European Commission Approves Bavencio (avelumab) for Metastatic Merkel Cell Carcinoma

PR70196

DARMSTADT, Germany, and NEW YORK, Sept. 21, 2017 /PRNewswire=KYODO JBN/ --

      Not intended for US, Canadian and 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 and Pfizer Inc. (NYSE: PFE) today announced that the European

Commission (EC) has granted marketing authorization for BAVENCIO(R) (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. "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-naive 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 greater than or equal to 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.[7],[9] Risk factors for MCC include sun exposure

and infection with Merkel cell polyomavirus. Caucasian males older than 50 are

at increased risk.[7],[9] MCC is often misdiagnosed as other skin cancers and

grows at an exponential rate on chronically sun-damaged skin.[9-11] Current

treatment options for MCC in Europe include surgery, radiation and chemotherapy.

[8] Treatment for metastatic or Stage IV MCC is generally palliative.[8]

    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-naive 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-naive 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.

    About BAVENCIO  

BAVENCIO(R) (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 and Pfizer announced a strategic alliance to

co-develop and co-commercialize BAVENCIO.

    *Indications in the US[12]

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.

    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 BAVENCIO, an investigational anti-PD-L1 antibody initially

discovered and developed by Merck. The immuno-oncology alliance will jointly

develop and commercialize BAVENCIO and advance Pfizer's PD-1 antibody. 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.

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    Pfizer Disclosure Notice  

The information contained in this release is as of September 21, 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 Europe as a monotherapy for the

treatment of adult patients with metastatic Merkel cell carcinoma, the

Merck-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 http://www.sec.gov and www.pfizer.com

[http://www.pfizer.com ].

    References    

    

    1) BAVENCIO(R) (avelumab) EU SmPC. Available

from: http://www.ema.europa.eu/ema:

      Accessed September 2017.

    2) 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.

    3) 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.

    4) Allen PJ et al. Merkel cell carcinoma: prognosis and treatment of

Patients from a single institution. J Clin Oncol 2005;23(10):2300-9.

    5) IMMOMEC (European Commission). Merkel Cell Carcinoma. Available

      

from: http://www.immomec.eu/project/objectives/background/merkel-cell-carcinoma.

Accessed September 2017

[http://www.immomec.eu/project/objectives/background/merkel-cell-carcinoma.%20Ac

cessed%20September%202017 ].

    6) 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.

    7) Schadendorf D et al. Merkel cell carcinoma: epidemiology,

      prognosis, therapy and unmet medical needs. European Journal of Cancer

2017;71;53-69

    8) American Cancer Society. What is Merkel cell carcinoma? Available

      

from: http://www.cancer.org/cancer/skincancer-merkelcell/detailedguide/skin-canc

er-merkel-cell-carcinoma-what-is-merkel-cell-carcinoma. Accessed September

2017.

    9) Nghiem P. Systematic literature review of efficacy, safety and

tolerability outcomes of chemotherapy regimens in patients with metastatic

Merkel cell carcinoma. Future Oncology 2017;13(14):1263-1279.

      10) Heath M, Jaimes N and Lemos B. Clinical characteristics of Merkel

cell carcinoma at diagnosis in 195 patients: the AEIOU features. Journal of the

American Academy of Dermatology

2008;58:375-81. http://www.pnlab.org/clinical/documents/ClinCharacteristics.pdf.

      Accessed September 2017.

      11) NCCN Merkel Cell Carcinoma Guidelines version I.

      2017. www.nccn.org/professionals/physician_gls/PDF/mcc.pdf. Last accessed

June 2017     

[http://www.nccn.org/professionals/physician_gls/PDF/mcc.pdf.%20Last%20accessed%

20June%202017 ]

      .

      12) BAVENCIO Prescribing Information. 2017. Rockland, MA: EMD Serono Inc.

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