The 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.
PROS is a group of rare disorders characterized by overgrowths and blood vessel anomalies due to mutations in the PIK3CA gene. Vijoice is an inhibitor of phosphatidylinositol-3-kinase (PI3K), predominantly the PI3K-alpha isoform. Inhibition of the PI3K pathway may result in the prevention or improvement of organ abnormalities associated with these disorders.
The approval was based on real-world evidence from a global, site-based, retrospective, non-interventional medical chart review of the EPIK-P1 trial (ClinicalTrials.gov Identifier: NCT04285723), which included 57 patients aged 2 years or older with PROS who were treated with Vijoice 50mg to 250mg orally once daily as part of an expanded access program for compassionate use.
The primary endpoint was the proportion of patients with radiological response at week 24, defined as achieving at least a 20% reduction from baseline in the sum of measurable target lesion volume (1 to 3 lesions), confirmed by at least 1 subsequent imaging assessment, in the absence of a 20% or greater increase from baseline in any target lesion, progression of non-target lesions, or appearance of a new lesion.
Among 37 efficacy evaluable patients, results showed that 27% (n=10/37; 95% CI, 14-44) had a confirmed response at week 24. The median duration of response was not reached (95% CI, 0.9+, 42.9+ months), with 70% of patients having a response duration of at least 6 months and 60% having a response duration of at least 12 months. Moreover, 74% (n=23/31) of patients with imaging at baseline showed a mean reduction of 13.7% in target lesion volume. None of the patients experienced disease progression at the time of primary analysis.
At week 24, improvements in pain (90%; n=20/22), fatigue (76%; n=32/42), vascular malformation (79%; n=30/38), limb asymmetry (69%; n=20/29), and disseminated intravascular coagulation (55%; n=16/29) were observed.
The most common adverse reactions reported were diarrhea (16%), stomatitis (16%), and hyperglycemia (12%). The most common grade 3/4 adverse event was cellulitis. Additionally, severe hypersensitivity, severe cutaneous adverse reactions, and pneumonitis have been reported with the use of alpelisib.
Continued approval of Vijoice may be contingent upon verification and description of clinical benefit in a confirmatory trial. The accelerated approval was based on response rate and duration of response.
Vijoice is supplied as 50mg, 125mg, and 200mg tablets. For patients with difficulty swallowing, the tablets can be used to prepare an oral suspension.
The product is expected to be available in the coming week.
- FDA approves Novartis Vijoice® (alpelisib) as first and only treatment for select patients with PIK3CA-Related Overgrowth Spectrum (PROS). News release. Novartis Pharmaceuticals Corporation. Accessed April 6, 2022. https://www.multivu.com/players/English/9015251-fda-approves-novartis-vijoice-as-treatment-for-pros/
- Vijoice. Package insert. Novartis Pharmaceuticals Corporation; 2022. Accessed April 6, 2022. https://www.novartis.us/sites/www.novartis.us/files/vijoice.pdf