OBJECTIVES: To model and assess the impact introduction of alpelisib (i.e., world with alpelisib) compared with current standard of care (SoC, i.e., world without alpelisib) would have on surgery rates for the treatment of adult and pediatric patients, 2 years of age and older, with severe manifestations of PIK3CA-related overgrowth spectrum (PROS) in France.

METHODS: We developed a de novo budget impact model (BIM), from the national French health insurance perspective, with a target population in line with that of alpelisib approved indication for PROS in the US. We modeled surgery use over a cumulative 3-year time horizon and estimated the number of surgeries for PROS, i.e., for disease progression (P), for amputation (A) and for disease improvement (I). Surgery rates per person per year before/after initiation of alpelisib (world without/with alpelisib) were obtained from a retrospective non-interventional study (EPIK-P1) and its extension (EPIK-P3). Epidemiology data were obtained from Orphanet and NIH Genetics Home Reference.

RESULTS: In the alpelisib-treated patients only, the rate of surgeries would be reduced by 81% (estimated relative risk (RR) 0.19, (95%CI 0.116 - 0.306)) with a decrease in rates of P (RR 0.02 – 95%CI 0.0024 - 0.079), 100% in A (no CI) and increase in rates of I (RR 7.1 – 95%CI 1.12 - 44.84). Therefore, over a 3-year period, the introduction of alpelisib would be associated with an overall decrease of 104 surgeries for PROS per 100 patients treated with alpelisib.

CONCLUSIONS: There remains a significant unmet medical need for a treatment that can address the underlying cause of PROS, reduce the size of the PROS lesions, and provide an improvement of PROS-related signs and symptoms. Results from the analyses suggest that alpelisib would improve disease management of patients with PROS, reducing the need for surgeries related to disease progression.