On April 5, 2022, the U.S. Food and Drug Administration (FDA) granted accelerated approval to alpelisib (Vijoice®) for adult and pediatric patients aged two and older with severe manifestations of PIK3CA-related overgrowth spectrum (PROS) who require systemic therapy.
Efficacy was evaluated using real-world data from a single-arm clinical study (EPIK-P1; NCT04285723) in patients aged two and older with PROS who received alpelisib as part of an expanded access program for compassionate use. A total of 37 patients had clinical manifestations of PROS that were assessed by treating physicians as severe or life-threatening and necessitating systemic treatment and had documented evidence of a PIK3CA variant. Patients had at least one target lesion identified on imaging performed within 24 weeks prior to the first dose.
The major efficacy outcome measure was the proportion of patients with radiologic response at week 24 as determined by blinded independent central radiology review, defined as a 20% or more reduction from baseline in the measurable target lesion volume in up to three lesions confirmed by at least one subsequent imaging assessment. Duration of response was an additional efficacy outcome measure. Of the 37 patients, 27% (95% CI = 14, 44) had a radiologic response at week 24, with 60% lasting 12 months or longer.
The most common adverse reactions reported in 10% or more of patients were diarrhea, stomatitis, and hyperglycemia.
The recommended alpelisib dosage for pediatric patients aged 2–18 years is 50 mg taken orally once daily with food. For pediatric patients aged 6 and older, the dose can be increased to 125 mg after 24 weeks if clinically indicated. The recommended dosage for adult patients aged 18 years or more is 250 mg taken orally once daily with food.
The review used the Real-Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment.
The application was granted priority review, breakthrough designation, and orphan drug designation. A description of FDA expedited programs is in the Guidance for Industry—Expedited Programs for Serious Conditions—Drugs and Biologics.
Healthcare professionals should report all serious adverse events they suspect are associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.
For assistance with single-patient investigational new drug applications for oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.