• Second Breakthrough Therapy Designation for avelumab in hard-to-treat cancer
• Renal cell carcinoma, the most common form of kidney cancer, has a poor prognosis in advanced stage1,2
• Javelin Renal clinical development program is ongoing, including Phase III first-line study

December 21, 2017 I Merck KGaA, Darmstadt, Germany, which operates its biopharmaceutical business as EMD Serono in the US and Canada, and Pfizer Inc. (NYSE: PFE) today announced that the US Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation for avelumab in combination with INLYTA® (axitinib)* for treatment-naïve patients with advanced renal cell carcinoma (RCC). Breakthrough Therapy Designation is designed to accelerate the development and review of potential medicines for serious conditions, and preliminary clinical evidence indicates that the therapy may demonstrate a substantial improvement over currently available therapies on one or more clinically significant endpoints. This is the second Breakthrough Therapy Designation granted to avelumab.

“A combination approach with an immunotherapy, whose activity may complement existing agents such as INLYTA, has the potential to improve outcomes for patients with advanced renal cancer – a disease where the five-year survival rate remains low,” said Chris Boshoff, M.D., Ph.D., Senior Vice President and Head of Immuno-Oncology, Early Development and Translational Oncology, Pfizer Global Product Development. “Pfizer’s expertise in developing treatments for advanced RCC is a distinct advantage in tackling this tumor type, and we look forward to the completion of our Phase III study combining avelumab with INLYTA, which we’re expecting at the end of next year.”

“This announcement reinforces the need for innovative first-line treatments for advanced RCC and our promise to advancing care for these patients,” said Luciano Rossetti, M.D., Global Head of Research & Development at the Biopharma business of Merck KGaA, Darmstadt, Germany. “The second Breakthrough Therapy Designation by the FDA in another hard-to-treat cancer underlines our focus on challenging tumor types.”

RCC is the most common form of kidney cancer, with an estimated 57,500 new cases diagnosed in the US in 2017.1,3 This disease is serious and life-threatening, and approximately 20–30% of patients are first diagnosed at an advanced or metastatic stage.4

The Breakthrough Therapy Designation is based on the preliminary evaluation of clinical data from JAVELIN Renal 100, a global Phase Ib study assessing the safety and efficacy of avelumab in combination with INLYTA for the treatment of treatment-naïve patients with advanced RCC. Updated results from this Phase Ib study were presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting. The FDA previously granted avelumab Breakthrough Therapy Designation for the treatment of patients with metastatic Merkel cell carcinoma (mMCC) whose disease has progressed after at least one previous chemotherapy regimen.

The clinical development program for avelumab, known as JAVELIN, involves at least 30 clinical programs and over 7,000 patients evaluated across more than 15 different tumor types. This includes JAVELIN Renal 101, a randomized, Phase III, open-label, multicenter trial investigating avelumab in combination with INLYTA versus sunitinib as a first-line treatment option for advanced RCC, which recently completed recruitment. In addition to RCC, cancer studies in the JAVELIN program include non-small cell lung cancer, breast cancer, head and neck cancer, Hodgkin’s lymphoma, melanoma, mesothelioma, MCC, ovarian cancer, gastric/gastroesophageal junction cancer, and urothelial carcinoma (UC).

*Avelumab is under clinical investigation for advanced renal cell carcinoma and has not been demonstrated to be safe and effective for this indication. There is no guarantee that avelumab will be approved for advanced renal cell carcinoma by any health authority worldwide. INLYTA is under clinical investigation for this use in combination with avelumab. In the US, INLYTA is approved as monotherapy for the treatment of advanced RCC after failure of one prior systemic therapy.

About the FDA Designation
Breakthrough Therapy Designation is designed to expedite the development and review of drugs which are intended to treat a serious condition, and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s). The FDA’s granting of the Breakthrough Therapy Designation for metastatic RCC does not alter the standard regulatory requirement to establish the safety and effectiveness of a drug through adequate and well-controlled studies to support approval.

About Renal Cell Carcinoma (RCC)
RCC is the most common form of kidney cancer, accounting for about 2–3% of all cancers in adults.1,5 The most common type of RCC is clear cell carcinoma, accounting for approximately 70% of all cases.3 In 2012, there were approximately 304,000 new cases of RCC diagnosed worldwide, with an estimated 57,500 cases in the US alone in 2017.3,4,6 Incidence varies substantially worldwide with generally higher rates seen in Eastern Asia, North America and Central/Eastern Europe.7 The five-year overall survival rate for patients with distant metastatic RCC is approximately 12%.2

About JAVELIN Renal 100
JAVELIN Renal 100 is a Phase Ib, open-label, multicenter, multiple-dose study investigating avelumab in combination with INLYTA® (axitinib), a tyrosine kinase inhibitor from Pfizer, for the treatment of treatment-naïve patients with advanced RCC. The study enrolled 55 patients from participating sites in the US, United Kingdom and Japan.

About Avelumab
Avelumab is a human anti-programmed death ligand-1 (PD-L1) antibody. Avelumab 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, avelumab has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical models.7-9 Avelumab has also been shown to induce NK cell-mediated direct tumor cell lysis via antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro.9-11 In November 2014, Merck KGaA, Darmstadt, Germany, and Pfizer announced a strategic alliance to co-develop and co-commercialize avelumab.

Approved Indications in the US
The FDA granted accelerated approval for avelumab (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 (UC) 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.

About INLYTA® (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 U.S., INLYTA is approved 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 sunitinib or a cytokine.

About Merck KGaA, Darmstadt, Germany
Merck KGaA, Darmstadt, Germany, is a leading science and technology company in healthcare, life science and performance materials. Around 50,000 employees work to further develop technologies that improve and enhance life – from biopharmaceutical therapies to treat cancer or multiple sclerosis, cutting-edge systems for scientific research and production, to liquid crystals for smartphones and LCD televisions. In 2016, Merck KGaA, Darmstadt, Germany, generated sales of € 15.0 billion in 66 countries.

Founded in 1668, Merck KGaA, Darmstadt, Germany, is the world’s oldest pharmaceutical and chemical company. The founding family remains the majority owner of the publicly listed corporate group. Merck KGaA, Darmstadt, Germany, holds the global rights to the “Merck” name and brand except in the United States and Canada, where the company operates as EMD Serono, MilliporeSigma and EMD Performance Materials.

About EMD Serono, Inc.
EMD Serono is the biopharmaceutical business of Merck KGaA, Darmstadt, Germany – a leading science and technology company – in the US and Canada focused exclusively on specialty care. For more than 40 years, the business has integrated cutting-edge science, innovative products and industry-leading patient support and access programs. EMD Serono has deep expertise in neurology, fertility and endocrinology, as well as a robust pipeline of potential therapies in oncology, immuno-oncology and immunology as R&D focus areas. Today, the business has 1,200 employees around the country with commercial, clinical and research operations based in the company’s home state of Massachusetts.

About Pfizer: Working together for a healthier world®
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.

1. American Cancer Society. What is kidney cancer? Available from: http://www.cancer.org/cancer/kidneycancer/detailedguide/kidney-cancer-ad…. Accessed November 2017.
2. National Cancer Institute: SEER Stat Fact Sheets: Kidney and Renal Pelvis. Available from: http://seer.cancer.gov/statfacts/html/kidrp.html. Accessed November 2017.
3. American Cancer Society. What are the key statistics about kidney cancer? Available from: https://www.cancer.org/cancer/kidney-cancer/about/key-statistics.html. Accessed November 2017.
4. Ljungberg B, Campbell S, Cho H. The Epidemiology of Renal Cell Carcinoma. Eur Urol. 2011;60:615-621.
5. Escudier B, et al. Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016;24(5):v58-v68.
6. World Cancer Research Fund International: Kidney Cancer statistics. Available from: http://www.wcrf.org/int/cancer-facts-figures/data-specific-cancers/kidne…. Accessed November 2017.
7. International Agency for Research on Cancer (IARC)/World Health Organization. GLOBOCAN 2012: Kidney, adults. Available from: http://globocan.iarc.fr/old/bar_-sex_site_prev.asp?selection=10210&title…. Accessed March 2016.
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9. Dahan R, Sega E, Engelhardt J, et al. FcγRs modulate the anti-tumor activity of antibodies targeting the PD-1/PD-L1 axis.Cancer Cell. 2015;28(3):285-295.
10. 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.
11. Kohrt HE, Houot R, Marabelle A, et al. Combination strategies to enhance antitumor ADCC. Immunotherapy. 2012;4(5):511-527.
12. Hamilton G, Rath B. Avelumab: combining immune checkpoint inhibition and antibody-dependent cytotoxicity. Expert Opin Biol Ther. 2017;17(4):515-523.

SOURCE: Pfizer