FDA Grants Accelerated Approval to Alpelisib in PIK3CA-Related Overgrowth Spectrum

Based on results from the EPIK-P1 trial, the FDA has granted accelerated approval to alpelisib for PIK3CA-related overgrowth spectrum.

The FDA has granted accelerated approval to alepelisib (Vijoice) for adult and pediatric patients 2 years or older with severe manifestations of PIK3CA-related overgrowth spectrum (PROS) who require systemic therapy, according to a press release from the FDA.1 

The approval is based off the results of EPIK-P1 (NCT04285723), a single-arm, retrospective chart review of patients who were 2 or older with PROS who were treated with alepelisib. The drug was administered as part of an expanded access program for compassionate use.

PROS is a group of rare disorders that cause overgrowth in the body due to the mutations in the PIK3CA gene.2 Disorders associated with PROS include fibroadipose hyperplasia, CLOVES syndrome, and Megalencephaly-capillary malformation syndrome. Signs and symptoms of PROS include having a larger-than normal brain, low muscle tone, seizures, intellectual disability, and changes in the blood vessels. Since cells are likely to grow and divide more quickly in this population, those with PROs are at an increased risk of developing cancer. Colon, breast, brain, liver, stomach, and lung cancer are the most likely to have PIK3CA mutations among those without PROS.

A total of 37 patients were evaluated with at least 1 target lesion that was observed in imaging at 24 weeks before receiving the first dose of treatment. Results were assessed by independent radiological review and efficacy was defined as a 20% or more reduction in target lesion volume from the baseline in up to 3 lesions; this needed to be confirmed by at lease 1 subsequent imaging assessment.

The recommended dose for patients aged 2 to 18 was 50 mg of alpelisib orally once daily with food. For pediatric patients 6 years and older, the dose can be increased to 125 mg after 24 weeks. The dosing for adult patients 18 years and older is 250 mg orally taken once daily with food.

The primary end point of the study was the proportion of patients with a response at 24 weeks, and the secondary end point was percent of change in the measure of target lesion. Patients were eligible for treatment if they had a documented diagnosis of PROS, evidence of PI3K-mutated gene, and a severe or life-threatening condition where treatment was necessary.

At week 24, 27% (95% CI, 14%-44%) of patients had a radiological response, and 60% had a response the lasted for 10 months or longer. The most common adverse effects observed in 10% or more of patients included diarrhea, stomatitis, and hyperglycemia.

Alpelisib has previously been granted priority review, breakthrough designation, and orphan drug designation for patients with of PIK3CA-realted overgrowth spectrum who require systemic therapy.


  1. FDA approves alpelisib for PIK3CA-related overgrowth spectrum. News Release. FDA. April 5, 2022. Accessed April 6, 2022. https://bit.ly/35M2Swv
  2. National Institute of Health. PIK3CA-related overgrowth spectrum. Revised July 10, 2018. Accessed April 6, 2022. https://bit.ly/3Kk3tEs
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