Red section header with a faint illustration of a cellular membrane and receptor embedded in the membrane on the right side

Mechanism of Action

PIK3CA mutations lead to hyperactivation of PI3Kα, a key upstream component of the PI3K pathway¹

The PIK3CA gene codes for the catalytic α-subunit of the PI3K protein (PI3Kα)
Mutations to this gene lead to activation of PI3Kα and Akt-signaling, cellular transformation, and the generation of tumors in in vitro and in vivo models

Green oval with "mTOR" centered in white font and Green oval with "Akt" centered in white font

Inhibiting PI3K interrupts various downstream signaling, including Akt/mTOR and Akt-independent cascades^1,2

In a preclinical mouse model, inhibition of PI3K with alpelisib was shown to reduce the size of overgrowth and reduce proliferation²
In an inducible mouse model of CLOVES syndrome, inhibition of the PI3K pathway with alpelisib resulted in the prevention or improvement of organ abnormalities associated with the disease, depending on when treatment with alpelisib was started. These findings were reversed after withdrawal of alpelisib¹

Based on in vitro/in vivo studies.¹ Preclinical activity does not necessarily correlate with clinical outcomes.

VIJOICE does not suppress the immune system.^1-5

VIJOICE targets the underlying cause of PROS^1,6,7

VIJOICE is an α-selective PI3K inhibitor¹
VIJOICE inhibits the α isoform of PI3K 50 times more potently than other PI3K isoforms (β, γ, δ)⁷

SEE HOW VIJOICE TARGETS THE ROOT CAUSE OF PROS

mTOR, Mechanistic Target of Rapamycin; AKT, Protein Kinase B (PKB).

References:
1. Vijoice. Prescribing information. Novartis Pharmaceuticals Corp.
2. Venot Q, Blanc T, Rabia SH, et al. Targeted therapy in patients with PIK3CA-related overgrowth syndrome. Nature. 2018;558(7711):540-546. doi:10.1038/s41586-018-0217-9
3. Huijts CM, Santegoets SJ, Quiles del Rey M, et al. Differential effects of inhibitors of the PI3K/mTOR pathway on the expansion and functionality of regulatory T cells. Clin Immunol. 2016;168:47-54. doi:10.1016/j.clim.2016.05.005
4. Pagliazzi A, Oranges T, Traficante G, et al. PIK3CA-related overgrowth spectrum from diagnosis to targeted therapy: a case of CLOVES syndrome treated with alpelisib. Front Pediatr. 2021;9:1-6. doi:10.3389/fped.2021.732836
5. Sun P, Meng L-H. Emerging roles of class I PI3K inhibitors in modulating tumor microenvironment and immunity. Acta Pharmacol Sin. 2020;41(11):1395-1402. doi:10.1038/s41401-020-00500-8
6. Keppler-Noreuil KM, Rios JJ, Parker VER, et al. PIK3CA-related overgrowth spectrum (PROS): diagnostic and testing eligibility criteria, differential diagnosis, and evaluation. Am J Med Genet A. 2015;167A(2):287-295. doi:10.1002/ajmg.a.36836
7. Data on file. Study CBYL719F12002 (EPIK-P1) Clinical Study Report. Novartis Pharmaceuticals Corp; 2021.