European Medicines Agency Validates the Marketing Authorization Application for Avelumab for the Treatment of Metastatic Merkel Cell Carcinoma

PR66346

DARMSTADT, Germany and NEW YORK, Oct. 31, 2016/PRNewswire=KYODO JBN/ --

- Not intended for UK-based media

- If approved, avelumab, an investigational anti-PD-L1 IgG1, could be the first

treatment indicated for patients with metastatic Merkel cell carcinoma  

- The Marketing Authorization Application is based on Phase II data from the

JAVELIN Merkel 200 study demonstrating meaningful tumor responses in patients

with metastatic disease that progressed after prior chemotherapy   

- JAVELIN Merkel 200 is the largest reported anti-PD-L1/PD-1 antibody study in

this patient population   

Merck and Pfizer Inc. (NYSE: PFE) today announced that the European Medicines

Agency (EMA) has validated for review Merck's Marketing Authorization

Application (MAA) for avelumab, for the proposed indication of metastatic

Merkel cell carcinoma (MCC), a rare and aggressive skin cancer, which impacts

approximately 2,500 Europeans a year.[1],[2] Validation of the MAA confirms

that submission is complete and begins the EMA's centralized review process.*

If approved, avelumab, an investigational fully human anti-PD-L1 IgG1

monoclonal antibody, could be the first approved treatment indicated for

metastatic MCC in the EU. Patients with metastatic MCC face a very poor

prognosis, with less than 20 percent surviving beyond five years.[3]

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"While early-stage Merkel cell carcinoma can be generally managed with surgery,

there are significant unmet needs in metastatic disease, where treatment

options are severely limited," said Luciano Rossetti, M.D., Executive Vice

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

Merck. "We are pleased that the EMA is initiating its review of avelumab, as

this means we are one step closer to bringing a much-needed new treatment

option to European patients."

"This is the first of what we hope will be many regulatory milestones for

avelumab," 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 committed to evaluating avelumab in a number of

hard-to-treat cancers, and we believe it may have potential to be an important

treatment option for patients with metastatic Merkel cell carcinoma."

The avelumab metastatic MCC MAA 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 recently published in the Lancet Oncology.[1]

Avelumab received an Orphan Drug Designation (ODD) from the European Commission

for MCC. To qualify for an 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; the prevalence of the condition in the EU must not be

more than 5 in 10,000, or it must be unlikely that marketing of the medicine

would generate sufficient returns to justify the investment needed for its

development; and it must be for a disease where no satisfactory treatment is

currently available.[4]

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

least 30 clinical programs and over 2,900 patients evaluated across more than

15 different tumor types. In addition to metastatic MCC, 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 (primarily bladder).

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

first acceptance of an EU market authorization application to review the safety

and efficacy results for the investigational product avelumab.

References

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. IMMOMEC (European Commission). Merkel Cell Carcinoma.

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

Last accessed October 2016.

3. 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.

4. European Medicines Agency. Orphan designation.

http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000029.jsp.

Last accessed October 2016.

5. 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.

6. 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 October 2016.

7. Desch L and Kuntsfeld R. Merkel cell carcinoma: chemotherapy and emerging

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

http://dx.doi.org/10.1155/2013/327150

8. 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

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

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

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

2008;34(1):51-56.

11. NCCN Merkel Cell Carcinoma Guidelines version I. 2017.

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

October 2016.

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],[5] 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.[6] 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. [7]-[10] Current treatment

options for MCC include surgery, radiation and chemotherapy.[8]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 KGaA, Darmstadt, Germany, 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] No patients in the trial discontinued treatment

with avelumab permanently due to AEs; however, AEs leading to temporary

treatment discontinuation of avelumab were anemia, diarrhea, and increased ALT

in one patient each.[1]

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

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

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

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

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people that extend and significantly improve their lives. We strive to set the

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Pfizer Disclosure Notice  

The information contained in this release is as of October 31, 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 Indications"), 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 for 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 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

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