Novartis: Phase III study of Afinitor® shows significant extension of progression-free survival in advanced gastrointestinal or lung neuroendocrine tumors

• Study in patients with advanced nonfunctional neuroendocrine tumors (NET) of gastrointestinal (GI) or lung origin met primary endpoint[1]
• Full results will be submitted for presentation at a major medical meeting; worldwide regulatory filings are planned for 2015
• Afinitor is already approved in more than 95 countries for patients with advanced pancreatic NET, a rare form of cancer[1],[2],[3]

BASEL, 21-5-2015 — /EuropaWire/ — Novartis announced today that the Phase III study of Afinitor® (everolimus) tablets plus best supportive care in patients with advanced nonfunctional neuroendocrine tumors (NET) of gastrointestinal (GI) or lung origin met its primary endpoint: significant extension of progression-free survival (PFS) compared to placebo plus best supportive care[1]. The RADIANT-4 study is part of one of the largest clinical trial programs in NET[1].

NET are a rare type of cancer that originate in neuroendocrine cells found throughout the body, and are most often found in the GI tract, lungs or pancreas[4]. NET can be functional or nonfunctional: functional NET produce symptoms caused by the secretion of hormones and other substances; nonfunctional NET do not secrete hormones, and may only produce symptoms caused by the tumor’s growth, such as intestinal blockage, pain and bleeding[5],[6],[7]. At time of diagnosis, up to 44% of patients with GI NET and 28% of patients with lung NET have advanced disease, meaning the cancer has spread to other parts of the body and is more difficult to treat[2],[3],[4]. There are limited treatment options for patients with advanced GI or lung NET[4].

“We look forward to presenting the findings from the RADIANT-4 trial of everolimus, which has the potential to become an important treatment option for patients with advanced nonfunctional GI or lung NET,” said Alessandro Riva, MD, Global Head, Novartis Oncology Development and Medical Affairs. “The results will serve as the basis of planned worldwide regulatory filings for everolimus in these two types of NET, bringing us closer to our goal of offering Afinitor for these patients.”

Full results from the RADIANT-4 study will be submitted to a major medical meeting. Worldwide regulatory filings are planned for 2015.

About RADIANT-4
RADIANT-4 is a Phase III prospective, double-blind, randomized, parallel group, placebo-controlled, multicenter study. The trial examined the efficacy and safety of everolimus plus best supportive care versus placebo plus best supportive care in 302 patients with well differentiated advanced NET of GI or lung origin, and no history or active symptoms of carcinoid syndrome, who had documented disease progression within the previous 6 months. Patients were randomized 2:1 to receive either daily everolimus 10 mg or daily placebo orally.

The primary endpoint of RADIANT-4 was PFS. Secondary endpoints included safety, objective response rate and overall survival.

About Afinitor® (everolimus) tablets
Afinitor® (everolimus) is approved in more than 95 countries, including the United States and throughout the European Union, for locally advanced, metastatic or unresectable progressive neuroendocrine tumors of pancreatic origin. It is also approved in 119 countries including the United States and European Union for advanced renal cell carcinoma following progression on or after vascular endothelial growth factor (VEGF)-targeted therapy.

Afinitor is approved in the European Union for the treatment of hormone receptor-positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced breast cancer, in combination with exemestane, in postmenopausal women without symptomatic visceral disease after recurrence or progression following a non-steroidal aromatase inhibitor (NSAI). In the United States, Afinitor is approved for the treatment of postmenopausal women with advanced hormone receptor-positive, HER2 negative (advanced HR+/HER2-) breast cancer in combination with exemestane after failure of treatment with letrozole or anastrozole.

Everolimus is also available from Novartis for use in certain non-oncology patient populations under the brand names Afinitor® or Votubia®, Certican® and Zortress®and is exclusively licensed to Abbott and sublicensed to Boston Scientific for use in drug-eluting stents.

Indications vary by country and not all indications are available in every country. The safety and efficacy profile of everolimus has not yet been established outside the approved indications. Because of the uncertainty of clinical trials, there is no guarantee that everolimus will become commercially available for additional indications anywhere else in the world.

Important Safety Information about Afinitor® (everolimus) tablets
Afinitor/Votubia can cause serious side effects including lung or breathing problems, infections (including sepsis), and kidney failure, which can lead to death. Patients taking concomitant angiotensin-converting enzyme (ACE) inhibitors may be at an increased risk for angioedema. Mouth ulcers and mouth sores are common side effects. Afinitor/Votubia can affect blood cell counts, kidney and liver function, and blood sugar, cholesterol, and triglyceride levels. Afinitor/Votubia may cause fetal harm in pregnant women. Highly effective contraception is recommended for women of child-bearing potential while receiving Afinitor/Votubia and for up to eight weeks after ending treatment. Women taking Afinitor/Votubia should not breast feed. Fertility in women and men may be affected by treatment with Afinitor/Votubia.

The most common adverse drug reactions (incidence >=10 percent) are mouth ulcers, skin rash, feeling tired or weak, diarrhea, absence of menstrual periods, infections (including upper respiratory tract infection, sore throat and runny nose, sinusitis, and pneumonia), nausea, decreased appetite, low level of red blood cells, high levels of cholesterol, abnormal taste, acne, irregular menstrual periods, inflammation of lung tissue, high level of blood sugar, weight loss, itching, swelling of extremities or other parts of the body, nose bleeds, and headache. The most common Grade 3-4 adverse drug reactions (incidence >=2 percent) are mouth ulcers, absence of menstrual periods, low level of red blood cells, infections (including pneumonia), high level of blood sugar, feeling tired or weak, low white blood cells, inflammation of lung tissue, diarrhea, and spontaneous bleeding or bruising. Cases of hepatitis B reactivation, blood clots in the lung or legs, and pneumocystis jirovecii pneumonia (PJP) have been reported. Abnormalities were observed in hematology and clinical chemistry laboratory tests.

Disclaimer
The foregoing release contains forward-looking statements that can be identified by words such as “will,” “planned,” “can,” “look forward,” “potential,” “goal,” “plan,” “yet,” or similar terms, or by express or implied discussions regarding potential new indications or labeling for Afinitor, or regarding potential future revenues from Afinitor. 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 Afinitor 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 Afinitor will be commercially successful in the future. In particular, management’s expectations regarding Afinitor 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; global trends toward health care cost containment, including ongoing pricing pressures; unexpected manufacturing 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 2014, the Group achieved net sales of USD 58.0 billion, while R&D throughout the Group amounted to approximately USD 9.9 billion (USD 9.6 billion excluding impairment and amortization charges). Novartis Group companies employ approximately 120,000 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] National Library of Medicine and the National Institutes of Health. Pancreatic islet cell tumor. Available at http://www.nlm.nih.gov/medlineplus/ency/article/000393.htm. Accessed May 2015.
[3] Halfdanarson, et al. Pancreatic neuroendocrine tumors (PNETs): incidence, prognosis and recent trend toward improved survival. Annals of Onc. 2008; 19: 1727-1733.
[4] Yao, et al. One Hundred Years After “Carcinoid:” Epidemiology of and Prognostic Factors for Neuroendocrine Tumors in 35,825 Cases in the United States. J Clin Oncol. 2008; 26: 3063-72.
[5] Akerstrom, et al. Timing and extent of surgery in symptomatic and asymptomatic neuroendocrine tumors of the pancreas in MEN 1. Langenbecks Arch Surg. 2002; 386:558-69.
[6] Modlin, et al. Priorities for Improving the Management of Gasteroenteropancreatic Neuroendocrine Tumors. J Natl Cancer Inst 2008;100: 1282-1289.
[7] Oberg K, Kvols L, Caplin M, et al. Consensus report on the use of somatostatin analogs for the management of neuroendocrine tumors of the gastroenteropancreatic system. Ann Oncol. 2004: 966-976.

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