EMA's CHMP Issues Positive Opinion for Avelumab for the Treatment of Metastatic Merkel Cell Carcinoma

PR69405

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

    Not intended for US, Canadian and UK-based media

    - If approved, avelumab could be the first immunotherapy treatment

indicated for this rare and aggressive skin cancer in the EU

    - Decision by EC is expected in the third quarter of 2017

    Merck and Pfizer Inc. (NYSE: PFE) today announced that the Committee for

Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA)

has recommended the approval of avelumab* (BAVENCIO(R)) as a monotherapy for

the treatment of adult patients with metastatic Merkel cell carcinoma (mMCC), a

rare and aggressive skin cancer. The European Commission (EC) will now review

the CHMP's recommendation, with a decision expected in the third quarter of

2017.

    "We welcome the CHMP's recommendation, as there are currently no approved

treatments in Europe for this type of skin cancer that can be devastating for

patients and their families," said Luciano Rossetti, M.D., Executive Vice

President, Global Head of Research & Development at the biopharma business of

Merck. "This is an important step towards making avelumab available to patients

and we look forward to the European Commission's decision later this year."

    "Metastatic Merkel cell carcinoma is a devastating disease and patients in

Europe currently have very few options," said Chris Boshoff, M.D., PhD, Senior

Vice President and Head of Immuno-Oncology, Early Development, Translational

Oncology, Pfizer Global Product Development. "This milestone further

demonstrates our commitment to tackle hard-to-treat cancers as we continue to

explore the potential of avelumab in other tumors."

    The CHMP positive opinion is based on data from JAVELIN Merkel 200, an

international, multicenter, single-arm, open-label, Phase II study split into

two parts:

    - Part A included 88 patients with mMCC whose disease had progressed after

at least one chemotherapy treatment, with 59% of patients reported to have had

one prior anti-cancer therapy for mMCC and 41% had two or more prior therapies.

Data submitted included a minimum of 18 months of follow-up.

    - 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, 29 of whom had at least 13 weeks of follow-up.

Enrolment in Part B of the study is ongoing and is planned to include 112

treatment-naïve patients.  

    The human anti-PD-L1 antibody, avelumab, previously received Orphan Drug

Designation (ODD) from the EC for MCC. To qualify for ODD in the EU, a medicine

must be intended for the treatment, prevention or diagnosis of a disease that

is life-threatening or chronically debilitating, and has a prevalence in the EU

of not more than 5 in 10,000 people.

    The US Food and Drug Administration (FDA) granted accelerated approval for

avelumab in March 2017 for the treatment of mMCC in adults and pediatric

patients aged 12 years and older; and in May 2017 for the treatment of patients

with locally advanced or metastatic urothelial carcinoma who have disease

progression during or following platinum-containing chemotherapy therapy, or

who have disease progression within 12 months of neoadjuvant or adjuvant

treatment with platinum-containing chemotherapy.[1] These indications were

granted under accelerated approval based on tumor response rate and duration of

response

data/criteria. Continued approval for these indications may be contingent upon

verification and description of clinical benefit in confirmatory trials.

    The clinical development program for avelumab, known as JAVELIN, involves

at least 30 clinical programs and more than 6,000 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.

    * Avelumab is not approved for any indication in any market outside the US.

BAVENCIO(R) is the proprietary name submitted to EMA for the investigational

medicine avelumab.

    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.[2],[3] 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.[2],[4] Risk factors for MCC include sun exposure

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

at increased risk.[2],[4] MCC is a highly immunogenic cancer, meaning that

those with a weak immune system (i.e., solid organ transplant recipients,

people with HIV/AIDS and people with other cancers, such as chronic lymphocytic

leukemia) are also at a higher risk.[2],[4] MCC is often misdiagnosed for other

skin cancers and grows at an exponential rate on chronically sun-damaged

skin.[4]-[6]

Current treatment options for MCC in Europe include surgery, radiation and

chemotherapy.[3] Treatment for metastatic or Stage IV MCC is generally

palliative.[3]

    About JAVELIN Merkel 200

    The efficacy and safety of avelumab was demonstrated in the JAVELIN Merkel

200 trial, a Phase II, open-label, single-arm, multicenter study, split into

two parts:

    - 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. 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. Data submitted included a minimum

of 18 months follow-up. The major efficacy outcome measures for Part A were

confirmed best overall response (BOR) and duration of response (DOR), according

to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, as assessed by a

blinded independent endpoint review committee (IERC); secondary efficacy

outcome measures included duration of response (DOR), and progression-free

survival (PFS).

    - 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, 29 of whom had at least 13 weeks of follow-up.

Enrolment in Part B of the study is ongoing and is planned to include 112

treatment-naïve patients. The major efficacy outcome measure is durable

response, defined as objective response (complete response [CR] or partial

response [PR]) with a duration of at least 6 months; secondary outcome measures

include BOR, DOR, progression-free survival (PFS) and overall survival (OS).

    The trial excluded patients with active or a history of central nervous

system (CNS) metastasis, 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 avelumab 10 mg/kg as an intravenous

infusion over 60 minutes every 2 weeks until disease progression or

unacceptable toxicity.

    About Avelumab

    Avelumab is a human antibody specific for a protein called PD-L1, or

programmed death ligand-1. Avelumab is designed to potentially engage both the

adaptive and innate immune systems. By binding to PD-L1, avelumab 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. Avelumab 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 avelumab.

    Indications

    The US Food and Drug Administration (FDA) granted accelerated approval for

avelumab (BAVENCIO(R)) for the treatment of (i) mMCC in adults and pediatric

patients 12 years and older and (ii) patients with locally advanced or

metastatic 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

    The warnings and precautions for avelumab (BAVENCIO(R)) 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 avelumab 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 avelumab, an investigational anti-PD-L1 antibody

initially discovered and developed by Merck. 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 combination

regimens, and

is striving to find new ways to treat cancer.

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company operates as EMD Serono, MilliporeSigma and EMD Performance Materials.

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    Pfizer Disclosure Notice

    The information contained in this release is as of [INSERT DATE], 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 potential indication in the EU as a monotherapy for the

treatment of adult patients with metastatic Merkel cell carcinoma (the

"potential indication"), 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 the European Commission may approve

the pending marketing authorization application for the potential indication

and 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

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    References

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

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

       therapy and unmet medical needs. European Journal of Cancer 2017;71;53-69

    3) American Cancer Society. What is Merkel cell carcinoma?

http://www.cancer.org/cancer/skincancer-merkelcell/detailedguide/skin-cancer-merkel-cell-carcinoma-what-is-merkel-cell-carcinoma

      . Last accessed June 2017.

    4) 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.

    5) 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. Last

       accessed June 2017.

    6) NCCN Merkel Cell Carcinoma Guidelines version I. 2017.

       http://www.nccn.org/professionals/physician_gls/PDF/mcc.pdf. Last

       accessed June 2017.

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