Novartis gains FDA approval for Afinitor®

NovartisNovartis announced that the US Food and Drug Administration (FDA) approved Afinitor® (everolimus) tablets for the treatment of progressive neuroendocrine tumors of pancreatic origin (PNET) in patients with unresectable, locally advanced or metastatic disease[4]. This marks the first approval of a treatment for this patient population in the US in nearly 30 years[5].

The approval was based on Phase III data from the RADIANT-3 (RAD001 In Advanced Neuroendocrine Tumors) trial showing treatment with Afinitor more than doubled the time without tumor growth (median 4.6 to 11.0 months) and reduced the risk of cancer progression by 65% when compared with placebo in patients with advanced pancreatic NET (hazard ratio=0.35 [95% confidence interval (CI), 0.27 to 0.45]; p<0.001). A consistent improvement in progression-free survival was seen with Afinitor in all patient subgroups[1]. The FDA determined that the safety and effectiveness of Afinitor in the treatment of patients with carcinoid tumors have not been established[4].

"The FDA approval of Afinitor represents an important step forward for patients with advanced pancreatic NET," said James Yao, MD, Associate Professor of Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas. "Patients will now have access to a treatment that has been shown to significantly delay tumor growth and reduce the risk of disease progression."

Approximately 60% of pancreatic NET patients are diagnosed with advanced disease[2]. This means that the cancer has already spread to other parts of the body, and is considered aggressive and difficult to treat[3]. The five-year survival rate for these patients is 27%[6].

"With this approval, US physicians can now offer their patients with progressive pancreatic NET a new treatment helping to fulfill a critical unmet need," said Hervé Hoppenot, President, Novartis Oncology. "This is the third indication for Afinitor in the US in just over two years, providing further evidence that inhibiting mTOR plays an important role in treating multiple tumor types."

Afinitor targets mTOR, a protein that acts as an important regulator of tumor cell division, blood vessel growth and cell metabolism[7]. Preclinical and clinical data have established the role of mTOR in the development and progression of several types of tumors, including advanced pancreatic NET[1],[7]

Novartis has submitted marketing applications for everolimus for the treatment of patients with advanced NET of gastrointestinal, lung or pancreatic origin to the European Medicines Agency (EMA) and the Swiss Agency for Therapeutic Products (Swissmedic), and additional regulatory submissions are being reviewed by health authorities worldwide.

About neuroendocrine tumors of pancreatic origin (pancreatic NET)
Neuroendocrine tumors arise from cells that can produce and secrete a variety of hormones that regulate bodily functions[8]. These tumors can occur anywhere in the body; however, most are found in the pancreas (pancreatic NET), gastrointestinal tract or lungs (carcinoid tumors)[6],[9]. Pancreatic NET, also known as islet cell tumors, is a rare type of cancer different from pancreatic exocrine cancer, which is generally referred to as pancreatic cancer[3],[10]. There have been limited treatment options for patients with pancreatic NET[2].

About RADIANT-3
RADIANT-3 is a Phase III prospective, double-blind, randomized, parallel group, placebo-controlled, multicenter study. The trial examined the efficacy and safety of Afinitor plus best supportive care (BSC) versus placebo plus BSC in 410 patients with advanced, low- or intermediate-grade pancreatic NET. Patients who met the study entry criteria were randomized 1:1 to receive either Afinitor 10 mg once-daily (n=207) or daily placebo (n=203) orally, both in conjunction with BSC[1].

The primary endpoint of RADIANT-3 is progression-free survival. Secondary endpoints include safety, objective response rate (confirmed according to RECIST), duration of response and overall survival[1].

About Afinitor (everolimus)
Afinitor® (everolimus) tablets is approved in the US for the treatment of progressive neuroendocrine tumors of pancreatic origin in patients with unresectable, locally advanced or metastatic disease. The FDA determined that the safety and effectiveness of Afinitor in the treatment of patients with carcinoid tumors have not been established.

Afinitor is approved in the European Union (EU) for the treatment of patients with advanced renal cell carcinoma (RCC) whose disease has progressed on or after treatment with vascular endothelial growth factor (VEGF)-targeted therapy and also in the US for the treatment of patients with advanced RCC after failure of treatment with sunitinib or sorafenib.

Afinitor is also approved in the US to treat patients with subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis who require therapeutic intervention but are not candidates for curative surgical resection. The effectiveness of Afinitor is based on an analysis of change in SEGA volume. Clinical benefit such as improvement in disease-related symptoms or increase in overall survival has not been shown. Novartis has submitted marketing applications for everolimus for this use to the European Medicines Agency (EMA) and the Swiss Agency for Therapeutic Products (Swissmedic), and additional regulatory submissions are under way worldwide.

In the EU, everolimus is available in different dosage strengths for the non-oncology patient population under the trade name Certican® for the prevention of organ rejection in heart and kidney transplant recipients. In the US, everolimus is available in different dosage strengths under the trade name Zortress® for the prophylaxis of organ rejection in adult patients at low-moderate immunologic risk receiving a kidney transplant.

Everolimus is exclusively licensed to Abbott and sublicensed to Boston Scientific for use in drug-eluting stents.

Not all indications are available in every country. As an investigational compound the safety and efficacy profile of everolimus has not yet been established in all countries in pancreatic or any other type of NET. Access to everolimus outside of the approved indications has been carefully controlled and monitored in clinical trials designed to better understand the potential benefits and risks of the compound. Because of the uncertainty of clinical trials, there is no guarantee that everolimus will become commercially available for pancreatic or any other type of NET, or additional indications anywhere else in the world.

About Novartis
Novartis provides healthcare solutions that address the evolving needs of patients and societies. Focused solely on healthcare, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, eye care, cost-saving generic pharmaceuticals, consumer health products, preventive vaccines and diagnostic tools. Novartis is the only company with leading positions in these areas. In 2010, the Group's continuing operations achieved net sales of USD 50.6 billion, while approximately USD 9.1 billion (USD 8.1 billion excluding impairment and amortization charges) was invested in R&D throughout the Group. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 119,000 full-time-equivalent associates and operate in more than 140 countries around the world.

1. Yao, et al. Everolimus for Advanced Pancreatic Neuroendocrine Tumors. New Eng J Med 2011;364:514-23.
2. Halfdanarson, et al. Pancreatic neuroendocrine tumors (PNETs): incidence, prognosis and recent trend toward improved survival. Annals of Onc 19: 1727-1733, 2008.
3. 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 April 2011.
4. Novartis data on file. http://www.pharma.us.novartis.com/product/pi/pdf/afinitor.pdf. Accessed May 2011.
5. US Food and Drug Administration. Drug Details. ZANOSAR. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails. Accessed April 2011.
6. Yao, et al. One Hundred Years After "Carcinoid:" Epidemiology of and Prognostic Factors for Neuroendocrine Tumors in 35,825 Cases in the United States. Journal of Clinical Oncology. June 20 2009; vol. 26, number 18.
7. Motzer, et. al. Phase 3 Trial of Everolimus for Metastatic Renal Cell Carcinoma. Cancer 2010 Sep; 116(18):4256-4265.
8. National Library of Medicine and the National Institutes of Health. Neuroendocrine Tumor. Available at http://www.cancer.gov/dictionary/?CdrID=44904. Accessed April 2011.
9. American Cancer Society Detailed Guides. Gastrointestinal Carcinoid Tumors. Available at http://www.cancer.org/acs/groups/cid/documents/webcontent/003102-pdf.pdf. Accessed April 2011.
10. American Cancer Society Detailed Guides. Pancreatic Cancer. Available at http://www.cancer.org/acs/groups/cid/documents/webcontent/003131-pdf.pdf. Accessed April 2011.

Most Popular Now

Pfizer announces positive top-line results from Ph…

Pfizer Inc. (NYSE: PFE) today announced positive top-line results from the Phase 3 BENEGENE-2 study (NCT03861273) evaluating fidanacogene elaparvovec, an investigational ...

Time-restricted eating reshapes gene expression th…

Numerous studies have shown health benefits of time-restricted eating including increase in life span in laboratory studies, making practices like intermittent fasting a ...

Incurable liver disease may prove curable

Research led by Associate Professor Duc Dong, Ph.D., has shown for the first time that the effects of Alagille syndrome, an incurable genetic disorder that affects the li...

Scientists develop a cancer vaccine to simultaneou…

Scientists are harnessing a new way to turn cancer cells into potent, anti-cancer agents. In the latest work from the lab of Khalid Shah, MS, PhD, at Brigham and Women’s ...

AstraZeneca to acquire CinCor Pharma to strengthen…

AstraZeneca has entered into a definitive agreement to acquire CinCor Pharma, Inc. (CinCor), a US-based clinical-stage biopharmaceutical company, focused on developing no...

COVID-19 vaccines, prior infection reduce transmis…

Vaccination and boosting, especially when recent, helped to limit the spread of COVID-19 in California prisons during the first Omicron wave, according to an analysis by ...

NextPoint Therapeutics announces $80 million Serie…

NextPoint Therapeutics, a biotechnology company developing a new world of precision immuno-oncology, announced today that it raised $80 million in Series B financing co-l...

Enzyme that protects against viruses could fuel ca…

An enzyme that defends human cells against viruses can help drive cancer evolution towards greater malignancy by causing myriad mutations in cancer cells, according to a ...

Nanotechnology may improve gene therapy for blindn…

Using nanotechnology that enabled mRNA-based COVID-19 vaccines, a new approach to gene therapy may improve how physicians treat inherited forms of blindness. A collabo...

Bayer to accelerate drug discovery with Google Clo…

Bayer AG and Google Cloud announced a collaboration to drive early drug discovery that will apply Google Cloud's Tensor Processing Units (TPUs), which are custom-develope...

Study identifies potential new approach for treati…

Targeting iron metabolism in immune system cells may offer a new approach for treating systemic lupus erythematosus (SLE) - the most common form of the chronic autoimmune...

Acquisition of Neogene Therapeutics completed

AstraZeneca has completed the acquisition of Neogene Therapeutics Inc. (Neogene), a global clinical-stage biotechnology company pioneering the discovery, development and ...