Buparlisibi

Drug Overview

Buparlisib (Novartis) is a pan-phosphoinositide 3-kinase (PI3K) inhibitor that attempts to counteract the dysregulation of the PI3K/protein kinase B (AKT) pathway in cancerous tissues. Mechanisms that contribute to PI3K dysregulation include aberrant activation of upstream receptors of PI3K, amplification mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene that encodes the catalytic subunit of PI3K, as well as inactivation of the phosphatase and tensin homolog tumor suppressor protein. PI3K signaling plays a fundamental role in tumorigenesis, governing cell proliferation, survival, and motility, as well as angiogenesis.

Analyst Outlook

Novartis is attempting to position its phosphoinositide 3-kinase (PI3K) inhibitors buparlisib and alpelisib as the standard option for PI3K-mutated breast cancers, which represents the most common molecular mutation subtype in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer patients. If approved, buparlisib will be indicated as a combination therapy with Faslodex (fulvestrant; AstraZeneca). The Phase III BELLE-2 trial of buparlisib plus Faslodex met its primary endpoint of increasing progression-free survival (PFS) in relapsed hormone-resistant HR+/HER2- breast cancer patients, indicating that the combination could meet some of the high unmet need in this patient population.