The FDA approved Novartis’s Kisqali® (ribociclib; formerly LEE011) combined with an aromatase inhibitor as a first-line, endocrine-based therapy for treating postmenopausal women with hormone receptor-positive (HR+), HER2– advanced or metastatic breast cancer. The selective cyclin-dependent kinase (CDK4/6) inhibitor was discovered through a research collaboration with Astex Pharmaceuticals.
FDA approval of Kisqali was based on data from the Phase III MONALEESA-2 study, which showed that treatment using Kisqali plus the aromatase inhibitor letrozole reduced the risk of disease progression or death by 44% compared with letrozole therapy alone.
The study met its primary endpoint at interim analysis. Subsequent analyses after additional follow-up also showed that median progression-free survival was 25.3 months for patients receiving Kisqali plus letrozole, compared with 16.0 months for those given letrozole alone.
More than 53% of patients with measurable disease who took Kisqali plus letrozole achieved a 30% or greater reduction in tumor size. “This is a significant result for women with this serious form of breast cancer,” said Gabriel N. Hortobagyi, M.D., professor of medicine, department of breast medical oncology at The University of Texas MD Anderson Cancer Center and MONALEESA-2 principal investigator. “These results affirm that combination therapy with a CDK4/6 inhibitor like ribociclib and an aromatase inhibitor should be a new standard of care for initial treatment of HR+ advanced breast cancer.”
“Kisqali is emblematic of the innovation that Novartis continues to bring forward for people with HR+/HER2– metastatic breast cancer,” added Bruno Strigini, CEO, Novartis Oncology. “We at Novartis are proud of the comprehensive clinical program for Kisqali that has led to today's approval and the new hope this medicine represents for patients and their families.”
Ongoing Kisqali clinical trials include the MONALEESA-3 study, which is evaluating Kisqali combined with fulvestrant in postmenopausal women with HR+/HER2– advanced breast cancer who have received either no or just one prior endocrine therapy. MONALEESA-7 is evaluating Kisqali combined with endocrine therapy and goserelin in premenopausal women with HR+/HER2– advanced breast cancer who have not received prior endocrine therapy.
Astex and Novartis established their collaboration to discover cell cycle inhibitors back in 2005. FDA approval of Kisqali triggers a milestone payment to Astex. The U.K.- and U.S.-based company will also receive milestones on regulatory filings for Kisqali in Europe and Japan, plus royalties on global sales of the drug. Harren Jhoti, president and CEO of Astex, U.K., said, “We’re committed to the fight against cancer and so we are absolutely delighted that Novartis has received this first approval of a cancer drug arising from our productive collaboration. This milestone further validates the power of our Pyramid™ platform and the excellence of our science.”
Astex is exploiting its Pyramid™ fragment-based drug discovery platform to develop a proprietary and partnered pipeline of drugs against cancer and central nervous system disorders. The firm’s lead in-house candidate guadecitabine (SGI-110) is a DNA hypomethylating agent, which is being evaluated in the Phase III ASTRAL-1 study in treatment-naïve patients with acute myeloid leukemia (AML) who are not suitable for intensive remission induction chemotherapy. Astex’s most recent collaboration, signed in April 2016 with Genentech, aims to evaluate guadecitabine combined with Genentech’s investigational anti-programmed death-ligand 1 (PD-L1) monoclonal antibody atezolizumab for treating AML. Astex was acquired by Otsuka Pharmaceutical, for $866 million, in 2013.
Pfizer’s CDK4/6 inhibitor Ibrance® (palbociclib) was approved by the FDA in 2015 as combination therapy with letrozole for the HR+/HER2– metastatic breast cancer indication. Approval for the drug in combination with fulvestrant was granted in February 2016. Eli Lilly’s CDK4/6 inhibitor abemaciclib, meanwhile, is being evaluated in the Phase II and Phase III MONARCH trials.