In response to recent FDA guidelines which limit the nitrosamine content of drugs, Novartis has paused the enrollment of early breast cancer (eBC) patients in clinical trials of its blockbuster Kisqali (ribociclib).
“We are implementing manufacturing adjustments to ensure alignment with the latest regulatory standards in eBC by the end of Q2,” Novartis said in a brief, four-sentence release, adding that it expects the regulatory review of Kisqali in the indications to “proceed as planned.”
The halt does not affect patients on Kisqali in its approved indication, Novartis said. The FDA endorsed Kisqali in 2017 to treat hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2) advanced or metastatic breast cancer (mBC).
A company spokesperson declined to reveal what manufcturing tweaks are needed or how many trials are affected. Clinicaltrials.gov lists several eBC studies underway testing Kisqali.
In August of last year, the FDA issued guidance on the recommended acceptable limit for the intake of nitrosamine impurities. By August of 2025, drugmakers must ensure that their products that contain nitrosamines are in compliance with the guidelines. Some preliminary data suggest nitrosamines can cause cancer.
Nitrosamines are unintentional by-products found in a wide variety of goods such as cured meat, fish, dairy products, vegetables, cosmetics, tobacco and pharmaceutical products. They also are found in the air and water and their levels can increase in products during their manufacture and afterward as they degenerate in storage.
In August last year, the FDA finalized guidance on intake limits for nitrosamine impurities after companies including Phathom Pharmaceuticals faced commercial setbacks due to nitrosamine-related problems. Earlier this month, ARS Pharmaceutical responded to a CRL issued in September requesting completion of updated nitrosamine testing for its epinephrine nasal spray.
Four months ago at the San Antonio Breast Cancer Symposium, Novartis reported strong data from the NATALEE trial, showing that Kisqali plus an aromatase inhibitor after surgery reduced the risk of invasive disease occurrence or death by 25% in patients with early-stage HR+/HER2 breast cancer.
Last year, Kisqali was Novartis’ fifth best-selling drug, generating $2.1 billion. Novartis is trying to broaden the population of breast cancer patients eligible for Kisqali as it’s attempt to run down Eli Lilly’s market leader in the adjuvant setting, Verzenio, which generated sales of $3.9 billion in 2023.