The FDA has approved Celcuity‘s REVTORPYK (gedatolisib) for HR+/HER2-, locally advanced or metastatic breast cancer without a PIK3CA mutation, following progression on or after at least one line of endocrine therapy in the metastatic setting. It is used in combination with fulvestrant, with or without palbociclib. REVTORPYK is the first and only FDA-approved therapy to inhibit all class I PI3K isoforms (alpha, beta, delta, gamma) and both mTOR complexes (mTORC1 and mTORC2).
The approval targets a large patient population. HR+/HER2- is the most common breast cancer subtype at roughly 70% of all cases, and about 60% of those are PIK3CA wild-type – a group with few targeted options after endocrine therapy fails.
Approval was based on the PIK3CA wild-type cohort of the Phase 3 VIKTORIA-1 trial. The REVTORPYK triplet (with palbociclib and fulvestrant) delivered median progression-free survival of 9.3 months versus 2.0 months for fulvestrant alone – a 76% reduction in the risk of disease progression or death – with an objective response rate of 32% versus 1%. The doublet (with fulvestrant) reached median PFS of 7.4 months, a 67% risk reduction.
“The PI3K/AKT/mTOR, or PAM, pathway is one of the most important targets in cancer, but comprehensively inhibiting it has stymied researchers and drug developers for nearly two decades,” said Celcuity CEO and co-founder Brian Sullivan. “REVTORPYK addressed this 20-year challenge by becoming the first pan-PI3K, mTORC1/2 inhibitor approved by the FDA.”
The therapy carries notable safety considerations, including high rates of stomatitis (72% with the triplet), rash, and hyperglycemia, requiring prophylactic mouthwash and glucose monitoring. It also carries a risk of embryo-fetal toxicity, with contraception advised during treatment.
Celcuity expects commercial launch in late Q3 2026 and plans to submit a supplemental application for the PIK3CA-mutated population based on the mutant cohort of VIKTORIA-1, presented at the 2026 ASCO Annual Meeting. The therapy is also being evaluated in first-line settings through the ongoing Phase 3 VIKTORIA-2 program.
