GondolaBio announced that the U.S. Food and Drug Administration has granted both Orphan Drug Designation and Fast Track Designation to PORT-77, an investigational oral small molecule ABCG2 inhibitor developed by its affiliate Portal Therapeutics for the treatment of erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP).
The dual FDA designations represent a significant regulatory milestone for PORT-77, which has the potential to become the first therapy in EPP/XLP that may prevent both skin and liver damage with rapid onset of action. The drug works by inhibiting ABCG2 in both erythrocytes and hepatocytes, targeting the plasma compartment that mediates disease by facilitating deposition of protoporphyrin IX (PPIX) in the skin and liver.
Addressing Critical Unmet Medical Need
"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," said Neil Kumar, Co-founder and CEO of GondolaBio.
EPP and XLP are genetic photodermatoses affecting more than 25,000 people in the U.S. and EU, resulting from the accumulation of protoporphyrin IX. Patients experience cutaneous damage and excruciating pain when exposed to sunlight. Approximately 20-30% of patients with EPP/XLP will experience some type of liver damage, with up to 5% progressing to acute liver failure requiring liver transplant. Currently, no approved disease-modifying treatments are available for these conditions.
Clinical Development Progress
PORT-77 is currently being investigated in the Phase 2A proof-of-concept trial called GATEWAY, with the primary endpoint of plasma PPIX reduction. In preclinical and Phase 1 healthy volunteer studies, PORT-77 demonstrated the ability to significantly lower plasma PPIX, which has the potential to address both the phototoxic and hepatobiliary impacts of EPP and XLP.
The drug showed rapid efficacy with PPIX reduction occurring within hours after dosing via rapid ABCG2 inhibition. No serious adverse events and no safety or tolerability signals have been identified to date in the clinical program.
GondolaBio plans to report full Phase 2 data in the near-term, with Kumar noting that the company's "unique decentralized structure allows us to pursue treatments for rare diseases like EPP and XLP."
Regulatory Benefits and Development Pathway
The Orphan Drug Designation supports development of treatments for rare diseases affecting fewer than 200,000 people in the U.S., providing benefits including potential eligibility for expedited review pathways, tax credits for qualified clinical trials, fee waivers, and seven years of market exclusivity after approval.
Fast Track Designation facilitates development and expedites review of investigational drugs for serious conditions that demonstrate potential to address unmet medical need. Therapeutic candidates with Fast Track Designation may also be eligible for priority review and accelerated approval if supported by clinical data.
PORT-77 is designed as an oral, small molecule ABCG2 inhibitor that limits efflux of PPIX from red blood cells to plasma and from hepatocytes to the biliary tract, representing a potentially disease-modifying, best-in-class treatment addressing the root cause of EPP and XLP. The ongoing clinical program aims to determine if PORT-77 can effectively reduce plasma PPIX to improve sunlight sensitivity and reduce liver damage.
