European Commission Approves BAVENCIO® (avelumab) Plus Axitinib Combination for First-Line Treatment of Patients With Advanced Renal Cell Carcinoma

-- EU approval based on JAVELIN Renal 101 trial results demonstrating significant improvement in progression-free survival with BAVENCIO in combination with axitinib compared with sunitinib

-- Combination regimen approved across all IMDC prognostic risk groups and irrespective of PD-L1 expression

ROCKLAND, MA and NEW YORK, NY, USA I October 28, 2019 I EMD Serono, the biopharmaceutical business of Merck KGaA, Darmstadt, Germany in the US and Canada, and Pfizer Inc. (NYSE: PFE) today announced that the European Commission (EC) has approved BAVENCIO® (avelumab) in combination with axitinib for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC). The approval was based on positive interim results from the Phase III JAVELIN Renal 101 study, which demonstrated that BAVENCIO in combination with axitinib significantly lowered risk of disease progression or death by 31% (HR: 0.69 [95% CI: 0.574–0.825; p<0.0001]) and nearly doubled objective response rate (ORR; 52.5% [95% CI: 47.7-57.2] vs. 27.3% [95% CI: 23.2-31.6]) compared with sunitinib in patients with advanced RCC regardless of PD-L1 status. The study included patients across International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic risk groups. Improvement in progression-free survival (PFS) was observed across pre-specified subgroups in patients receiving the treatment combination.1 EMD Serono and Pfizer have a global strategic alliance to jointly develop and commercialize BAVENCIO.

"There is a high incidence of kidney cancer in Europe, and for the most common type, renal cell carcinoma, we continue to need additional treatment options, particularly for patients with advanced disease, where outcomes are poorest," said Professor James Larkin, Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust and Professor at the Institute of Cancer Research (ICR). "We've seen a demonstrated efficacy benefit and safety and tolerability profile for avelumab in combination with axitinib across all prognostic risk groups in patients with advanced renal cell carcinoma, so today's approval in Europe brings an important option that can help healthcare professionals optimize treatment strategies across risk stratification."

In 2018, an estimated 136,500 new cases of kidney cancer were diagnosed in Europe, and approximately 54,700 people died from the disease.2 Many patients living with advanced RCC do not go on to receive additional treatment after first-line therapy,3,4 for reasons that may include poor performance status or adverse events from their initial treatment.3,5,6 The five-year survival rate for patients with advanced RCC is approximately 12%.7

"This first European approval of an anti-PD-L1 as part of a combination treatment for advanced renal cell carcinoma builds on our commitment to bringing innovative treatment options to patients with hard-to-treat cancers through our extensive JAVELIN clinical trial program," said Rehan Verjee, Global Head of Innovative Medicine Franchises for the Biopharma business of Merck KGaA, Darmstadt, Germany, and President, EMD Serono. "RCC is the most common form of kidney cancer, accounting for 90% of diagnoses. We are now working to make BAVENCIO in combination with axitinib available for patients with advanced renal cell carcinoma as quickly as possible."

"The European Commission approval of BAVENCIO in combination with axitinib has the potential to bring even more patients with advanced renal cell carcinoma a new first-line treatment, and it allows us to continue to deliver on our more than decade-long passion to do more for patients with kidney cancer," said Andy Schmeltz, Global President, Pfizer Oncology. "We thank all of the researchers, doctors, advocates, patients and their families who helped get us here today, and we will continue in our fight against this advanced cancer."

The EC's decision follows the U.S. Food and Drug Administration (FDA) approval of BAVENCIO in combination with axitinib for the first-line treatment of patients with advanced RCC in May 2019. A supplemental application for BAVENCIO in combination with axitinib in unresectable or metastatic RCC was submitted in Japan in January 2019.

Additionally, with this approval, the posology section of the Summary of Product Characteristics for BAVENCIO has been updated. The recommended dose of BAVENCIO as monotherapy is 800 mg administered intravenously over 60 minutes every 2 weeks. Administration of BAVENCIO should continue according to the recommended schedule until disease progression or unacceptable toxicity. The recommended dose of BAVENCIO in combination with axitinib is 800 mg administered intravenously over 60 minutes every 2 weeks and axitinib 5 mg orally taken twice daily (12 hours apart) with or without food until disease progression or unacceptable toxicity.1

Data from JAVELIN Renal 101 Study Supporting Approval
This approval was based on interim data from the Phase III JAVELIN Renal 101 study, a randomized, multicenter, open-label study of BAVENCIO in combination with axitinib in 886 patients with untreated advanced or metastatic RCC with a clear cell component. The study included patients across risk groups (International Metastatic Renal Cell Carcinoma Database Consortium [IMDC]: 21% favorable, 62% intermediate and 16% poor; Memorial Sloan Kettering Cancer Center [MSKCC]: 22% favorable, 65% intermediate and 11% poor). The primary efficacy endpoints were progression-free survival (PFS) as assessed by a Blinded Independent Central Review (BICR) using RECIST v1.1 and overall survival (OS) in the first-line treatment of patients with advanced RCC who have PD-L1-positive tumors (PD‑L1 expression level ≥1%). PFS based on BICR assessment per RECIST v1.1 and OS irrespective of PD‑L1 expression, objective response (OR), time to response (TTR), duration of response (DOR) and safety are included as secondary endpoints. The study is continuing for OS.

In the analysis, BAVENCIO in combination with axitinib significantly improved median PFS compared with sunitinib by more than five months in patients irrespective of PD-L1 expression (13.3 months [95% CI: 11.1–15.3] vs. 8.0 months [95% CI: 6.7–9.8]). With a median follow-up for OS of 19 months, data for the trial's other primary endpoint of OS were immature, with 27% of deaths, and the trial is continuing as planned. The hazard ratio for OS in patients treated with BAVENCIO in combination with axitinib compared with sunitinib was 0.80 (95% CI: 0.616, 1.027) at the interim analysis.

The most common adverse reactions were diarrhea (62.8%), hypertension (49.3%), fatigue (42.9%), nausea (33.5%), dysphonia (32.7%), decreased appetite (26.0%), hypothyroidism (25.2%), cough (23.7%), headache (21.3%), dyspnea (20.9%), and arthralgia (20.9%).

About the JAVELIN Clinical Development Program
The clinical development program for avelumab, known as JAVELIN, involves at least 30 clinical programs and more than 10,000 patients evaluated across more than 15 different tumor types. In addition to RCC, these tumor types include gastric/gastro-esophageal junction cancer, head and neck cancer, Merkel cell carcinoma, non-small cell lung cancer and urothelial carcinoma.

About BAVENCIO® (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.8-10 In November 2014, EMD Serono and Pfizer announced a strategic alliance to co-develop and co-commercialize BAVENCIO.

BAVENCIO Approved Indications in the US
BAVENCIO® (avelumab) in combination with axitinib is indicated in the US for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

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. 

Avelumab is currently approved for patients with MCC in 50 countries globally, with the majority of these approvals in a broad indication that is not limited to a specific line of treatment.

About Merck KGaA, Darmstadt, Germany-Pfizer Alliance
Immuno-oncology is a top priority for Merck KGaA, Darmstadt, Germany and Pfizer. The global strategic alliance between Merck KGaA, Darmstadt, Germany and Pfizer enables the companies to benefit from each other's strengths and capabilities and further explore the therapeutic potential of BAVENCIO, an anti-PD-L1 antibody initially discovered and developed by Merck KGaA, Darmstadt, Germany. The immuno-oncology alliance is jointly developing and commercializing BAVENCIO. The alliance is focused on developing high-priority international clinical programs to investigate BAVENCIO as a monotherapy as well as combination regimens, and is striving to find new ways to treat cancer.

All Merck KGaA, Darmstadt, Germany, press releases are distributed by e-mail at the same time they become available on the EMD Group Website. In case you are a resident of the USA or Canada please go to www.emdgroup.com/subscribe to register again for your online subscription of this service as our newly introduced geo-targeting requires new links in the email. You may later change your selection or discontinue this service.

About EMD Serono, Inc.
EMD Serono - the biopharmaceutical business of Merck KGaA, Darmstadt, Germany, in the U.S. and Canada - is engaged in the discovery, research and development of medicines for patients with difficult to treat diseases. The business is committed to transforming lives by developing and delivering meaningful solutions that help address the therapeutic and support needs of individual patients. Building on a proven legacy and deep expertise in neurology, fertility and endocrinology, EMD Serono is developing potential new oncology and immuno-oncology medicines while continuing to explore potential therapeutic options for diseases such as psoriasis, lupus and MS. Today, the business has approximately 1,500 employees around the country with commercial, clinical and research operations based in the company's home state of Massachusetts. www.emdserono.com.

About Merck KGaA, Darmstadt, Germany
Merck KGaA, Darmstadt, Germany, a leading science and technology company, operates across healthcare, life science and performance materials. Around 56,000 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 2018, Merck KGaA, Darmstadt, Germany, generated sales of € 14.8 billion in 66 countries.

The company holds the global rights to the name and trademark "Merck" internationally. The only exceptions are the United States and Canada, where the business sectors of Merck KGaA, Darmstadt, Germany operate as EMD Serono in healthcare, MilliporeSigma in life science, and EMD Performance Materials. Since its founding 1668, scientific exploration and responsible entrepreneurship have been key to the company's technological and scientific advances. To this day, the founding family remains the majority owner of the publicly listed company.

Pfizer Inc.: Breakthroughs that change patients' lives
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, including innovative medicines and vaccines. 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.

References

  1. BAVENCIO® (avelumab) EU SmPC. Available from: http://www.ema.europa.eu/ema/. Accessed October 2019.
  2. Ferlay J, Colombet M, Soerjomataram I, et al. Cancer incidence and mortality patterns in Europe: Estimates for 40 countries and 25 major cancers in 2018. Eur J Cancer. 2018;103:356-387.
  3. Eggers H, Ivanyi P, Hornig M, Grünwald V. Predictive factors for second-line therapy in metastatic renal cell carcinoma: a retrospective analysis. J Kidney Cancer VHL. 2017;4(1):8-15.
  4. Motzer R, et al. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. The New England Journal of Medicine. 2018;378:1277-1290.
  5. Eichelberg C, Vervenne WL, De Santis M, et al. SWITCH: A randomised, sequential, open-label study to evaluate the efficacy and safety of sorafenib-sunitinib versus sunitinib-sorafenib in the treatment of metastatic renal cell cancer. Eur Urol. 2015;68;837-847.
  6. Motzer RJ, Barrios CH, Kim TM, et al. Phase II randomized trial comparing sequential first-line everolimus and second-line sunitinib versus first-line sunitinib and second-line everolimus in patients with metastatic renal cell carcinoma. J Clin Oncol. 2014;32:2765-2772.
  7. Ridge C, Pua B, Madoff D. Epidemiology and staging of renal cell carcinoma. Semin Intervent Radiol. 2014;31(1):3-8.
  8. Dolan DE, Gupta S. PD-1 pathway inhibitors: changing the landscape of cancer immunotherapy. Cancer Control. 2014;21(3):231-237.
  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.

SOURCE: EMD Serono

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