European Commission Approves Bavencio (avelumab) for Metastatic Merkel Cell Carcinoma
Not intended for UK-based media
- First approved immunotherapy for rare and aggressive skin cancer in the European Union, with initial launches planned in Germany and the UK
- Builds on Bavencio’s previous accelerated approvals in the US and recent approval in Switzerland
- Approval is based on data from the Javelin Merkel 200 study including durable tumor response rate and duration of response
Merck KGaA, Darmstadt, Germany and Pfizer Inc. (NYSE: PFE) today announced that the European Commission (EC) has granted marketing authorization for BAVENCIO® (avelumab) as a monotherapy for the treatment of adult patients with metastatic Merkel cell carcinoma (mMCC), a rare and aggressive skin cancer.1 BAVENCIO will have marketing authorization in the 28 countries of the European Union (EU) in addition to Norway, Liechtenstein and Iceland. BAVENCIO is expected to become commercially available to patients in Europe by prescription within the coming months, with initial launches in Germany and UK expected as early as October 2017.
“The EC’s decision is significant for BAVENCIO and more importantly, for European patients living with this very challenging skin cancer,” said Luciano Rossetti, M.D., Executive Vice President, Global Head of Research & Development at the biopharma business of Merck KGaA, Darmstadt, Germany. “Our alliance with Pfizer continues to demonstrate the power of working together, and we are grateful to everyone who has helped to bring the first and only approved immunotherapy for mMCC to European patients.”
“This European approval further establishes our continued momentum, building on the accelerated approvals BAVENCIO received in the US earlier this year,” said Liz Barrett, Global President, Pfizer Oncology. “Importantly, we are now one step closer to our goal of making BAVENCIO available to patients around the world.”
Approximately 2,500 Europeans are affected by MCC each year, with metastatic disease diagnosed in 5–12% of patients with MCC. Fewer than 20% of patients with metastatic MCC survive beyond 5 years.2-6
“Merkel cell carcinoma is a particularly aggressive form of skin cancer with very poor outcomes, especially for those with metastatic disease,” said Dirk Schadendorf, MD, Director of Dermatology, University Hospital Essen, Germany. “This approval is a meaningful development for patients and their families suffering from this devastating disease.”
The EC approval is based on data from JAVELIN Merkel 200, an international, multicenter, single-arm, open-label, Phase II study; with two parts:1
- Part A included 88 patients with mMCC whose disease had progressed after at least one chemotherapy treatment. The objective response rate was 33%, with 11% of patients experiencing a complete response and 22% of patients experiencing a partial response. At the time of analysis, tumor responses were durable, with 93% of responses lasting at least 6 months (n=25) and 71% of responses lasting at least 12 months (n=13). Duration of response (DOR) ranged from 2.8 to more than 24.9 months.
- Part B, at the time of the data cut-off, included 39 patients with histologically confirmed mMCC who were treatment-naïve to systemic therapy in the metastatic setting. The objective response rate was 62%, with 14% of patients experiencing a complete response (CR) and 48% of patients experiencing a partial response (PR). Sixty-seven percent of patients experienced a progression-free survival (PFS) rate of 3 months.
The safety of avelumab has been evaluated in 1,738 patients with solid tumours including metastatic MCC (N=88) receiving 10 mg/kg every 2 weeks of avelumab in clinical studies:1
- 1,738 patients with solid tumors received 10 mg/kg every 2 weeks. In this patient population, the most common adverse reactions were fatigue (32.4%), nausea (25.1%), diarrhea (18.9%), decreased appetite (18.4%), constipation (18.4%), infusion-related reactions (17.1%), weight decreased (16.6%), and vomiting (16.2%). The most common Grade ≥ 3 adverse reactions were anaemia (6.0%), dyspnoea (3.9%), and abdominal pain (3.0%). Serious adverse reactions were immune‑related adverse reactions and infusion‑related reaction.
The EC’s decision follows the US Food and Drug Administration’s (FDA) accelerated approval* for BAVENCIO earlier this year for the treatment of mMCC and patients with locally advanced or metastatic urothelial carcinoma (UC) who have disease progression during or following platinum-containing chemotherapy. BAVENCIO was also granted marketing authorization by Swissmedic on September 05, 2017, for the treatment of patients with mMCC, whose disease has progressed after at least one chemotherapy treatment.
The clinical development program for BAVENCIO, known as JAVELIN, involves at least 30 clinical programs and more than 6,300 patients evaluated across more than 15 different tumor types. In addition to mMCC, these cancers include breast, gastric/gastro-esophageal junction, head and neck, Hodgkin’s lymphoma, melanoma, mesothelioma, non-small cell lung, ovarian, renal cell carcinoma and urothelial carcinoma.
About Metastatic Merkel Cell Carcinoma
Metastatic MCC is a rare and aggressive disease in which cancer cells form in the top layer of the skin, close to nerve endings.7-8 MCC, which is also known as neuroendocrine carcinoma of the skin or trabecular cancer, often starts in those areas of skin that are most often exposed to the sun, including the head and neck, and arms.8,10 Risk factors for MCC include sun exposure and infection with Merkel cell polyomavirus. Caucasian males older than 50 are at increased risk.8,10 MCC is often misdiagnosed as other skin cancers and grows at an exponential rate on chronically sun-damaged skin.11-14 Current treatment options for MCC in Europe include surgery, radiation and chemotherapy.15 Treatment for metastatic or Stage IV MCC is generally palliative.16
About JAVELIN Merkel 200
The efficacy and safety of BAVENCIO was demonstrated in the JAVELIN Merkel 200 trial, a Phase II, open-label, single-arm, multicenter study, split into two parts:1
- Part A was conducted in 88 patients with histologically confirmed mMCC whose disease had progressed on or after chemotherapy administered for distant metastatic disease, with life expectancy of more than 3 months, and a minimum follow-up of 18 months. Overall in Part A, 59% of patients were reported to have had one prior anti-cancer therapy for mMCC and 41% had two or more prior therapies. The major efficacy outcome measures for Part A were confirmed best overall response (BOR) and DOR, according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, as assessed by a blinded independent endpoint review committee (IERC).
- Part B, at the time of the data cut-off, included 39 patients with histologically confirmed mMCC who were treatment-naïve to systemic therapy, 29 of whom had at least 13 weeks of follow-up. Enrollment in Part B of the study is ongoing and is planned to include 112 treatment-naïve patients. For Part B, the major efficacy outcome measure is durable response, defined as objective response (CR or PR) with a duration of at least 6 months; secondary outcome measures include BOR, DOR, PFS and overall survival (OS).
The trial excluded patients with active or a history of central nervous system (CNS) metastasis, prior treatment with anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibodies, active or a history of autoimmune disease, a history of other malignancies within the last 5 years, organ transplant, and conditions requiring therapeutic immune suppression or active infection with HIV, or hepatitis B or C. Patients received BAVENCIO 10 mg/kg as an intravenous infusion over 60 minutes every 2 weeks until disease progression or unacceptable toxicity.
BAVENCIO® (avelumab) is a human antibody specific for a protein called PD-L1, or programmed death ligand-1. BAVENCIO is designed to potentially engage both the adaptive and innate immune systems. By binding to PD-L1, BAVENCIO is thought to prevent tumor cells from using PD-L1 for protection against white blood cells, such as T cells, exposing them to anti-tumor responses. BAVENCIO has been shown to induce antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro. In November 2014, Merck KGaA, Darmstadt, Germany, and Pfizer announced a strategic alliance to co-develop and co-commercialize BAVENCIO.
*Indications in the US16
The US Food and Drug Administration (FDA) granted accelerated approval for BAVENCIO for the treatment of (i) mMCC in adults and pediatric patients 12 years and older and (ii) patients with locally advanced or metastatic urothelial carcinoma (UC) who have disease progression during or following platinum-containing chemotherapy, or who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. These indications were 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.
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 BAVENCIO for mMCC and patients with locally advanced or metastatic UC include fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, peripheral edema, decreased appetite/hypophagia, urinary tract infection and rash.
Alliance between Merck KGaA, Darmstadt, Germay, and Pfizer Inc., New York, US
Immuno-oncology is a top priority for Merck KGaA, Darmstadt, Germany, and Pfizer Inc. The global strategic alliance between Merck KGaA, Darmstadt, Germany, and Pfizer Inc., New York, US, 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 KGaA, Darmstadt, Germany. The immuno-oncology alliance will jointly develop and commercialize avelumab and advance 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 in 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 Merck KGaA, Darmstadt, Germany Website. Please go to www.emdgroup.com/subscribe to register online, change your selection or discontinue this service.
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, operates as EMD Serono, MilliporeSigma and EMD Performance Materials in the United States and Canada.
Pfizer Inc.: 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 healthcare products. Our global portfolio includes medicines and vaccines, as well as many of the world's best-known consumer healthcare 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, Pfizer has worked to make a difference for all who rely on us. To learn more, please visit us at www.pfizer.com. In addition, to learn more, follow us on Twitter at @Pfizer and @Pfizer_News, LinkedIn and like us on Facebook at Facebook.com/Pfizer.
Pfizer Disclosure Notice
The information contained in this release is as of September 20, 2017. 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 new indication in the EU as a monotherapy for the treatment of adult patients with metastatic Merkel cell carcinoma the Merck KGaA, Darmstadt, Germany-Pfizer Alliance involving anti-PD-L1 and anti-PD-1 therapies, 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 study commencement and completion dates and regulatory submission dates, as well as the possibility of unfavorable study results, including unfavorable new clinical data and additional analyses of existing clinical data; risks associated with interim data; the risk that clinical trial data are subject to differing interpretations, and, even when we view data as sufficient to support the safety and/or effectiveness of a product candidate, regulatory authorities may not share our views and may require additional data or may deny approval altogether; whether and when any other drug applications may be filed in any jurisdictions for potential indications for BAVENCIO, combination therapies or other product candidates; whether and when regulatory authorities in any other jurisdictions where applications are pending or may be submitted for BAVENCIO, combination therapies or other product candidates may approve any such applications, which will depend on the assessment by such regulatory authorities of the benefit-risk profile suggested by the totality of the efficacy and safety information submitted; decisions by regulatory authorities regarding labeling and other matters that could affect the availability or commercial potential of BAVENCIO, combination therapies or other product candidates; 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, 2016, 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.
- BAVENCIO® (avelumab) EU SmPC. Available from: http://www.ema.europa.eu/ema/: Accessed September 2017.
- Fitzgerald T et al. Dramatic increase in the incidence and mortality from Merkel cell carcinoma in the United States. Am Surg 2015;81(8):802-6.
- Stokes JB et al. Patients with Merkel cell carcinoma tumors < or = 1.0 cm in diameter are unlikely to harbor regional lymph node metastasis. J Clin Oncol 2009;27(23):3772–7.
- Allen PJ et al. Merkel cell carcinoma: prognosis and treatment of Patients from a single institution. J Clin Oncol 2005;23(10):2300–9.
- IMMOMEC (European Commission). Merkel Cell Carcinoma. Available from: http://www.immomec.eu/project/objectives/background/merkel-cell-carcinoma. Accessed September 2017.
- Lemos B et al. Pathologic Nodal Evaluation Improves Prognostic Accuracy in Merkel Cell Carcinoma: Analysis of 5,823 Cases as the Basis of the First Consensus Staging System for this Cancer. Journal of the American Academy of Dermatology. 2010;63:751–761.
- National Cancer Institute. Merkel Cell Carcinoma Treatment–Patient Version (PDQ®). Available from: https://www.cancer.gov/types/skin/patient/merkel-cell-treatment-pdq. Accessed September 2017.
- National Cancer Institute. Merkel Cell Carcinoma Treatment (PDQ®)–Health Professional Version. Available from: https://www.cancer.gov/types/skin/hp/merkel-cell-treatment-pdq. Accessed September 2017.
- American Cancer Society. Signs and Symptoms of Merkel Cell Carcinoma. Available from: http://www.cancer.org/cancer/skincancer-merkelcell/detailedguide/skin-cancer-merkel-cell-carcinoma-signs-and-symptoms. Accessed September 2017.
- Duprat J, Landman G, Salvajoli J and Brechtbühl E. A Review of the Epidemiology and Treatment of Merkel Cell Carcinoma. Clinics. 2011;66(10):1817–1823.
- Desch L and Kuntsfeld R. Merkel Cell Carcinoma: Chemotherapy and Emerging New Therapeutic Options. Journal of Skin Cancer. 2013:327150.
- Poulsen M. Merkel Cell Carcinoma of Skin: Diagnosis and Management Strategies. Drugs Aging. 2005;22(3):219–29.
- Swann MH and Yoon J. Merkel Cell Carcinoma. Seminars in Oncology. 2008;34(1):51–56.
- Heath M, Jaimes N and Lemos B. Clinical characteristics of Merkel cell carcinoma at diagnosis in 195 patients: the AEIOU features. J Am Acad Dermatol 2008;58:375–81. http://www.pnlab.org/clinical/documents/ClinCharacteristics.pdf.
Accessed September 2017.
- American Cancer Society. What is Merkel cell carcinoma? Available from: http://www.cancer.org/cancer/skincancer-merkelcell/detailedguide/skin-cancer-merkel-cell-carcinoma-what-is-merkel-cell-carcinoma. Accessed September 2017.
- BAVENCIO Prescribing Information. 2017. Rockland, MA: EMD Serono Inc.
Based on high demand expected to continue throughout the year and a very strong first quarter of 2021 with net sales of EUR 4.63 bn resulting in EBITDA pre of EUR 1.51 bn and EPS pre of EUR 2.18, ...