The Phase III NATALEE Trial of Novartis Kisqali Meets Primary Endpoint at Interim Analysis, Proving Significant Clinical Benefits for a Wide Range of

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Novartis meets primary goal in Phase III NATALEE trial for Kisqali®, showcasing significant benefits for various groups of early breast cancer patients.

March 27, 2023 | 1:16 in the morning Eastern Daylight Time

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Novartis has announced encouraging news from a study evaluating Kisqali® (ribociclib) in combination with endocrine therapy for patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative early breast cancer. The trial, known as NATALEE, has been stopped early due to positive interim results showing a significant reduction in the risk of disease recurrence for patients receiving Kisqali plus endocrine therapy compared to those on standard adjuvant ET alone. This benefit was consistent among patients with stage II and stage III EBC, regardless of nodal status. The Independent Data Monitoring Committee made the recommendation to halt the trial early based on the achievement of the primary endpoint of invasive disease-free survival.

According to Dennis J. Slamon, MD, who is the Director of Clinical/Translational Research at the University of California, Los Angeles Jonsson Comprehensive Cancer Center and the Chairman and Executive Director of Translational Research In Oncology (TRIO) and NATALEE trial lead investigator, breast cancer patients are usually diagnosed and treated early with the aim of curing the disease. However, the risk of cancer returning, often as metastatic disease, reaches its peak within three years after the diagnosis. Unfortunately, it never completely goes away. This creates a critical need for new treatment options that can help patients remain cancer-free while maintaining their quality of life. The NATALEE trial was designed with these unmet needs in mind. It involved giving patients ribociclib for three years plus ET. The trial has met its primary endpoint, which is extremely encouraging news.

According to the guidelines of the NATALEE study protocol, patients will be monitored over time to assess their long-term progress, which includes their survival rates.

"Our aim to broaden the reach of Kisqali to patients with early stages of breast cancer is being achieved with the encouraging outcomes of NATALEE. This successful treatment has already helped many with HR+/HER2- metastatic breast cancer and now we are hopeful to extend its benefits further. These findings could revolutionize the way patients at risk of recurrence, including those with no nodal involvement, are treated, especially since there are limited options available that can be tolerated well. We are currently preparing submissions to health authorities worldwide in the hope of bringing Kisqali to a greater number of individuals diagnosed with breast cancer." remarked Dr. Shreeram Aradhye, the Global Drug Development and Chief Medical Officer at Novartis.

The discoveries add to Kisqali's successful track record in treating metastatic breast cancer (MBC), as evidenced by positive results in three Phase III trials3-14 while maintaining or enhancing quality of life. The National Comprehensive Cancer Network (NCCN) updated their clinical practice guidelines in January 2023, endorsing ribociclib (Kisqali) as the sole preferred CDK4/6 inhibitor in combination with an aromatase inhibitor (AI) for initial therapy of HR+/HER2- MBC patients, earning a Category 1 rating.

NATALEE is a global trial that is being conducted in partnership with Translational Research in Oncology (TRIO). The trial is Phase III and multi-center and it aims to assess the efficacy and safety of Kisqali with ET versus ET alone in patients who have HR+/HER2- EBC. The primary endpoint of the trial is iDFS which is defined by STEEP criteria. Other secondary endpoints include quality of life, safety, and overall survival. iDFS is a composite endpoint that covers locoregional relapse, ipsilateral and contralateral invasive breast cancer, distant recurrence, and types of new cancer events or death from any cause. In the trial, 5,100 adult patients with HR+/HER2- EBC from 20 countries were randomized, including patients with stage IIA (selected patients), IIB or III, regardless of nodal involvement. The trial looked into a lower starting dose of Kisqali (400 mg) to reduce disruptions to patient quality of life while maintaining efficacy. This dose is lower than the dose approved for treatment in metastatic breast cancer (600 mg).

Most of the patients diagnosed with breast cancer have early breast cancer. It is estimated that around 30-60% of people with HR+/HER2- stage II and III early breast cancer who undergo endocrine therapy (ET) are still at risk of breast cancer recurrence. The chances of recurrence are highest in the first three years after diagnosis, and the risk continues for several decades. Unfortunately, there are limited targeted treatments available for these patients, and chemotherapy and ET remain the standard options.

The drug Kisqali® (ribociclib) has shown to be beneficial for overall patient survival while maintaining or improving the quality of life in three Phase III studies. The medical community recently updated the NCCN Guidelines®, recommending Kisqali as the only preferred CDK4/6 inhibitor for first-line treatment of patients with HR+/HER2- MBC when used in conjunction with an AI. Furthermore, Kisqali has received the highest rating among all CDK4/6 inhibitors on the ESMO Magnitude of Clinical Benefit Scale. This drug has been approved in 99 countries worldwide, including the US by the FDA and the European Commission. In the United States, Kisqali is authorized for the treatment of adult patients with HR+/HER2- advanced or metastatic breast cancer, while in the EU, it is approved for women with HR+/HER2- advanced or metastatic breast cancer.

Novartis is dedicated to further researching Kisqali's impact on breast cancer. Partnering with SOLTI, Novartis is involved in the HARMONIA study, which explores how Kisqali may alter tumor biology and lead to a stronger response to ET versus Ibrance for patients with metastatic HR+/HER2-, HER2-enriched subtype20. Akershus University Hospital in Norway is also collaborating with Novartis on the NEOLETRIB trial, a Phase II study analyzing the impact of Kisqali in HR+/HER2- EBC to uncover any unique mechanisms of action21. Novartis intends to expand on the knowledge gained from NATALEE in the ADJUVANT WIDER trial, which is an open-label Phase IIIb study assessing Kisqali plus ET among HR+/HER2- patients with stage II and III EBC, moving closer towards testing in a real-world population.

Kisqali was created by Novartis Institutes for BioMedical Research (NIBR) through a partnership with Astex Pharmaceuticals.

It is recommended that you refer to the complete prescribing information for Kisqali which can be found at the website www.Kisqali.com.

The following statement contains optimistic language regarding potential future development and profits for the drug Kisqali when used in conjunction with hormone therapy. However, readers should be aware that these statements are speculative and may not necessarily come to fruition due to various risks and uncertainties. These uncertainties could include issues in research and development, regulatory complications, difficulties with intellectual property protection, and other factors that could impact the success of the drug. Additionally, political, economic, and health-related factors may also play a role in the drug's success. Novartis AG assumes no responsibility to update any statements made within this release in the future.

Novartis is a company that is dedicated to improving the quality and length of people's lives through innovative medicine. They are working hard to address the most pressing health issues facing society by developing new drugs and finding ways to make them more accessible to those in need. Novartis is a global leader in research and development and invests heavily in this area. They have a diverse workforce of over 106,000 people from all over the world who are committed to making Novartis' products available to as many people as possible. If you want to learn more about Novartis and their important work, visit their website at https://www.novartis.com.

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