWAY study.”
Building on these data and discussions with the U.S. Food and Drug Administration (FDA), the company said it plans to advance PORT-77 to Phase 2b/3 clinical testing later this year. The developer is intending to launch a study called PATHWAY to test the experimental compound for both EPP and XLP.
Both porphyria types affect the body’s production of heme, an iron-containing molecule that is part of hemoglobin, the protein in red blood cells that carries oxygen. Both EPP and XLP cause PPIX to build up to toxic levels, which can make the skin sensitive to sunlight and cause severe pain, among other symptoms.
PORT-77 is designed to block a protein called ABCG2. This protein helps move PPIX out of red blood cells into circulation and from the liver into bile, a digestive fluid. By blocking ABCG2, PORT-77 is expected to reduce PPIX levels in the bloodstream, acting as a disease-modifying treatment that prevents tissue damage rather than only treating symptoms after they occur.
Trial tested 2 doses of experimental porphyria treatment
In GATEWAY, 19 participants received a placebo followed by an oral suspension of PORT-77 at either 180 mg once daily or 300 mg twice daily for four days. A total of 10 patients received the lower dose, and nine the higher dose.
The main goal was met, with treatment reducing PPIX levels by an average of 63% with the low dose and 79% with the high dose, the data showed. Cuts were seen starting within hours of the first dose, the researchers noted.
“PORT-77 produced rapid, dose-dependent, and highly significant reductions in plasma PPIX,” the team wrote.
We are encouraged by the magnitude and speed of these reductions, which may translate to patients tolerating more time in the sun and improved quality of life.
For Schmidt, the data reflect PORT-77’s potential for “rapid and profound reductions in plasma PPIX within hours of dosing.”
The scientist added: “We are encouraged by the magnitude and speed of these reductions, which may translate to patients tolerating more time in the sun and improved quality of life.”
The treatment was generally well tolerated. No serious side effects were reported, and no patients stopped treatment because of side effects.
“Combined with a favorable safety profile, with no tolerability signals identified, these findings support its continued development as a potential disease-modifying therapy for EPP and XLP,” the researchers wrote.
The company is also running stEPP (NCT07567131), a global observational clinical trial to better understand EPP and XLP. That study is assessing how sensitive patients are to sunlight, time spent outdoors, and changes in circulating PPIX over time. It’s expected to be completed in 2027.
PORT-77 last year was granted orphan drug and fast track designations by the FDA. Orphan drug status supports the development of treatments for rare diseases by offering incentives such as tax credits, fee waivers, and seven years of market exclusivity, should they be approved, while fast track designation accelerates development with closer communication and rolling review.
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