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FDA has approved Vijoice as first and only treatment for select patients with PIK3CA-related overgrowth spectrum

The U.S. Food and Drug Administration ( FDA ) has granted accelerated approval to Vijoice ( Alpelisib ) for the treatment of adult and pediatric patients 2 years of age and older with severe manifestations of PIK3CA-Related Overgrowth Spectrum ( PROS ) who require systemic therapy.
Vijoice is the first FDA-approved treatment for PROS, a spectrum of rare conditions characterized by overgrowths and blood vessel anomalies impacting an estimated 14 people per million.

PROS conditions can affect quality of life and pose a range of physical, emotional and social challenges for patients and their families, ranging from functional impacts and developmental delays to chronic pain, mobility issues, and feelings of isolation.
PROS management can be challenging, requiring collaboration from a multidisciplinary team, and patients and physicians have only had access to interventions focused on symptom management.

FDA approval was based on real-world evidence from EPIK-P1, a retrospective chart review study that has shown patients treated with Vijoice experienced reduced target lesion volume and improvement in PROS-related symptoms and manifestations.
The primary endpoint analysis conducted at week 24 showed 27% of patients ( 10/37 ) achieved a confirmed response to treatment, defined as 20% or greater reduction in the sum of PROS target lesion volume.
Nearly three in four patients with imaging at baseline and week 24 ( 74%, 23/31 ) have shown some reduction in target lesion volume, with a mean reduction of 13.7%, and no patients experienced disease progression at time of primary analysis.
Additionally, at week 24, investigators observed patient improvements in pain ( 90%, 20/22 ), fatigue ( 76%, 32/42 ), vascular malformation ( 79%, 30/38 ), limb asymmetry ( 69%, 20/29 ), and disseminated intravascular coagulation ( 55%, 16/29 ). These improvements were observed in subsets of patients across the study population ( n=57 ) who reported symptoms at baseline and at week 24.

In EPIK-P1, the most common adverse events of any grade were diarrhea ( 16% ), stomatitis ( 16% ), and hyperglycemia ( 12% ).
The most common grade 3/4 adverse effect was cellulitis ( 4% ); one adult case was considered treatment-related.

The PROS classification was proposed by researchers and parent representatives of patient-family support and advocacy organizations at a National Institutes of Health workshop in 2013 to unite a group of rare overgrowth conditions caused by PIK3CA mutations.
Specific conditions associated with PROS include KTS, CLOVES syndrome, ILM, MCAP/M–CM, HME, HHML, FIL, FAVA, macrodactyly, muscular HH, FAO, CLAPO syndrome and epidermal nevus, benign lichenoid keratosis, or seborrheic keratosis.
The estimated prevalence of PROS conditions is approximately 14 people per million.

Alpelisib is a kinase inhibitor that treats rare overgrowth conditions caused by the effects of PIK3CA mutations in adults and children with PROS.
Alpelisib works by inhibiting the PI3K pathway, predominantly the PI3K-alpha isoform. ( Xagena )

Source: Novartis, 2022