Novartis’ PI3K Inhibitor Piqray Receives Positive CHMP Opinion for First-Ever Targeted Therapy in PIK3CA-Mutated HR+/HER2- Advanced Breast Cancer

Jun 02, 2020 15:15 CST Updated 15:15

Novartis

Drug Development and Manufacturing

European Medicines Agency

The European Medicines Agency (EMA) is a decentralized agency of the European Union (EU), located in London. It began operations in 1995. The agency is responsible for the scientific evaluation, supervision, and safety monitoring of medicines developed by pharmaceutical companies for use in the EU. By ensuring that all medicines available on the EU market are safe, effective, and of high quality, the EMA protects public and animal health in the 28 EU Member States and countries of the European Economic Area.

Committee for Medicinal Products for Human Use

Committee for Medicinal Products for Human Use (CHMP)The Committee for Medicinal Products for Human Use (CHMP) is the committee within the European Medicines Agency (EMA) responsible for human medicines. The CHMP replaced the former Committee for Proprietary Medicinal Products (CPMP) in May 2004.The CHMP plays a vital role in the authorization of medicines in the European Union (EU). In the centralized procedure, the CHMP is responsible for: 1) conducting initial assessments of marketing authorization applications across the EU; assessing modifications or extensions to existing marketing authorizations (“variations”); considering recommendations from the Agency’s Pharmacovigilance Risk Assessment Committee regarding the safety of medicines on the market, and, where necessary, advising the European Commission to amend the marketing authorization of a medicinal product, or to suspend or withdraw it from the market.The CHMP also evaluates medicines authorized at the national level that are referred to the EMA, with the aim of maintaining a harmonized position throughout the EU.Furthermore, the CHMP and its working groups promote the development of medicines and pharmaceutical regulation by: providing scientific advice to companies researching and developing new medicines; developing scientific and regulatory guidelines to assist pharmaceutical companies in preparing marketing authorization applications for human medicines; and collaborating with international partners to harmonize regulatory requirements.

June 02, 2020 /Bio ValleyBIOON/ --Novartis(Novartis) recently announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion, recommending the approval of Piqray (alpelisib) in combination with fulvestrant for the treatment of postmenopausal women and menBreast CancerPatients, specifically: those with locally advanced or metastatic breast cancer who are hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-), harbor PIK3CA mutations, and have experienced disease progression after receiving endocrine monotherapy.

The CHMP opinion will now be submitted to the European Commission (EC) for review, with a final decision expected within the next two months. Piqray is an alpha-specific PI3K kinase inhibitor that has, to date, been approved in the United States and 12 other countries worldwide.

The CHMP’s opinion is based on the results of the Phase III SOLAR-1 trial. The data show that, compared withTumorIn patients with HR+/HER2- advanced breast cancer harboring PIK3CA mutations, treatment with Piqray plus fulvestrant significantly doubled progression-free survival (PFS) compared with fulvestrant alone (median PFS: 11.0 months vs. 5.7 months).

Principal Investigator of the SOLAR-1 Trial, Gustave Roussy Institute (IGR)TumorProfessor Fabrice André, MD, stated: “PIK3CA is the most commonly mutated gene in HR+/HER2- advanced breast cancer, affecting approximately 40% of patients. If approved, Piqray has the potential to transform the way we treat this cancer in Europe, providing physicians with a clear therapeutic option for patients with PIK3CA-mutated breast cancer that can double their progression-free survival.”

Novartis TumorDr. Susanne Schaffert, President of the relevant division, stated: “We are excited by today’s CHMP opinion, which recommends the first and only treatment regimen for European patients with cancer harboring PIK3CA mutations. Piqray is another example of how we are reshaping cancer care, delivering new targeted therapies to patients with high unmet needs and helping them live longer without disease progression.”

Chemical Structure of Alpelisib (Image source: selleckchem.com)

SOLAR-1 was a randomized, double-blind, placebo-controlled Phase III study conducted in postmenopausal women and men with PIK3CA-mutated, HR+/HER2− advanced or metastatic breast cancer who had experienced disease progression during or after treatment with an aromatase inhibitor (with or without a CDK4/6 inhibitor), to evaluate the efficacy and safety of Piqray in combination with fulvestrant.

A total of 572 patients were randomized in this study, based onTumorTissue assessment results were used to assign patients to either the PIK3CA-mutant cohort (n=341) or the PIK3CA non-mutant cohort (n=231). Within each cohort, patients were randomized in a 1:1 ratio to receive either Piqray (300 mg once daily) plus fulvestrant (500 mg, administered on a 28-day cycle, with an additional loading dose on Day 15 of Cycle 1) or placebo plus fulvestrant. Stratification was based on the presence of visceral metastases or prior CDK4/6 inhibitor therapy. The primary endpoint was progression-free survival (PFS) in patients with PIK3CA mutations, assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST version 1.1). Secondary endpoints included, but were not limited to, overall survival (OS), objective response rate (ORR), clinical benefit rate, health-related quality of life, efficacy in the PIK3CA non-mutant cohort, safety, and tolerability.

The results demonstrated that the study met its primary endpoint: in patients with PIK3CA-mutated, HR+/HER2- advanced breast cancer, treatment with Piqray in combination with fulvestrant nearly doubled progression-free survival (PFS) compared with fulvestrant alone (median PFS: 11.0 months vs. 5.7 months), and significantly reduced the risk of disease progression or death by 35% (HR=0.65, 95% CI: 0.50–0.85; p<0.001). In terms of overall response rate (ORR), the Piqray plus fulvestrant group achieved more than twice the ORR of the fulvestrant monotherapy group (36% vs. 16%). Subgroup analysis of PFS showed consistent efficacy of Piqray regardless of the presence of lung or liver metastases. In patients without PIK3CA mutations, the improvement in PFS with the combination of Piqray and fulvestrant was not significant.

In terms of safety, most adverse events in this study were mild to moderate and generally manageable through dose adjustments and medical management. The most common Grade 3/4 adverse events (≥7%) included hyperglycemia (39.1%), rash (19.4%), elevated gamma-glutamyl transferase (12.0%), lymphopenia (9.2%), diarrhea (7.0%), and elevated lipase (7.0%). No patients developedDiabetes. Currently, the SOLAR-1 study is still ongoing to evaluate overall survival (OS) and other secondary endpoints. (Bioon.com)

Original Source: Novartis Piqray® receives positive CHMP opinion to treat HR+/HER2- advanced breast cancer with a PIK3CA mutation