Novartis' Piqray (Alpelisib) Becomes First FDA-Approved PI3K Inhibitor for PIK3CA-Mutated HR+/HER2- Advanced Breast Cancer
Novartis
Drug Development and Manufacturing
FDA Advisory Committee
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FDA
U.S. Food and Drug Administration
Recently, the U.S. FDA announced the approval of Novartis’ Piqray (alpelisib) for marketing. It is to be used in combination with the endocrine therapy fulvestrant for the treatment of patients with HR+/HER2- advanced or metastatic breast cancer harboring PIK3CA mutations, whose disease has progressed following endocrine therapy. This marks the first PI3K inhibitor approved by the FDA for the treatment of breast cancer. It is also the second innovative therapy approved by the FDA on the same day for Novartis, following the approval of its blockbuster gene therapy Zolgensma. Notably, this is the first new molecular entity (NME) approved by the FDA under the Real-Time Oncology Review (RTOR) pilot program.
In patients with metastatic breast cancer, the tumor has spread to other parts of the body, with the most common sites of metastasis being the bones, lungs, liver, and brain. In HR+/HER2- advanced breast cancer, alterations in the PI3K pathway are the most common cause of tumor progression, disease advancement, and development of treatment resistance. Approximately 40% of patients with HR+/HER2- advanced breast cancer harbor PIK3CA gene mutations.
Piqray is an oral, small-molecule, α-specific PI3K inhibitor developed by Novartis. In breast cancer cell lines harboring PIK3CA gene mutations, it has demonstrated the potential to inhibit the PI3K pathway and suppress cell proliferation.
PI3K is a key oncogenic signaling pathway dysregulated in cancer (Image source: Reference [3])
The FDA approval was based on the performance of Piqray in the Phase 3 clinical trial named SOLAR-1. In this randomized, double-blind, placebo-controlled Phase 3 clinical trial, 572 patients with HR+/HER2- advanced or metastatic breast cancer carrying PIK3CA gene mutations received treatment with either Piqray plus fulvestrant or placebo plus fulvestrant. The trial results demonstrated that, among patients whose tumors harbored PIK3CA gene mutations, the combination therapy of Piqray and fulvestrant significantly improved median progression-free survival compared to the control group (11 months vs. 5.7 months).
“Piqray is the first PI3K inhibitor to demonstrate clinically meaningful efficacy in the treatment of this type of breast cancer. The development of targeted therapies based on patients’ specific genes and biomarkers is becoming increasingly common in the field of cancer treatment,” said Dr. Richard Pazdur, Director of the FDA’s Office of Hematology and Oncology Products. “This drug is also the first innovative therapy approved through the RTOR pilot program.”
References:
[1] FDA approves first PI3K inhibitor for breast cancer. Retrieved May 24, 2019, from https://www.fda.gov/news-events/press-announcements/fda-approves-first-pi3k-inhibitor-breast-cancer
[2] SOLAR-1 trial of Novartis investigational alpha-specific PI3K inhibitor BYL719 (alpelisib) meets primary endpoint in HR+/HER2- advanced breast cancer with PIK3CA mutation. Retrieved May 24, 2019, from https://www.novartis.com/news/media-releases/solar-1-trial-novartis-investigational-alpha-specific-pi3k-inhibitor-byl719-alpelisib-meets-primary-endpoint-hrher2-advanced-breast-cancer-pik3ca-mutation
[3] Meet Novartis Management. Retrieved May 22, 2019, from https://www.novartis.com/sites/www.novartis.com/files/2019-05-meet-novartis-management-presentation.pdf
Source: WuXi AppTec