FDA Approves Celcuity’s Revtorpyk for PI3K-Pathway Targeted Breast Cancer Treatment

The approval of Revtorpyk (gedatolisib) gives Celcuity a new treatment option for HR-positive, HER2-negative breast cancer patients without PIK3CA mutations, following positive Phase III VIKTORIA-1 data showing improved progression-free survival.

Celcuity has received approval from the US Food and Drug Administration (FDA) for Revtorpyk (gedatolisib), a targeted therapy designed to inhibit the PI3K/AKT/mTOR (PAM) signalling pathway in certain patients with advanced breast cancer.

The therapy has been approved in combination with fulvestrant, with or without Pfizer’s Ibrance (palbociclib), for adults with:

• Hormone receptor-positive (HR-positive)

• HER2-negative

• Locally advanced or metastatic breast cancer

• Second-line or later disease

• No PIK3CA mutation
  

The approval represents a new treatment approach for a subset of breast cancer patients who have historically had limited targeted therapy options.

Following the regulatory decision, Celcuity shares initially increased by approximately 7% before giving back most gains in after-hours trading.

How Revtorpyk Works in Breast Cancer

Revtorpyk is an intravenously administered comprehensive inhibitor of the PI3K/AKT/mTOR pathway, a signalling network involved in cancer cell growth, survival and treatment resistance.

The PI3K pathway is one of the most frequently altered pathways in breast cancer, particularly in HR-positive, HER2-negative disease.

Approximately 70% of breast cancers are HR-positive, HER2-negative, and around 40% of these tumours contain PIK3CA mutations.

Unlike therapies targeting individual components of the pathway, Celcuity’s approach is designed to inhibit multiple signalling nodes within the PAM pathway.

Phase III VIKTORIA-1 Trial Supports FDA Approval

The FDA approval was supported by data from the Phase III VIKTORIA-1 trial, which evaluated Revtorpyk in patients with advanced HR-positive, HER2-negative breast cancer.

The study enrolled 701 patients across both:

• PIK3CA-mutant tumours

• PIK3CA wild-type tumours
  

Participants were randomised to receive:

• Revtorpyk plus fulvestrant and Ibrance

• Revtorpyk plus fulvestrant

• Fulvestrant alone
  

Both patient populations met the trial’s primary endpoint of progression-free survival (PFS).

The FDA submission focused initially on the PIK3CA wild-type population, which received priority review earlier this year.

Revtorpyk Demonstrated Progression-Free Survival Benefit in Wild-Type Breast Cancer

In the PIK3CA wild-type cohort, Celcuity reported significant improvements with Revtorpyk-based treatment combinations.

The triplet combination of:

• Revtorpyk

• Fulvestrant

• Ibrance
  

reduced the risk of disease progression compared with fulvestrant alone.

Key results included:

Treatment	Median Progression-Free Survival
Revtorpyk + fulvestrant + Ibrance	9.3 months
Fulvestrant alone	2 months

This represented a 76% improvement in progression-free survival compared with fulvestrant monotherapy.

The Revtorpyk and fulvestrant combination also demonstrated statistically significant benefit, achieving a median PFS of 7.4 months.

Objective response rates were:

• 32% for Revtorpyk + fulvestrant + Ibrance

• 28% for Revtorpyk + fulvestrant

• 1% for fulvestrant alone
  

Additional Opportunity in PIK3CA-Mutated Breast Cancer

Celcuity is also pursuing a potential expansion into PIK3CA-mutated breast cancer, where Revtorpyk demonstrated positive results in the VIKTORIA-1 trial.

In this patient group, the comparator was:

• Novartis’ PI3Kα inhibitor Piqray (alpelisib) plus fulvestrant
  

Presented data showed:

• Revtorpyk triplet therapy reduced the risk of disease progression or death by 50%

• Revtorpyk plus fulvestrant reduced the risk by 49%

Median progression-free survival was:

Treatment	Median PFS
Revtorpyk + fulvestrant + Ibrance	11.1 months
Revtorpyk + fulvestrant	11.3 months
Piqray + fulvestrant	5.6 months

Celcuity announced plans to submit a supplemental regulatory application based on these findings.

Challenges Remain Around Intravenous Delivery

Despite positive clinical results, questions remain around how Revtorpyk will compete in a treatment landscape increasingly focused on convenience and patient quality of life.

Unlike many modern targeted therapies that are administered orally, Revtorpyk requires intravenous delivery.

Some clinicians have highlighted this as a potential limitation, particularly in a disease setting where patients may prefer treatments that reduce hospital visits.

Denise Yardley, associate director of breast cancer research at Sarah Cannon Research Institute, noted that while Revtorpyk appeared more effective than Piqray, intravenous administration could create challenges for adoption.

She also highlighted that PI3K-targeting therapies can be difficult to use due to side effects including:

• Rash

• Diarrhoea

• Hyperglycaemia
  

The Future of PI3K-Targeted Breast Cancer Treatment

Revtorpyk enters a competitive breast cancer market where pharmaceutical companies continue to develop increasingly targeted approaches based on tumour biology.

The approval reinforces the importance of pathway-based therapies in HR-positive, HER2-negative breast cancer, particularly for patients whose tumours do not contain traditional actionable mutations.

For Celcuity, future success will depend on balancing clinical benefit with practical considerations such as administration burden, tolerability and positioning against established targeted therapies.

Summary

The FDA has approved Celcuity’s Revtorpyk (gedatolisib) for adults with HR-positive, HER2-negative advanced breast cancer without PIK3CA mutations.

Supported by Phase III VIKTORIA-1 data, the therapy demonstrated improved progression-free survival when combined with fulvestrant, with or without Ibrance.

While the approval expands treatment options for patients with limited alternatives, Celcuity will need to overcome challenges around intravenous delivery and the broader tolerability concerns associated with PI3K-targeting therapies as it seeks commercial adoption.

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