Not intended for US, Canada and UK-based media Merck and Pfizer Inc. (NYSE: PFE) today announced that the US Food and Drug Administration (FDA) has accepted for Priority Review the supplemental Biologics License Application (sBLA) for BAVENCIO(R) (avelumab) in combination with INLYTA(R) (axitinib)* for patients with advanced renal cell carcinoma (RCC). The application has been given a target action date in June 2019. "The combination of BAVENCIO with INLYTA builds on Pfizer's significant heritage in advancing standards of care for patients with advanced RCC and has the potential to make a meaningful impact for the lives of patients," said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global Product Development. "We look forward to working with the FDA to bring this potential new treatment option to patients as quickly as possible." "Our alliance is focused on the development of potential new treatment options for patients with cancers that have high unmet medical needs, including the broad spectrum of people living with advanced RCC," said Luciano Rossetti, M.D., Executive Vice President, Head of Global Research & Development at the Biopharma business of Merck. "This regulatory milestone, which closely follows the acceptance of our application in Japan, represents an important step forward for science and for patients." The submission is based on data from the pivotal Phase III JAVELIN Renal 101 trial, which were presented in a Presidential Symposium at the European Society of Medical Oncology (ESMO) 2018 Congress in Munich. In December 2017, the FDA granted Breakthrough Therapy Designation for BAVENCIO in combination with INLYTA for treatment-naïve patients with advanced RCC. Despite available therapies, the outlook for patients with advanced RCC remains poor. [1] Approximately 20% to 30% of patients are first diagnosed at the metastatic stage.[2] The five-year survival rate for patients with metastatic RCC is approximately 12%.[1] The clinical development program for avelumab, known as JAVELIN, involves at least 30 clinical programs and more than 9,000 patients evaluated across more than 15 different tumor types. In addition to RCC, these tumor types include breast, gastric/gastro-esophageal junction, and head and neck cancers, Merkel cell carcinoma, non-small cell lung cancer, and urothelial carcinoma. *The combination of BAVENCIO and INLYTA is under clinical investigation for advanced RCC, and there is no guarantee this combination will be approved for advanced RCC by any health authority worldwide. In the US, INLYTA is approved as monotherapy for the treatment of advanced RCC after failure of one prior systemic therapy. INLYTA is also approved by the European Medicines Agency (EMA) for use in the EU in adult patients with advanced RCC after failure of prior treatment with SUTENT(R) (sunitinib) or a cytokine. About Renal Cell Carcinoma RCC is the most common form of kidney cancer, accounting for about 2% to 3% of all cancers in adults.[3],[4] The most common type of RCC is clear cell carcinoma, accounting for approximately 70% of all cases.[3] In 2019, an estimated 73,820 new cases of kidney cancer will be diagnosed in the US.[5] About BAVENCIO(R) (avelumab) BAVENCIO is a human anti-programmed death ligand-1 (PD-L1) antibody. BAVENCIO has been shown in preclinical models to engage both the adaptive and innate immune functions. By blocking the interaction of PD-L1 with PD-1 receptors, BAVENCIO has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical models.[6] -[8] BAVENCIO has also been shown to induce NK cell-mediated direct tumor cell lysis via antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro.[8]-[10] In November 2014, Merck and Pfizer announced a strategic alliance to co-develop and co-commercialize BAVENCIO. Approved Indications in the US In the US, the FDA granted accelerated approval for BAVENCIO for the treatment of (i) adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (mMCC) and (ii) patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy, or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. These indications are approved under accelerated approval based on tumor response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials. BAVENCIO is currently approved for patients with MCC in more than 45 countries globally, with the majority of these approvals in a broad indication that is not limited to a specific line of treatment. Important Safety Information from the US FDA Approved Label The warnings and precautions for BAVENCIO include immune-mediated adverse reactions (such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis and renal dysfunction, and other adverse reactions), infusion-related reactions and embryo-fetal toxicity. Common adverse reactions (reported in at least 20% of patients) in patients treated with avelumab for mMCC and patients with locally advanced or mUC include fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, peripheral edema, decreased appetite/hypophagia, urinary tract infection and rash. About INLYTA(R) (axitinib) INLYTA is an oral therapy that is designed to inhibit tyrosine kinases, including vascular endothelial growth factor (VEGF) receptors 1, 2 and 3; these receptors can influence tumor growth, vascular angiogenesis and progression of cancer (the spread of tumors). In the US, INLYTA is approved for the treatment of advanced renal cell carcinoma (RCC) after failure of one prior systemic therapy. INLYTA is also approved by the European Medicines Agency (EMA) for use in the EU in adult patients with advanced RCC after failure of prior treatment with sunitinib or a cytokine. INLYTA Important Safety Information from the US FDA Approved Label In the study of advanced RCC after failure of one prior systemic therapy, the warnings and precautions for INLYTA include hypertension, including hypertensive crisis, arterial and venous thrombotic events, hemorrhagic events, cardiac failure, gastrointestinal perforation and fistula, hypothyroidism, wound healing complications, reversible posterior leukoencephalopathy syndrome (RPLS), proteinuria, liver enzyme elevation, hepatic impairment, and fetal harm during pregnancy. Common adverse events (reported in at least 20% of patients) in patients receiving INLYTA were diarrhea, hypertension, fatigue, decreased appetite, nausea, dysphonia, hand-foot syndrome, weight decreased, vomiting, asthenia, and constipation. For more information and full Prescribing Information, visit www.INLYTA.com [http://www.INLYTA.com ]. About SUTENT(R) (sunitinib malate) Sunitinib is a small molecule that inhibits multiple receptor tyrosine kinases, some of which are implicated in tumor growth, pathologic angiogenesis, and metastatic progression of cancer. Sunitinib was evaluated for its inhibitory activity against a variety of kinases (>80 kinases) and was identified as an inhibitor of platelet-derived growth factor receptors (PDGFRalpha and PDGFRbeta), vascular endothelial growth factor receptors (VEGFR1, VEGFR2 and VEGFR3), stem cell factor receptor (KIT), Fms-like tyrosine kinase-3 (FLT3), colony stimulating factor receptor Type 1 (CSF-1R), and the glial cell-line derived neurotrophic factor receptor (RET). SUTENT is indicated in the US for the treatment of gastrointestinal stromal tumor (GIST) after disease progression on or intolerance to imatinib mesylate; the treatment of advanced RCC; the adjuvant treatment of adult patients at high risk of recurrent RCC following nephrectomy; and the treatment of progressive, well-differentiated pancreatic neuroendocrine tumors (pNET) in patients with unresectable locally advanced or metastatic disease. SUTENT Important Safety Information from the US FDA Approved Label Boxed Warning/Hepatotoxicity has been observed in clinical trials and postmarketing experience. Hepatotoxicity may be severe, and in some cases fatal. Monitor hepatic function and interrupt, reduce, or discontinue dosing as recommended. Fatal liver failure has been observed. Monitor liver function tests before initiation of treatment, during each cycle of treatment, and as clinically indicated. Interrupt SUTENT for Grade 3 or 4 drug-related hepatic adverse reactions and discontinue if there is no resolution. Do not restart SUTENT if patients subsequently experience severe changes in liver function tests or have signs and symptoms of liver failure. Additional warnings and precautions for SUTENT include cardiovascular events, QT prolongation and Torsades de Pointes, hypertension, hemorrhagic events, tumor lysis syndrome (TLS), thrombotic microangiopathy (TMA), proteinuria, dermatologic toxicities including erythema multiforme, Sevens-Johnson syndrome, and toxic epidermal necrolysis, necrotizing fasciitis, thyroid dysfunction, hypoglycemia, osteonecrosis of the jaw (ONJ), impaired wound healing, embryo fetal toxicity and impaired reproductive potential, potential harm during lactation, venous thromboembolic events, reversible posterior leukoencephalopathy syndrome (RPLS), and pancreatic function. Common adverse reactions (reported in at least 20% of patients) in patients receiving SUTENT for treatment-naïve metastatic RCC were diarrhea, fatigue, nausea, anorexia, altered taste, mucositis/stomatitis, pain in extremity/limb discomfort, vomiting, bleeding, all sites, hypertension, dyspepsia, arthralgia, abdominal pain, rash, hand-foot syndrome, back pain, cough, asthenia, dyspnea, skin discoloration/yellow skin, peripheral edema, headache, constipation, dry skin, fever, and hair color changes. Common adverse reactions (reported in at least 20% of patients) in patients receiving SUTENT for adjuvant treatment of RCC, GIST or pNET - and more commonly than in patients given placebo - were mucositis/stomatitis/oral syndromes, diarrhea, fatigue, asthenia, hand-foot syndrome, hypertension, altered taste, nausea, dyspepsia, abdominal pain, hypothyroidism/TSH increased, rash, hair color changes, anorexia, skin discoloration, constipation, vomiting, bleeding events, epistaxis, and dysgeusia. For more information and full Prescribing Information, visit www.SUTENT.com [http://www.SUTENT.com ]. About Merck-Pfizer Alliance Immuno-oncology is a top priority for Merck and Pfizer. The global strategic alliance between Merck and Pfizer enables the companies to benefit from each other's strengths and capabilities and further explore the therapeutic potential of avelumab, an anti-PD-L1 antibody initially discovered and developed by Merck. The immuno-oncology alliance is jointly developing and commercializing avelumab and advancing Pfizer's PD-1 antibody. The alliance is focused on developing high-priority international clinical programs to investigate avelumab as a monotherapy as well as combination regimens, and is striving to find new ways to treat cancer. All Merck Press Releases are distributed by e-mail at the same time they become available on the Merck Website. Please go to www.merckgroup.com/subscribe [http://www.merckgroup.com/subscribe ] to register online, change your selection or discontinue this service. About Merck Merck, a leading science and technology company, operates across healthcare, life science and performance materials. Around 51,000 employees work to make a positive difference to millions of people's lives every day by creating more joyful and sustainable ways to live. From advancing gene editing technologies and discovering unique ways to treat the most challenging diseases to enabling the intelligence of devices - the company is everywhere. In 2017, Merck generated sales of EUR 15.3 billion in 66 countries. Scientific exploration and responsible entrepreneurship have been key to Merck's technological and scientific advances. This is how Merck has thrived since its founding in 1668. The founding family remains the majority owner of the publicly listed company. Merck holds the global rights to the Merck name and brand. The only exceptions are the United States and Canada, where the business sectors of Merck operate as EMD Serono in healthcare, MilliporeSigma in life science, and EMD Performance Materials. Pfizer Inc.: Working together for a healthier world(R) At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products. Our global portfolio includes medicines and vaccines as well as many of the world's best-known consumer health care 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 one of the world's premier innovative biopharmaceutical companies, we 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, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.pfizer.com In addition, to learn more, please visit us on www.pfizer.com and follow us on Twitter at @Pfizer and @Pfizer_News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer. Pfizer Disclosure Notice The information contained in this release is as of February 11, 2019. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments. This release contains forward-looking information about BAVENCIO (avelumab), including a potential new indication for BAVENCIO in combination with INLYTA (axitinib) for the treatment of patients with advanced renal cell carcinoma, the alliance between Merck and Pfizer involving BAVENCIO and clinical development plans, including their potential benefits, that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include, among other things, uncertainties regarding the commercial success of BAVENCIO; the uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for our clinical trials, regulatory submission dates, regulatory approval dates and/or launch dates, as well as the possibility of unfavorable further analyses of existing clinical data and uncertainties regarding whether the other primary endpoint of JAVELIN Renal 101 will be met; risks associated with interim data; the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities; whether regulatory authorities will be satisfied with the design of and results from our clinical studies; whether and when any drug applications may be filed for BAVENCIO in combination with INLYTA for the potential new indication in any other jurisdictions or in any jurisdictions for any other potential indications for BAVENCIO or combination therapies; whether and when the pending applications in the U.S. and Japan for BAVENCIO in combination with INLYTA for the potential new indication may be approved and whether and when regulatory authorities in any jurisdictions where any other applications are pending or may be submitted for BAVENCIO or combination therapies may approve any such applications, which will depend on myriad factors, including making a determination as to whether the product's benefits outweigh its known risks and determination of the product's efficacy, and, if approved, whether they will be commercially successful; decisions by regulatory authorities impacting labeling, manufacturing processes and/or other matters that could affect the availability or commercial potential of BAVENCIO or combination therapies, including BAVENCIO in combination with INLYTA for the potential new indication; and competitive developments. A further description of risks and uncertainties can be found in Pfizer's Annual Report on Form 10-K for the fiscal year ended December 31, 2017, and in its subsequent reports on Form 10-Q, including in the sections thereof captioned "Risk Factors" and "Forward-Looking Information and Factors That May Affect Future Results", as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S. Securities and Exchange Commission and available at www.sec.gov and www.pfizer.com References 1) National Cancer Institute: SEER Stat Fact Sheets: Kidney and renal pelvis. Available from: http://seer.cancer.gov/statfacts/html/kidrp.html. Accessed February 2019. 2) Ljungberg B, Campbell S and Cho H. The Epidemiology of Renal Cell Carcinoma. Eur Urol. 2011;60:615-621. 3) American Cancer Society. What is kidney cancer? Available from: https://www.cancer.org/cancer/kidney-cancer/about.html. Accessed February 2019. 4) Escudier B, Porta C, Schmidinger M et al Renal cell carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Annal Oncol. 2014; 25(Suppl3):iii49-iii56. 5) American Cancer Society. Cancer facts and figures 2019. Available at: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2019/cancer-facts-and-figures-2019.pdf. Accessed February 2019 6) Dolan DE, Gupta S. PD-1 pathway inhibitors: changing the landscape of cancer immunotherapy. Cancer Control. 2014;21(3):231-237. 7) Dahan R, Sega E, Engelhardt J, Selby M, Korman AJ, Ravetch JV. FcgammaRs modulate the anti-tumor activity of antibodies targeting the PD-1/PD-L1 axis. Cancer Cell. 2015;28 (3):285-295. 8) Boyerinas B, Jochems C, Fantini M, et al. Antibody-dependent cellular cytotoxicity activity of a novel anti-PD-L1 antibody avelumab (MSB0010718C) on human tumor cells. Cancer Immunol Res. 2015;3(10):1148-1157. 9) Kohrt HE, Houot R, Marabelle A, et al. Combination strategies to enhance antitumor ADCC. Immunotherapy. 2012;4(5):511-527. 10) Hamilton G, Rath B. Avelumab: combining immune checkpoint inhibition and antibody-dependent cytotoxicity. Expert Opin Biol Ther. 2017;17(4):515-523. Merck: Media Relations: +49-151-1454-6328 friederike.segeberg@merckgroup.com Investor Relations: +49-6151-72-3321 investor.relations@merckgroup.com Pfizer: Media Relations: +1-212-733-6213 jessica.m.smith@pfizer.com Investor Relations: +1-212-733-8160 ryan.crowe@pfizer.com (Logo: https://mma.prnewswire.com/media/611425/Merck_Pfizer_Logo.jpg ) Source: Merck