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.