FDA Accepts the Biologics License Application for Avelumab for the Treatment of Metastatic Merkel Cell Carcinoma for Priority Review

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DARMSTADT, Germany and NEW YORK, Nov. 29, 2016 /PRNewswire=KYODO JBN/ --

     Not intended for UK-based media

    - If approved by the FDA, avelumab, an investigational immunotherapy, could

be the first treatment indicated for patients with metastatic Merkel cell

carcinoma (MCC)

    - Avelumab has previously received FDA Breakthrough Therapy and Fast Track

Designations for metastatic MCC, as well as FDA Orphan Drug Designation for MCC

    Merck and Pfizer Inc. (NYSE: PFE) today announced that the US Food and Drug

Administration (FDA) has accepted for Priority Review the Biologics License

Application (BLA) for avelumab, which was submitted by EMD Serono, the

biopharmaceutical business of Merck in the US and Canada. This review relates

to avelumab's proposed use in patients with metastatic Merkel cell carcinoma

(MCC), based on tumor response results from the JAVELIN Merkel 200 trial.

Avelumab is an investigational fully human anti-PD-L1 IgG1 monoclonal antibody

and could be the first treatment indicated for metastatic MCC in the US, if

approved.* MCC is a rare and aggressive skin cancer, which impacts

approximately 2,500 Americans a year.[1],[2]

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    "We are pleased the FDA has granted a Priority Review designation for

avelumab," said Luciano Rossetti, M.D., Executive Vice President, Global Head

of Research & Development at the biopharma business of Merck. "There are

currently no approved treatment options for metastatic MCC, and we are

committed to working with the FDA to potentially bring the first approved

cancer immunotherapy to patients with this aggressive disease."

    The avelumab metastatic MCC BLA submission is supported by data from

JAVELIN Merkel 200, a multicenter, single-arm, open-label, Phase II study of 88

patients with metastatic MCC, whose disease had progressed after at least one

chemotherapy treatment.[1] The JAVELIN Merkel 200 study represents the largest

data set of any anti-PD-L1/PD-1 antibody reported in this patient population.

These data were presented in June 2016 at the Annual Meeting of the American

Society of Clinical Oncology (ASCO) and published in the Lancet Oncology in

October 2016.[1]

    "Metastatic Merkel cell carcinoma is an aggressive disease, and patients

face a very poor prognosis, with less than 20 percent surviving beyond five

years," said Chris Boshoff,  M.D., Ph.D., Senior Vice President and Head of

Immuno-oncology, Early Development and Translational Oncology, Pfizer Global

Product Development. "We are encouraged by the results of our Phase II trial

and believe avelumab may have potential to be an important treatment option for

patients living with this hard-to-treat skin cancer."

    The FDA's Priority Review status reduces the review time from 10 months to

a goal of six months from the day of filing and is given to drugs that may

offer major advances in treatment or may provide a treatment where no adequate

therapy exists. The FDA previously granted avelumab Orphan Drug Designation for

MCC, as well as Fast Track and Breakthrough Therapy Designations for the

treatment of patients with metastatic MCC whose disease has progressed after at

least one previous chemotherapy regimen. Breakthrough Therapy Designation is

intended to expedite the development and review of treatments for serious or

life-threatening disease where preliminary clinical evidence indicates that the

drug may demonstrate substantial improvement over existing therapies for one or

more endpoints. [3] Additionally, the European Medicines Agency has validated

for review Merck's Marketing Authorization Application (MAA) for avelumab, for

the proposed indication of metastatic MCC.

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

at least 30 clinical programs and more than 3,000 patients evaluated across

more than 15 different tumor types. In addition to metastatic MCC, these

cancers include breast, gastric/gastroesophageal junction, head and neck,

Hodgkin's lymphoma, melanoma, mesothelioma, non-small cell lung, ovarian, renal

cell carcinoma and urothelial (primarily bladder).

    *Avelumab is not approved for any indication in any market. This marks the

first acceptance of an application by the US FDA to review the investigational

product, avelumab.

    About Metastatic Merkel Cell Carcinoma (MCC)

    Metastatic MCC is a rare and aggressive disease in which cancer cells form

in the top layer of the skin, close to nerve endings.[1],[4] 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.[5] Risk factors for MCC include sun exposure and

having 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 at higher risk). Caucasian males older than 50 are at increased

risk.[5] MCC is often misdiagnosed for other skin cancers and grows at an

exponential rate on chronically sun-damaged skin.[6]-[9] Current treatment

options for MCC include surgery, radiation and chemotherapy.[10] Treatment for

metastatic or Stage IV MCC is generally palliative.

    About Avelumab

    Avelumab (also known as MSB0010718C) is an investigational, fully human

anti-PD-L1 IgG1 monoclonal antibody. By inhibiting PD-L1 interactions, avelumab

is thought to enable the activation of T-cells and the adaptive immune system.

By retaining a native Fc-region, avelumab is thought to potentially engage the

innate immune system and induce antibody-dependent cell-mediated cytotoxicity

(ADCC). In November 2014, Merck and Pfizer announced a strategic alliance to

co-develop and co-commercialize avelumab. In the JAVELIN Merkel 200 trial,

treatment-related adverse events (AEs) occurred in 62 (70%) of 88 patients

including fatigue and infusion-related reactions. Five grade 3

treatment-related AEs were reported in four of 88 patients and include two

patients with lymphopenia and three patients with isolated laboratory

abnormalities (elevated blood creatine phosphokinase, blood cholesterol, and

hepatic aminotransferase).[1] There were no grade 4 treatment-related AEs or

deaths related to treatment.[1]

    About EMD Serono, Inc.

    EMD Serono is the biopharmaceutical business of Merck in the US and Canada

- a leading science and technology company - focused exclusively on specialty

care. For more than 40 years, the business has integrated cutting-edge science,

innovative products and industry-leading patient support and access programs.

EMD Serono has deep expertise in neurology, fertility and endocrinology, as

well as a robust pipeline of potential therapies in oncology, immuno-oncology

and immunology as R&D focus areas. Today, the business has 1,200 employees

around the country with commercial, clinical and research operations based in

the company's home state of Massachusetts. www.emdserono.com

[http://www.emdserono.com ]

    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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visit www.merckgroup.com/en/media/media_center_oncology.html

[http://www.merckgroup.com/en/media/media_center_oncology.html ]

    About Merck

    Merck 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

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televisions. In 2015, Merck generated sales of EUR 12.85 billion in 66

countries.

    Founded in 1668, Merck is the world's oldest pharmaceutical and chemical

company. The founding family remains the majority owner of the publicly listed

corporate group. Merck, Darmstadt, Germany holds the global rights to the Merck

name and brand. The only exceptions are the United States and Canada, where the

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

    Pfizer Inc.: Working together for a healthier world(R)

    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

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the most feared diseases of our time. Consistent with our responsibility as one

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    Pfizer Disclosure Notice

    The information contained in this release is as of November 29, 2016.

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 avelumab

(MSB0010718C), including a potential indication for avelumab for the treatment

of metastatic Merkel Cell carcinoma (the "Potential Indication"), Pfizer's and

Merck's immuno-oncology 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, the uncertainties inherent in

research and development, including the ability to meet anticipated clinical

study commencement and completion dates as well as the possibility of

unfavorable study results; 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 drug

applications may be filed in other jurisdictions the Potential Indication or

whether and when drug applications may be filed in any jurisdictions for any

other potential indications for avelumab, combination therapies or other

product candidates; whether and when the BLA or MAA for the Potential

Indication or any such applications may be approved by regulatory authorities,

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

avelumab, 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, 2015, 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

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    References

＜start_indent＞

    1) Kaufman HL, et al. Avelumab in patients with chemotherapy-refractory

metastatic Merkel cell carcinoma: a multicentre, single-group, open-label,

phase 2 trial. Lancet Oncology. 2016;17(10);1374-85.

    2) Fitzgerald T et al. Dramatic increase in the incidence and mortality

from Merkel cell carcinoma in the United States. The American Journal of

Surgery. 2015;81(8):802-6.

    3) FDA. Priority Review.

http://www.fda.gov/ForPatients/Approvals/Fast/ucm405405.htm. Last accessed

October 2016.

    4) National Cancer Institute. Merkel cell carcinoma treatment-patient

version (PDQ(R)).

http://www.cancer.gov/types/skin/patient/merkel-cell-treatment-pdq. Last

accessed October 2016. 5) 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

[http://www.cancer.org/cancer/skincancer-merkelcell/detailedguide/skin-cancer-me

rkel-cell-carcinoma-what-is-merkel-cell-carcinoma.%20Last%20accessed%20October%2

02016 ]. Last accessed October 2016.

    6) Desch L and Kuntsfeld R. Merkel cell carcinoma: chemotherapy and

emerging new therapeutic options. Journal of Skin Cancer. 2013(2013):327150.

    7) 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.

    8) Poulsen M. Merkel cell carcinoma of skin: diagnosis and management

strategies. Drugs Aging. 2005;22(3):219-29.

    9) Swann MH and Yoon J. Merkel cell carcinoma. Seminars in Oncology.

2008;34(1):51-56.   

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

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

October 2016.

  SOURCE: Merck