The Committee for Medicinal Products for Human Use of the European Medicines Agency has adopted a positive opinion recommending an expanded indication for Kisqali (ribociclib), the CDK4/6 inhibitor with the largest body of first-line clinical trial evidence demonstrating consistent, superior and sustained efficacy compared to endocrine therapy alone.
The drug is sponsored by Novartis.
CHMP recommended Kisqali for the treatment of women with hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) locally advanced or metastatic breast cancer in combination with fulvestrant as initial endocrine-based therapy and in women who have received prior endocrine therapy. The positive opinion also recommended approval of Kisqali in combination with endocrine therapy and a luteinising hormone-release hormone agonist (LHRH) for pre- and perimenopausal women.
This positive CHMP opinion is based on data from the Phase III MONALEESA-7 and MONALEESA-3 trials. These trials demonstrated prolonged progression-free survival (PFS) for Kisqali-based regimens compared to endocrine therapy alone and showed improvements as early as eight weeks after start of treatment with Kisqali combination therapy.
In MONALEESA-7, Kisqali plus an aromatase inhibitor and goserelin nearly doubled the median PFS compared to an aromatase inhibitor and goserelin alone in pre- or perimenopausal women (27.5 months compared to 13.8 months; HR=0.569; 95% CI: 0.436-0.743)[3]. In MONALEESA-3, Kisqali plus fulvestrant demonstrated a median PFS of 20.5 months compared to 12.8 months for fulvestrant alone (HR=0.593; 95% CI: 0.480-0.732) across the overall population of first-line and second-line postmenopausal women. Across the two trials, the most common adverse reactions (incidence >=20%) were neutropenia, nausea, infections, fatigue, diarrhea, leukopenia, vomiting, alopecia, headache, constipation, rash and cough.
The European Commission will review the CHMP recommendation and usually delivers its final decision within two months. The decision will be applicable to all 28 European Union member states plus Iceland, Norway and Liechtenstein. Additional regulatory filings are underway with other health authorities worldwide.
Kisqali is a selective cyclin-dependent kinase inhibitor, a class of drugs that help slow the progression of cancer by inhibiting two proteins called cyclin-dependent kinase 4 and 6 (CDK4/6). These proteins, when over-activated, can enable cancer cells to grow and divide too quickly. Targeting CDK4/6 with enhanced precision may play a role in ensuring that cancer cells do not continue to replicate uncontrollably.
Kisqali was initially approved by FDA in March 2017 and by the European Commission in August 2017, as initial endocrine-based therapy for postmenopausal women with HR+/HER2- locally advanced or metastatic breast cancer in combination with an aromatase inhibitor based on findings from the pivotal MONALEESA-2 trial[12]. In July 2018, Kisqali was approved by the FDA for the treatment of pre-, peri- or postmenopausal women in the US, and indicated for use in combination with fulvestrant as both first- or second-line therapy in postmenopausal women.
The Oncologic Drugs Advisory Committee held its first session since President Trump’s inauguration, with a two-day, back-to-back marathon meeting, signaling a return to business at FDA after significant upheaval at the agency.
