On July 18, 2018, the FDA expanded the approval granted Novartis Pharmaceuticals Corporation to market Kisqali (ribociclib) in combination with an aromatase inhibitor for the initial endocrine-based treatment of pre/perimenopausal or postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. Aromatase inhibitors (AIs) are a class of drugs used in the treatment of breast cancer in postmenopausal women. The FDA also approved Kisqali in combination with fulvestrant for the treatment of postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer, as initial endocrine based therapy or following disease progression on endocrine therapy.
Kisqali was first approved in March 2017 for use with an AI to treat HR-positive, HER2-negative breast cancer only in post-menopausal women whose cancer was advanced or had spread to other parts of the body.
“The approval adds a new treatment choice for patients with breast cancer,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “We are committed to continuing to bring more treatment options to patients.”
Breast cancer is the most common form of cancer in the United States. The National Cancer Institute at the National Institutes of Health estimates approximately 266,120 women will be diagnosed with breast cancer this year and 40,920 will die of the disease. Approximately 72 percent of patients with breast cancer have tumors that are HR-positive and HER2-negative.
The efficacy of Kisqali in combination with an AI for pre/perimenopausal women was demonstrated in a clinical trial. All pre- or peri-menopausal patients in this study received ovarian suppression with goserelin, a hormone-based chemotherapy. The trial measured progression-free survival (PFS), which is generally the amount of time after the start of this treatment during which the cancer does not substantially grow and the patient is alive. PFS was longer for patients taking Kisqali plus an AI (median PFS of 27.5 months) compared to patients who received placebo plus an AI (median PFS of 13.8 months).
The efficacy of Kisqali in combination with fulvestrant in treating advanced or metastatic breast cancer was demonstrated in a clinical trial. The trial measured PFS, which was longer for patients taking Kisqali plus fulvestrant (median PFS of 20.5 months) compared to patients who received placebo plus fulvestrant (median PFS of 12.8 months).
The common side effects of Kisqali are infections, abnormally low count of a type of white blood cell (neutropenia), a reduction in the number of white cells in the blood (leukopenia), headache, cough, nausea, fatigue, diarrhea, vomiting, constipation, hair loss, and rash.
Warnings include the risk of a heart problem known as QT prolongation that can cause an abnormal heartbeat and may lead to death. Additional warnings include serious liver problems, low white blood cell counts that may result in infections that may be severe, and fetal harm.
This is the first approval that the FDA has granted as a part of two new pilot programs, Real-Time Oncology Review and a new structured templated Assessment Aid. Both programs aim to make the development and review of cancer drugs more efficient, while improving the FDA’s rigorous standard for evaluating efficacy and safety.
The first new pilot program, Real-Time Oncology Review, allows for the FDA to review much of the data earlier, after the clinical trial results become available and the database is locked, before the information is formally submitted to the FDA. This allows the FDA to begin its analysis of the data earlier and provide feedback to the sponsor on how they can most effectively analyze the data to answer key regulatory questions. Real-Time Oncology Review focuses on early submission of data that are the most relevant to assessing safety and effectiveness of the product. Then, when the sponsor submits the application to the FDA, the review team will already be familiar with the data and in a better position to conduct a more efficient, timely, and thorough review. With this real-time review, the FDA was able to start evaluating the clinical data from Kisqali as soon as the trial results became available, enabling the FDA to be ready to approve the new indication as soon as Novartis Pharmaceuticals Corporation filed a formal application to the FDA.
The second pilot program is a new structured templated Assessment Aid that the applicant uses to organize its submission into a structured format to facilitate the FDA’s review of the application. By using a structured template, the FDA is able to layer its assessment into the same file submitted by the sponsor, allowing this annotated application to serve as the document that contains the FDA review. This voluntary submission form provides for a more streamlined approach to reviewing data and illustrating the FDA’s analysis. It allows for drug reviewers to focus on the key benefit-risk and labeling issues rather than administrative issues.
“With this approval, we’ve demonstrated some of the benefits of the new programs that we’re piloting for our review of cancer drugs, to improve regulatory efficiency while enhancing the process for evaluating the data submitted to us. These new programs were designed to reduce some of the administrative issues that can add to the time and cost of the review process, including the staffing burdens on the FDA,” said FDA Commissioner Scott Gottlieb, M.D. “With today’s approval, the FDA used these new approaches to allow the review team to start analyzing data before the actual submission of the application and help guide the sponsor’s analysis of the top-line data to tease out the most relevant information. This enabled our approval less than one month after the June 28 submission date and several months ahead of the goal date.”
Currently the two pilot programs are being used for supplemental applications for already-approved cancer drugs and could later be expanded to original drugs and biologics.
See the FDA Announcement
See also Medical Risk Law Report: Drugs, Dosage, and Damage: Physician Liability for Prescribing or Administering Medication