Pfizer Announces EMA Acceptance of Regulatory Submissions

PfizerPfizer Inc. announced that the European Medicines Agency (EMA) has accepted Pfizer's regulatory submissions for review of two investigational compounds - crizotinib, an oral first-in-class anaplastic lymphoma kinase (ALK) inhibitor, for the treatment of patients with previously treated ALK-positive advanced non-small cell lung cancer (NSCLC); and bosutinib for the treatment of adult patients with newly diagnosed Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in the chronic phase.

"With the EMA submissions for crizotinib and bosutinib, we are one step closer to potentially bringing two promising agents to patient populations in areas of significant unmet medical need," said Dr. Andreas Penk, president of Pfizer Oncology Europe. "These filings underscore Pfizer's commitment to delivering innovative therapeutic treatment options targeting various tumor types and improving the outcome for cancer patients worldwide."

About Crizotinib
In clinical trials of crizotinib, patients were prospectively screened for the ALK gene alteration, indicating their likelihood to respond to the treatment. By inhibiting ALK, crizotinib blocks signaling in a number of cell pathways that are believed to be critical for the growth and survival of tumor cells.(1) Preliminary epidemiology suggests that approximately 3-5 percent of NSCLC tumors are ALK-positive.(2,3,4,5,6,7,8,9)

Crizotinib is being further evaluated in two randomized Phase 3 trials in patients with ALK-positive NSCLC: PROFILE 1014 and PROFILE 1007 will compare the safety and efficacy of crizotinib to standard-of-care chemotherapy as a first-line and second-line therapy, respectively.(10,11)

Worldwide, lung cancer is the leading cause of cancer death in both men and women.12 In Europe, lung cancer accounts for 20 percent of all cancer-related deaths.(13) NSCLC accounts for about 85 percent of lung cancer cases and remains difficult to treat, particularly in the metastatic setting. Approximately 75 percent of NSCLC patients are diagnosed late with metastatic, or advanced, disease, where the five-year survival rate is only 6 percent. (14,15) In addition, the current standard of care for patients with advanced NSCLC demonstrates a response rate of about 9-35 percent.(16,17)

About Bosutinib
Bosutinib is an investigational oral dual Src and Abl kinase inhibitor with minimal inhibitory activity against c-kit and PDGFR.(18) It is believed that by dual inhibition of the Src and Abl tyrosine kinases, bosutinib may inhibit signaling in CML cells that allows the cells to grow, survive and reproduce.(19)

Chronic myeloid leukemia (CML), one of the four main types of leukemia,(20) accounts for 15 percent of all leukemias worldwide.(21) A hallmark of CML is an abnormal chromosome known as the Philadelphia Chromosome, a DNA mutation that initiates a series of events leading to the development of Bcr-Abl, a tyrosine kinase that causes CML cells to grow and reproduce rapidly.(22)

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.

Pfizer Inc.: Working together for a healthier world™
At Pfizer, we apply science and our global resources to improve health and well-being at every stage of life. We strive to set the standard for quality, safety and value in the discovery, development and manufacturing of medicines for people and animals. Our diversified global health care portfolio includes human and animal biologic and small molecule medicines and vaccines, as well as nutritional products and many of the world's best-known consumer products. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as the world's leading biopharmaceutical company, we also collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 150 years, Pfizer has worked to make a difference for all who rely on us.

1. Horn L, Pao W. EML4-ALK: honing in on a new target in non-small-cell lung cancer. J Clin Oncol. 2009;27(26):4232-4235.
2. Soda M, Choi YL, Enomoto M, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 2007;448:561-566
3. Garber K. ALK, lung cancer, and personalized therapy: portent of the future? J Natl Cancer Inst. 2010;102:672-675.
4. Takeuchi K, Choi YL, Soda M, et al. Multiplex Reverse Transcription-PCR Screening for EML4-ALK Fusion Transcripts. Clin Cancer Res: 2008;14: 6618-24.
5. Palmer RH, Vernersson E, Grabbe C, et al. Anaplastic lymphoma kinase: signaling in development and disease. Biochem J. 2009;420:345-361.
6. Mosse YP, Wood A, Maris JM. Inhibition of ALK signaling for cancer therapy. Clin Cancer Res. 2009;15:5609-14.
7. Sasaki T, Rodig SJ, Chirieac LR, et al. The biology and treatment of EML4-ALK non-small cell lung cancer. Eur J Cancer. 2010;46:1773-80.
8. Koivunen JP, Mermel C, Zejnullahu K, et al. EML4-ALK fusion gene and efficacy of an ALK kinase inhibitor in lung cancer. Clin Cancer Res. 2008; 14:4275-83.
9. Wong DW, Leung EL, So KK, et al. The EML4-ALK Fusion Gene Is involved in Various Histologic Types of Lung Cancers From Nonsmokers with Wild-type EGFR and KRAS. Cancer. 2009;115:1723–33.
10. ClinicalTrials.gov. A Clinical Trial Testing The Efficacy Of Crizotinib Versus Standard Chemotherapy Pemetrexed Plus Cisplatin Or Carboplatin In Patients With ALK Positive Non Squamous Cancer Of The Lung (PROFILE 1014). Available at: http://clinicaltrials.gov/ct2/show/NCT01154140?term=1014&rank=1. Accessed February 22, 2011.
11. ClinicalTrials.gov. An Investigational Drug, PF-02341066 Is Being Studied Versus Standard Of Care in Patients With Advanced Non-Small Cell Lung Cancer With A Specific Gene Profile Involving The Anaplastic Lymphoma Kinase (ALK) Gene. Available at: http://clinicaltrials.gov/ct2/show/NCT00932893. Accessed February 22, 2011
12. World Health Organization. Cancer. Available at: http://www.who.int/mediacentre/factsheets/fs297/en/. Accessed August 17, 2011.
13. European Lung Foundation. What is Lung Cancer? Available at: http://www.european-lung-foundation.org/index.php?id=65. Accessed July 15, 2011.
14. Reade CA, Ganti AK. EGFR targeted therapy in non-small cell lung cancer: potential role of cetuximab. Biologics. 2009; 3: 215–224.
15. American Cancer Society. Detailed guide: lung cancer – non-small cell. Non-small cell lung cancer survival rates by stage. http://www.cancer.org/Cancer/LungCancer-Non-SmallCell/DetailedGuide/index. Accessed February 8, 2011.
16. Sandler A, Gray R, Perry MC, et al. Paclitaxel–carboplatin alone or with bevacizumab for non–small-cell lung cancer. New England Journal of Medicine. 2006;355:2542-50. [Erratum, N Engl J Med 2007;356:318.]
17. Hanna, et al., Journ Clin Oncol 2004; 22: p1589.
18. Gambacorti-Passerini C et al. Bosutinib (SKI-606) Demonstrates Clinical Activity and is Well Tolerated in Patients with AP and BP CML and Ph+ ALL. Poster Presented at the American Society of Hematology Meeting, December 6-9, 2008, San Francisco, CA. Wyeth.
19. Konig H et al. Effects of Dasatinib on Src Kinase Activity and Downstream Intracellular Signaling in Primitive Chronic Myelogenous Leukemia Hematopoietic Cells. Cancer Research. 2008; 68: 9624-9633.
20. National Cancer Institute. What you need to know about leukemia – Types of Leukemia. Available here: http://www.cancer.gov/cancertopics/wyntk/leukemia/page3. Accessed November 16, 2010.
21. Jabbour E et al. Targeted Therapy in Chronic Myeloid Leukemia. Expert Review of Anticancer Therapy. 2008; 8: 99-110.
22. American Cancer Society. Detailed Guide: Leukemia – Chronic Myeloid (Myelogenous). Available at: http://www.cancer.org/acs/groups/cid/documents/webcontent/003112-pdf.pdf. Accessed November 16, 2010.

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