Regulatory & Policy

Celcuity seeks to expand Revtorpyk label to PIK3CA-mutant breast cancer after beating alpelisib

Celcuity seeks to expand Revtorpyk label to PIK3CA-mutant breast cancer after beating alpelisib

Minneapolis-based Celcuity Inc. (Nasdaq: CELC) submitted a supplemental New Drug Application (sNDA) to the US FDA for Revtorpyk (gedatolisib), seeking approval in patients with hormone receptor-positive (HR+), HER2-negative, locally advanced or metastatic breast cancer harboring a PIK3CA mutation, following progression on at least one prior line of endocrine therapy. If approved, the filing would extend Revtorpyk's label to cover both PIK3CA-mutant and wild-type disease, encompassing the full HR+/HER2- advanced breast cancer population in the second-line setting.

The application arrives six weeks after the FDA approved Revtorpyk on July 14, 2026 for the PIK3CA wild-type subset of the same indication. That approval, based on the wild-type cohort of the Phase III VIKTORIA-1 trial, established Revtorpyk as the first pan-PI3K and mTORC1/2 inhibitor to receive FDA clearance. The current sNDA is supported by the PIK3CA-mutant cohort of the same trial, in which gedatolisib was compared directly against alpelisib plus fulvestrant — an established targeted regimen for PIK3CA-mutant disease — rather than against fulvestrant alone.

In the 350-patient PIK3CA-mutant cohort of VIKTORIA-1, the Revtorpyk triplet (gedatolisib plus fulvestrant and palbociclib) reduced the risk of disease progression or death by 50% compared with alpelisib plus fulvestrant (HR=0.50; 95% CI: 0.37–0.68; p<0.0001), with median progression-free survival (PFS) of 11.1 months versus 5.6 months. The Revtorpyk doublet (gedatolisib plus fulvestrant) produced a comparable reduction in risk (HR=0.51; 95% CI: 0.33–0.79; descriptive p=0.0013), with median PFS of 11.3 months. Objective response rates were 49% and 36% for the triplet and doublet, respectively, with median durations of response of 15.7 and 24.2 months. The company said the safety profile was consistent with data previously reported from the wild-type cohort.

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Three targeted treatment options currently hold FDA approval for molecularly selected HR+/HER2- advanced breast cancer populations that include PIK3CA mutations: Novartis's alpelisib (Piqray), AstraZeneca's capivasertib (Truqap), and Roche's inavolisib (Itovebi). Gedatolisib's pan-isoform mechanism — inhibiting all four class I PI3K isoforms alongside mTORC1 and mTORC2 — is designed to eliminate the pathway escape routes that single-node inhibitors may leave open, though no head-to-head data against capivasertib or inavolisib exist.

PIK3CA mutations occur in approximately 40% of HR+/HER2- metastatic breast cancers, representing a commercially material subset of the most common breast cancer subtype. Celcuity said it intends to submit the VIKTORIA-1 data to other regulatory authorities following the sNDA submission.


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