MONALEESA-2 trial of Novartis' LEE011 (ribociclib) stopped due to positive efficacy results at interim analysis in HR+/HER2- advanced breast cancer

• Independent Data Monitoring Committee recommends stopping the trial early as it met the primary endpoint, significantly extending progression-free survival (PFS) compared to letrozole alone, at pre-planned interim analysis[1]
  
  
• LEE011 (ribociclib), a CDK4/6 inhibitor, in combination with letrozole, showed clinically meaningful improvement in PFS in postmenopausal women who had received no prior therapy for advanced breast cancer[1]
  
  
• Full results will be presented at an upcoming medical congress; Novartis will initiate discussions with regulatory authorities worldwide

Basel, May 18, 2016 - Novartis announced today that the MONALEESA-2 independent Data Monitoring Committee recommended stopping the trial early as results of a pre-planned interim analysis showed the trial met the primary endpoint of clinically meaningful improvement in PFS[1]. MONALEESA-2 is a pivotal Phase III trial of LEE011 (ribociclib), a cyclin dependent kinase inhibitor (CDK4/6), in combination with letrozole, compared to letrozole alone in postmenopausal women who had received no prior therapy for their hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced breast cancer[1].

"We are excited that these results validate our belief that LEE011 in combination with letrozole can be a beneficial treatment option for women diagnosed with HR+/HER2- advanced breast cancer," said Alessandro Riva, Global Head, Oncology Development and Medical Affairs, Novartis Oncology. "Novartis is dedicated to continuing to discover and develop innovative targeted therapies that help improve and extend the lives of women living with this disease."

As part of the company's ongoing commitment to addressing the needs of patients living with advanced breast cancer, Novartis will be evaluating possible expanded access programs in some regions to help ensure women who may benefit from LEE011 have access to it.

The adverse events observed with LEE011 in combination with letrozole in MONALEESA-2 were generally consistent with their respective known adverse event profiles[1].

The MONALEESA-2 trial will continue to assess overall survival data. Detailed efficacy and safety data will be submitted for presentation at a major medical congress and Novartis will begin discussions with global health authorities about regulatory filings. 

About MONALEESA-2
MONALEESA-2 (Mammary ONcology Assessment of LEE011's Efficacy and SAfety-2) is a Phase III randomized, double blind, placebo controlled, multicenter global registration trial to evaluate the safety and efficacy of LEE011 in combination with letrozole compared to letrozole alone in postmenopausal women with HR+/HER2- advanced breast cancer who received no prior therapy for their advanced breast cancer[1].

The trial was conducted at 294 clinical trial sites globally and randomized 668 patients in a 1:1 ratio stratified by the presence of liver and/or lung metastases[1]. Patients received LEE011 600 mg/daily (three weeks on and one week off), or placebo, in combination with letrozole 2.5 mg/daily per the approved label[1].

The primary endpoint of the trial was PFS[1]. Secondary endpoints included: overall survival, overall response rate, clinical benefit rate, health-related quality of life, safety and tolerability[1].

About LEE011 (ribociclib)
LEE011 (ribociclib) is a cyclin dependent kinase inhibitor (CDKi), a new 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 in a cell, can enable cancer cells to grow and divide too quickly.

LEE011 has been studied in non-clinical models and is currently being evaluated in combination with additional endocrine agents as part of the MONALEESA clinical trial program. LEE011 is not approved for any indication in any market at this time.

The MONALEESA-3 trial is evaluating LEE011 in combination with fulvestrant compared to fulvestrant alone in men and post-menopausal women with HR+/HER2- advanced breast cancer who have received no or a maximum of one prior endocrine therapy. The MONALEESA-7 trial is investigating LEE011 in combination with endocrine therapy and goserelin compared to endocrine therapy and goserelin alone in pre-menopausal women with HR+/HER2- advanced breast cancer who have not previously received endocrine therapy. Both Phase III programs, MONALEESA-3 and MONALEESA-7 are recruiting patients worldwide.

LEE011 was developed by Novartis Institutes for BioMedical Research (NIBR) under a research collaboration with Astex Pharmaceuticals.

About Novartis in advanced breast cancer
For more than 25 years, Novartis has been at the forefront of driving scientific advancements for breast cancer patients and improving clinical practice in partnership with the global community[1]. With one of the most diverse breast cancer pipelines and the largest number of breast cancer compounds in development, Novartis leads the industry in discovery of new therapies and combinations, especially in HR+ advanced breast cancer, the most common form of the disease[1].

About advanced breast cancer
Advanced breast cancer comprises metastatic breast cancer (stage IV) and locally advanced breast cancer (stage III)[2]. Metastatic breast cancer is the most serious form of the disease and occurs when the cancer has spread to other parts of the body, such as the brain, bones or liver[2]. Locally advanced breast cancer occurs when the cancer has spread to lymph nodes and/or other tissue in the area of the breast, but not to distant sites in the body[2].

HR+/HER2- advanced breast cancer is the most common type of advanced breast cancer, with an estimated 220,000 women diagnosed globally each year[3],[4]. HR+ advanced breast cancer is a group of cancers that express receptors for certain hormones, such as estrogen and progesterone[5]. Cancer cell growth can be driven by these hormones[5].

Disclaimer
The foregoing release contains forward-looking statements that can be identified by words such as "will," "pursue," "belief," "dedicated," "continuing," "commitment," "possible," "may," "to evaluate," "being evaluated," "is evaluating," "is investigating," "are recruiting," or similar terms, or by express or implied discussions regarding potential new indications or labeling for LEE011, or regarding potential future revenues from LEE011. You should not place undue reliance on these statements. Such forward-looking statements are based on the current beliefs and expectations of management regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that LEE011 will be submitted or approved for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that LEE011 will be commercially successful in the future. In particular, management's expectations regarding LEE011 could be affected by, among other things, the uncertainties inherent in research and development, including unexpected clinical trial results and additional analysis of existing clinical data; unexpected regulatory actions or delays or government regulation generally; the company's ability to obtain or maintain proprietary intellectual property protection; general economic and industry conditions; competition in general; global trends toward health care cost containment, including ongoing pricing pressures; unexpected manufacturing, safety or quality issues, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Novartis
Novartis provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, eye care and cost-saving generic pharmaceuticals. Novartis is the only global company with leading positions in these areas. In 2015, the Group achieved net sales of USD 49.4 billion, while R&D throughout the Group amounted to approximately USD 8.9 billion (USD 8.7 billion excluding impairment and amortization charges). Novartis Group companies employ approximately 118,000 full-time-equivalent associates. Novartis products are available in more than 180 countries around the world. For more information, please visit http://www.novartis.com.

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References
[1] Novartis Data on File.
[2] American Cancer Society. How do you determine the stage of breast cancer? Available at http://www.cancer.org/cancer/breastcancer/detailedguide/breast-cancer-staging. Accessed May 10, 2016.
[3] Dobrescu A, et al. Study of Estrogen Receptor and Progesterone Receptor Expression in Breast Ductal Carcinoma In Situ by Immunohistochemical Staining in ER/PgR-Negative Invasive Breast Cancer. International Scholarly Research Network. 2011;2011:1-5.
[4] Buckley N, et al. Breast Cancer. Decision Resources. March 2011:1-301.
[5] Redmond C. Breast Cancer Hormone Therapy Options. Available at http://christineredmond.suite101.com/breast-cancer-hormone-therapy-options-a197304. Accessed December 1, 2014.

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