Pfizer Inc. announced today that the U.S. Food and Drug Administration (FDA) has approved SUTENT? (sunitinib malate) as the first anti-VEGF therapy to treat progressive, well-differentiated pancreatic neuroendocrine tumors (NET) in patients with unresectable locally advanced or metastatic disease. Pancreatic NET is a rare cancer reported in two to four people per million annually worldwide.1,2

“We are delighted that SUTENT has been granted approval by the FDA as an effective treatment option for individuals with pancreatic NET. This approval represents the third disease indication for SUTENT, which was approved by the FDA in 2006 for treatment of patients with advanced kidney cancer and imatinib-resistant or intolerant gastrointestinal stromal tumor (GIST),” said Dr. Mace Rothenberg, senior vice president of Clinical Development and Medical Affairs, Pfizer Oncology Business Unit. “Pfizer is committed to improving the lives of those with cancer. This approval is good news for the physicians, patients and caregivers who have had limited treatment options for this rare and difficult-to-treat tumor.”

the FDA approval is based on data from the SUN 1111 pivotal Phase 3 trial that demonstrated SUTENT provided a clinically significant improvement in progression-free survival (PFS) compared to placebo (10.2 versus 5.4 months, p=0.000146) in this patient population.3 Treatment with SUTENT also yielded a statistically significant improvement in tumor response, with an objective response rate (ORR) of 9.3 percent (95% CI: 3.2, 15.4, p=0.0066). No objective responses were observed with placebo. in addition, while overall survival (OS) was not mature at the time of final analysis, nine deaths were observed in patients enrolled in the SUTENT arm versus 21 deaths in patients enrolled in the placebo arm.3,4

“This approval is welcome news for physicians who have struggled to find a treatment option that shows a substantial clinical benefit in treating advanced pancreatic NET,” said Dr. Eric Raymond, professor of medical oncology and head of University Department of Medical Oncology (Service Inter Hospitalier de Cancerologie) Bichat-Beaujon, Clichy, France and principal investigator of the SUN 1111 Phase 3 trial. “Pancreatic NET is a highly vascular tumor, and as the first anti-VEGF therapy approved for this disease, SUTENT represents a treatment that attacks a key component of tumor growth.”

About the SUN 1111 Trial

SUN 1111 was a multicenter, international, randomized, double-blind, placebo-controlled Phase 3 study (n=171) evaluating single-agent SUTENT in patients with unresectable pancreatic NET, characterized by cancer that could not be surgically removed. the primary endpoint was PFS. other endpoints included OS, ORR and safety. use of somatostatin analogs were allowed in the study.3

the approval of SUTENT in this patient population was based on FDA assessment of PFS observed in SUN 1111. Previously reported investigator-assessed data from the trial, published in the New England Journal of Medicine, showed SUTENT more than doubled median PFS compared with placebo (11.4 versus 5.5 months, p<0.0001), which was found to be consistent in a blinded, independent central review of scans from the study (12.6 versus 5.8 months, p=0.000015).4,5 in February 2009, the independent Data Monitoring Committee for the SUN 1111 trial recommended that randomization to the study be halted early in the interest of patient safety and based on the very strong likelihood that the study would meet its primary endpoint if continued to completion. This may have led to an overestimate of the magnitude of PFS effect.

SUTENT has been approved for advanced pancreatic NET in Europe and nine additional countries. SUTENT is also approved for both gastrointestinal stromal tumors (GIST) after disease progression on or intolerance to imatinib mesylate, and advanced renal cell carcinoma (RCC) in over 100 countries and has been studied in over 10,000 patients in clinical trials. to date, with more than five years of experience, more than 100,000 patients have been treated with SUTENT worldwide.

About Pancreatic Neuroendocrine Tumors (Pancreatic NET)

Pancreatic NET is different from pancreatic adenocarcinoma, which account for about 95 percent of all pancreatic cancers.6 Pancreatic NET is a member of a broad group of cancers called neuroendocrine tumors, which arise from hormone-producing cells of the body.7,8 while neuroendocrine tumors that develop in the pancreas are known as pancreatic NET, those that arise in other areas of the body, including the lungs and gastrointestinal tract, are known as carcinoids.7 Pancreatic NET, which are mostly well-differentiated,9 account for approximately 22-28 percent of all neuroendocrine tumors.10,11 nearly 90 percent of patients with pancreatic NET are initially diagnosed with locally advanced or metastatic disease (cancer that has spread to other organs).12 for patients with pancreatic NET that has metastasized, prognosis is poor, with a survival of only 1-3 years,13 similar to that seen with metastatic breast cancer or metastatic colon cancer.14,15

About SUTENT(?) (sunitinib malate)

SUTENT is an oral multi-kinase inhibitor that works by blocking multiple molecular targets implicated in the growth, proliferation and spread of cancer. Two important SUTENT targets, vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) are expressed by many types of solid tumors and are thought to play a crucial role in angiogenesis, the process by which tumors acquire blood vessels, oxygen and nutrients needed for growth. SUTENT also inhibits other targets important to tumor growth, including KIT, FLT3 and RET.

Important SUTENT(?) (sunitinib malate) Safety Information

Hepatotoxicity has been observed in clinical trials and post-marketing experience. This hepatotoxicity may be severe, and deaths have been reported. It is recommended to monitor liver function tests before initiation of treatment, during each cycle of treatment, and as clinically indicated. SUTENT should be interrupted for Grade 3 or 4 drug-related hepatic adverse events and discontinued if there is no resolution. SUTENT should not be restarted if patients subsequently experience severe changes in liver function tests or have other signs and symptoms of liver failure.

Women of child bearing age who are (or become) pregnant during therapy should be informed of the potential for fetal harm while on SUTENT.

Decreases in left ventricular ejection fraction (LVEF) to below the lower limit of normal (LLN) and cardiac failure, including death, have been observed. Patients with concomitant cardiac conditions should be carefully monitored for clinical signs and symptoms of congestive heart failure. Patients should be monitored for hypertension and treated as needed with standard antihypertensive therapy. Complete blood counts (CBCs) with platelet count and serum chemistries should be performed at the beginning of each treatment cycle for patients receiving treatment with SUTENT.

the most common adverse reactions in GIST, RCC and pancreatic NET clinical trials were diarrhea, fatigue, asthenia, nausea, mucositis/stomatitis, anorexia, vomiting, neutropenia, hypertension, dyspepsia, abdominal pain, constipation, rash, hand-foot syndrome, skin discoloration, hair color changes, altered taste and bleeding.

for more information on SUTENT, including full prescribing information for SUTENT (sunitinib malate), please visit pfizer.com [pfizer.com].

About Pfizer Oncology

Pfizer Oncology is committed to the discovery, investigation and development of innovative treatment options to improve the outlook for cancer patients worldwide. Our strong pipeline, one of the most robust in the industry, is studied with precise focus on identifying and translating the best scientific breakthroughs into clinical application for patients across a wide range of cancers. Pfizer Oncology has biologics and small molecules in clinical development and more than 100 clinical trials underway. By working collaboratively with academic institutions, individual researchers, cooperative research groups, governments, and licensing partners, Pfizer Oncology strives to cure or control cancer with breakthrough medicines, to deliver the right drug for each patient at the right time. for more information please visit Pfizer.com.

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1 Ramage JK, Davies AHG, Ardill et al. Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours. Gut. 2005;54:iv1-16

2 Halfdanarson TR, Rabe KG, Rubin J et al. Pancreatic neuroendocrine tumors (PNETs): incidence, prognosis and recent trend toward improved survival. Ann Oncol. 2008;19:1727-33.

3 SUTENT [Package Insert]. new York, NY: Pfizer, Inc. 2011.

4 Raymond E, et al. Sunitinib Malate for the Treatment of Pancreatic Neuroendocrine Tumors. N Engl J Med 2011; 334: 501-13.

5 ASCO GI Abstract #249. Evaluation of Progression Free Survival by Blinded Independent Central Review in Patients with Progressive, Well-Differentiated Pancreatic Neuroendocrine Tumors Treated with Sunitinib or Placebo. E. Van Cutsem – Presenter. 8th Annual Gastrointestinal (GI) Cancers Symposium, San Francisco, CA, January 20-22, 2011.

6 American Cancer Society. What is cancer of the pancreas? available at: cancer.org/Cancer/PancreaticCancer/DetailedGuide/pancreatic-cancer-what-is-pancreatic-cancer. Accessed March 1, 2011

7 National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology – Neuroendocrine Tumors. Version 1.2011: National Comprehensive Cancer Network, Inc.; 2011.

8 Cancer.net. Neuroendocrine Tumor. available at: cancer.net/patient/Cancer+Types/Neuroendocrine+Tumor. Accessed may 6, 2011.

9 Choi I, Estecio M, et al. Hypomethylation of LINE-1 and Alu in well-differentiated neuroendocrine tumors (pancreatic endocrine tumors and carcinoid tumors). Modern Pathology. 2007; 20:802-810.

10 Pape UF, Berndt U, Muller-Nordhorn J et al. Prognostic factors for long-term outcome in gastroenteropancreatic neuroendocrine tumors. Endocrine-Related Cancers; 15: 1083-97, 2008.

11 Ter-Minassian M, Frauenhoffer CS, Hooshmand SM et al. Prospective analysis of clinical outcomes and prognostic factors in patients with Neuroendocrine tumors (NETs). ASCO Meeting Abstracts; Jun 14; 4044, 2010.

12 Yao JC, Hassan M, Phan A, 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; 26 (18): 3063-72, 2008.

13 Yao JC, et al. Population-based study of islet cell carcinoma. Ann Surg Oncol. 2007;14(12):3492-3500

14 Pal SK, et al “Lack of survival benefit in metastatic breast cancer with newer chemotherapy agents: the City of Hope cancer experience” ASCO Breast 2008; Abstract 95.

15 Kopetz S, Chang G, et al. Improved Survival in Metastatic Colorectal Cancer is associated with Adoption of Hepatic Resection and Improved Chemotherapy. J Clin Oncol. 2009; 7:3677-3683.

Pfizer Inc.Media:Chris Loder, 212-733-7897orInvestors:Jennifer Davis, 212-733-0717

Reporter Duff Wilson had some choice words in his characterization of this beleaguered industry:

they are all struggling with research failures as they scramble to replace their cash cows,… Consumers should see a financial benefit as lower-cost generics replace the expensive elite drugs,… Pfizer paid the largest criminal fine in the nation’s history as part of a $2.3 billion settlement over marketing drugs for unapproved uses. some analysts say larger fraud and foreign bribery cases will come.

As shown in the New York Times (March 7, 2011) graphic, FDA approval of new drugs has been consistently decreasing since 1996, while the pharmaceutical industry continues to invest more and more in research and development, approaching $70 billion last year.

Shouldn’t more money invested in research yield more new medicines? Research, as any scientist knows, is utterly unpredictable – the exact opposite of what any shareholder wants to hear. Many big Pharma corporations compensate for the vagaries of drug discovery by rewarding their longtime shareholders with consistent dividends, often 3 or 4% per year.

To provide some context and a perspective from my years as a scientific researcher in big Pharma, I would like to share my article below that was originally published in the Huffington Post.

Virtually everyone in the U.S. has relied on a prescription drug to alleviate an infection or a chronic disease. how is a drug discovered? how do we know that it is safe and effective? Behind every prescription drug is a story of scientific discovery, innumerable failures and extensive resources that led to eventual approval by the Food and Drug Administration (FDA). the challenges of discovering new medicines sometimes brings to mind the Greek character Sisyphus whose punishment in Hades was to push a boulder up a hill almost to its zenith, only to find that his burden inexorably returns to the bottom. Weary Sisyphus must repeat the task for eternity.

“In the underworld Sisyphus was compelled to roll a big stone up a steep hill; but before it reached the top of the hill the stone always rolled down, and Sisyphus had to begin all over again (Odyssey, xi. 593).”

OK, perhaps this metaphor is overly dramatic, given that many new medicines are discovered regularly. Every now and then, that boulder does reach the tipping point representing a new discovery. Approval of new drugs by the FDA has been declining, with 17 approvals in 2007, the lowest since 1983. going from a “eureka” moment of discovering a candidate for a new drug to final approval by the FDA can take 10 to 15 years, costing on average $1.32 billion per drug. why does it take so long and require such a large investment? because failure rates are high. That drug candidate discovered at the lab bench may have all of the desirable traits, including potency and specificity for the targeted disease, the right physical properties, a good safety profile in animal models such as mice or rats, but fails in the first phase of clinical trails using healthy volunteers. Even those few candidate drugs that pass Phase I of the FDA-required clinical trails, showing safety when given to people, only about one in six succeed to final approval — then the drug can be used as a prescription medicine. the pharmaceutical industry has been fine tuning this process for many decades. how is it done and what is the “best” method? Em and Ernie’s Flickr photostream Consider the proverbial haystack. Buried somewhere in this enormous stack are say five needles, similar but distinct. One of theses needles is golden. There are a number of ways that could help you find that prize needle. First, the methodical. you, along with the help of a team, could remove one blade at a time from the haystack carefully placing it in a separate pile until one of you finds the five needles. the golden needle can then be easily found.

Second, the random hay roll. you could spread out the haystack evenly, then roll around the hay (I know) until one of the needles pokes you. Repeat the process until you find all five needles.

Third, use a detector. you could use a metal detector, scanning the entire haystack. This detector would have to be very sensitive to reveal the location of the tiny needles.

Fourth, use a smart detector. you could use a powerful magnet — so strong that simply holding it near the haystack would pull the needles out of the haystack.

Each of these approaches has been used at one time or another. the current most popular methods are the “random hay roll” and the “smart detector” as ways to measure what could be the next new drug. the “smarter” the detector is, the more potent and effective the medicine will be, reducing chances of adverse side effects.

One of the biggest challenges in finding new medicines is in the battle of infectious diseases, because the disease-causing microbes or organisms are constantly evolving to survive and they mutate quickly. It’s like trying to hit a moving target.

One such moving target is the parasite that causes malaria. Close to half of the world’s population is, at one time or another, exposed to the parasite resulting in more than 800,000 deaths each year. Classical treatments such as chloroquine that were highly effective years ago have become less and less effective as the parasite develops resistance. With each wave of resistance to the medicine, a new medicine must be developed against which the organism inevitably becomes resistant. (See here for an authoritative overview on malaria , which describes symptoms, treatment and prevention.)

A recent paper in the prestigious journal, Science reports the discovery of a new class of potential antimalarial compounds using a traditional approach for their “smart detector.” (For News Focus click here, for a Perspectives, click here.) these scientists found their “golden needle” using a traditional “detector” — the parasite itself. they carefully tested more than 12,000 chemicals, mostly from natural sources, and found 275 possible candidates that were capable of killing the parasite.

How could they find the best one? most approved drugs share common physical properties that can guide these choices. Based on these criteria, only 17 candidates seemed promising. only one from this group showed the most promise as an effective antimalarial treatment, belonging to a chemical class called spiroindolones. But the search doesn’t stop there.

Hoping to fine tune how potent and specific the candidate drug could be, these scientists prepared about 200 related chemicals. from this new group, only one emerged with the desired properties. most importantly, this potential drug is able to kill drug-resistant parasites in mice. so this compound is now poised to be tested in people, as the first Phase of clinical trials.

Could this spiroindolones be the next chloroquine that saved so many lives in the past? Remember that only about one in six candidates succeed, so there are still more mountains to be conquered.