PORT-77 gets FDA orphan drug, fast track designations for EPP and XLP
Developer says therapy has potential to be disease-modifying for porphyrias
PORT-77, an oral small molecule therapy being developed to treat erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP), by Gondolabio through its affiliate Portal Therapeutics, has been granted both orphan drug and fast track status by the U.S. Food and Drug Administration (FDA).
Orphan drug designation supports therapies for rare diseases — those affecting fewer than 200,000 patients in the U.S. — by offering incentives like tax credits, FDA fee exemptions, and seven years of market exclusivity should a treatment win approval. Fast track designation, meanwhile, accelerates the development of treatments for serious conditions with unmet needs, allowing frequent FDA interaction and a rolling review of applications.
According to Gondolabio, PORT-77 potentially can “prevent both skin and liver damage with [its] rapid onset of action” in people with these two porphyria types, both marked by skin pain that starts after exposure to sunlight.
“For individuals living with protoporphyria, avoiding sunlight is a daily struggle that significantly affects their quality of life. The constant risk of skin and liver damage underscores the urgency of bringing disease-modifying treatments to this population as there remains a great unmet need,” Neil Kumar, cofounder and CEO of Gondolabio, said in a company press release announcing the award of the two FDA designations.
“Gondolabio’s unique decentralized structure allows us to pursue treatments for rare diseases like EPP and XLP, and through these designations, we look forward to further collaboration with FDA as we advance this program,” Kumar added.
EPP and XLP are genetic disorders that, like other types of porphyria, disrupt the body’s ability to produce heme, the molecule that enables red blood cells to carry oxygen.
When heme production is impaired, a key metabolic precursor called protoporphyrin IX, or PPIX, builds up inside red blood cells. It’s released into the bloodstream through transporter proteins such as ABCG2.
Excess PPIX then moves into the skin, causing extreme sensitivity to sunlight or certain artificial light sources, and into the liver, where the same transporter protein releases PPIX into bile, a digestive fluid that helps the body break down fats and eliminate waste products.
Because PPIX is poorly soluble, it can precipitate in bile ducts, forming gallstones and blocking bile flow — a condition known as cholestasis. Over time, this buildup can trigger inflammation, scarring, and progressive liver damage.
PORT-77 now being tested in small trial involving EPP patients
PORT-77 is designed to block ABCG2. By reducing circulating PPIX levels, the therapy aims to mitigate PPIX-mediated skin photosensitivity and liver damage, according to the company.
Gondolabio says PORT-77 has the potential to be a disease-modifying treatment, meaning one that addresses the root cause of EPP and XLP.
The treatment was first tested in preclinical studies. In mouse models of EPP, oral pretreatment with PORT-77 before exposure to light safely prevented light-induced skin damage, which was associated with significantly lower blood PPIX levels. Chronic treatment over eight weeks, or about two months, led to a reduction in liver PPIX buildup and improvements in several markers of progressive liver injury.
In a first-in-human Phase 1 trial (NCT06346509), PORT-77 s’ safety and tolerability are being evaluated in up to 108 healthy adult volunteers. According to the company, the therapy has so far been well tolerated with no serious adverse events or safety signals reported. Early data also suggest reductions in blood PPIX levels within hours after dosing.
PORT-77 is also being tested in the Phase 2a GATEWAY trial (NCT06971900) in up to 14 people with EPP. That study’s primary goal is to measure changes in PPIX blood levels over nine days of treatment.
Secondary objectives include evaluating the therapy’s safety and tolerability, as well as its pharmacokinetics — or how the drug is absorbed, distributed, and cleared from the body.
The company said it plans to report full Phase 2 data in the near term.
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