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FDA approves alpelisib for PIK3CA-related overgrowth spectrum

Apr 06 2022


On April 5, 2022, the Food and Drug Administration granted accelerated approval to alpelisib (Vijoice, Novartis Pharmaceuticals) for adult and pediatric patients two years of age and older with severe manifestations of PIK3CA-related overgrowth spectrum (PROS) who require systemic therapy.


Efficacy was evaluated using real-world data from EPIK-P1 (NCT04285723), a single-arm clinical study in patients two years of age and older with PROS who received alpelisib as part of an expanded access program for compassionate use. Eligible patients had clinical manifestations of PROS that were assessed by the treating physicians as severe or life-threatening and necessitating systemic treatment and had documented evidence of mutation in the PIK3CA gene. The efficacy of alpelisib was evaluated in a total of 37 patients with at least one target lesion identified on imaging performed within 24 weeks prior to receipt of the first dose.


The major efficacy outcome measure was the proportion of patients with radiological response at week 24 as determined by blinded independent central radiology review, defined as a ≥20% reduction from baseline in the sum of measurable target lesion volume in up to 3 lesions confirmed by at least 1 subsequent imaging assessment. Duration of response was an additional efficacy outcome measure. Of the 37 patients included in the efficacy population, 27% (95% CI: 14, 44) had a radiological response at week 24. Among responding patients, 60% had a response lasting 12 months or longer.


The most common (≥ 10%) adverse reactions occurring in patients were diarrhea, stomatitis, and hyperglycemia.


The recommended alpelisib dosage for pediatric patients (2 to less than 18 years of age) is 50 mg taken orally once daily with food; for pediatric patients 6 years of age and older, the dose can be increased to 125 mg after 24 weeks if clinically indicated. The recommended dosage for adult patients (≥ 18 years) is 250 mg taken orally once daily with food.




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