DARMSTADT, Germany and NEW YORK, July
20, 2017 /PRNewswire/ --
Not intended for 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 the EC is expected in the third quarter of 2017
Merck KGaA, Darmstadt, Germany, which operates its biopharmaceutical business as EMD Serono
in the US and Canada, 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®) 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, which 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 KGaA, Darmstadt, Germany. "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 treatment 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 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 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® 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, an international, multicenter,
single-arm, open-label, Phase II 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 KGaA, Darmstadt, Germany, 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®) 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
BAVENCIO can cause immune-mediated pneumonitis, including fatal cases. Monitor patients for signs and symptoms of
pneumonitis and evaluate suspected cases with radiographic imaging. Administer corticosteroids for Grade 2 or greater
pneumonitis. Withhold BAVENCIO for moderate (Grade 2) and permanently discontinue for severe (Grade 3), life-threatening (Grade
4), or recurrent moderate (Grade 2) pneumonitis. Pneumonitis occurred in 1.2% (21/1738) of patients, including one (0.1%) patient
with Grade 5, one (0.1%) with Grade 4, and five (0.3%) with Grade 3.
BAVENCIO can cause immune-mediated hepatitis, including fatal cases. Monitor patients for abnormal liver tests
prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater hepatitis. Withhold BAVENCIO for
moderate (Grade 2) immune-mediated hepatitis until resolution and permanently discontinue for severe (Grade 3) or
life-threatening (Grade 4) immune-mediated hepatitis. Immune-mediated hepatitis was reported in 0.9% (16/1738) of patients,
including two (0.1%) patients with Grade 5 and 11 (0.6%) with Grade 3.
BAVENCIO can cause immune-mediated colitis. Monitor patients for signs and symptoms of colitis. Administer
corticosteroids for Grade 2 or greater colitis. Withhold BAVENCIO until resolution for moderate or severe (Grade 2 or 3)
colitis and permanently discontinue for life-threatening (Grade 4) or recurrent (Grade 3) colitis upon re-initiation of BAVENCIO.
Immune-mediated colitis occurred in 1.5% (26/1738) of patients, including seven (0.4%) with Grade 3.
BAVENCIO can cause immune-mediated endocrinopathies, including adrenal insufficiency, thyroid disorders, and type
1 diabetes mellitus.
Monitor patients for signs and symptoms of adrenal insufficiency during and after treatment, and administer
corticosteroids as appropriate. Withhold BAVENCIO for severe (Grade 3) or life-threatening (Grade 4) adrenal insufficiency.
Adrenal insufficiency was reported in 0.5% (8/1738) of patients, including one (0.1%) with Grade 3.
Thyroid disorders can occur at any time during treatment. Monitor patients for changes in thyroid function at the
start of treatment, periodically during treatment, and as indicated based on clinical evaluation. Manage hypothyroidism with
hormone replacement therapy and hyperthyroidism with medical management. Withhold BAVENCIO for severe (Grade 3) or life-
threatening (Grade 4) thyroid disorders. Thyroid disorders including hypothyroidism, hyperthyroidism, and thyroiditis were
reported in 6% (98/1738) of patients, including three (0.2%) with Grade 3.
Type 1 diabetes mellitus including diabetic ketoacidosis: Monitor patients for hyperglycemia or other signs and
symptoms of diabetes. Withhold BAVENCIO and administer anti-hyperglycemics or insulin in patients with severe or life-threatening
(Grade ≥ 3) hyperglycemia, and resume treatment when metabolic control is achieved. Type 1 diabetes mellitus without an
alternative etiology occurred in 0.1% (2/1738) of patients, including two cases of Grade 3 hyperglycemia.
BAVENCIO can cause immune-mediated nephritis and renal dysfunction. Monitor patients for elevated serum creatinine
prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater nephritis. Withhold BAVENCIO for
moderate (Grade 2) or severe (Grade 3) nephritis until resolution to Grade 1 or lower. Permanently discontinue BAVENCIO for
life-threatening (Grade 4) nephritis. Immune-mediated nephritis occurred in 0.1% (1/1738) of patients.
BAVENCIO can result in other severe and fatal immune-mediated adverse reactions involving any organ system
during treatment or after treatment discontinuation. For suspected immune-mediated adverse reactions, evaluate to confirm or rule
out an immune-mediated adverse reaction and to exclude other causes. Depending on the severity of the adverse reaction, withhold
or permanently discontinue BAVENCIO, administer high-dose corticosteroids, and initiate hormone replacement therapy if
appropriate. Resume BAVENCIO when the immune-mediated adverse reaction remains at Grade 1 or lower following a corticosteroid
taper. Permanently discontinue BAVENCIO for any severe (Grade 3) immune-mediated adverse reaction that recurs and for any
life-threatening (Grade 4) immune-mediated adverse reaction. The following clinically significant immune-mediated adverse
reactions occurred in less than 1% of 1738 patients treated with BAVENCIO: myocarditis with fatal cases, myositis, psoriasis,
arthritis, exfoliative dermatitis, erythema multiforme, pemphigoid, hypopituitarism, uveitis, Guillain-Barré syndrome, and
systemic inflammatory response.
BAVENCIO can cause severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions. Patients
should be premedicated with an antihistamine and acetaminophen prior to the first 4 infusions and for subsequent doses based upon
clinical judgment and presence/severity of prior infusion reactions. Monitor patients for signs and symptoms of
infusion-related reactions, including pyrexia, chills, flushing, hypotension, dyspnea, wheezing, back pain, abdominal pain, and
urticaria. Interrupt or slow the rate of infusion for mild (Grade 1) or moderate (Grade 2) infusion-related reactions.
Permanently discontinue BAVENCIO for severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions. Infusion-related
reactions occurred in 25% (439/1738) of patients, including three (0.2%) patients with Grade 4 and nine (0.5%)
with Grade 3.
BAVENCIO can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to a fetus
including the risk of fetal death. Advise females of childbearing potential to use effective contraception during treatment with
BAVENCIO and for at least 1 month after the last dose of BAVENCIO. It is not known whether BAVENCIO is excreted in human milk.
Advise a lactating woman not to breastfeed during treatment and for at least 1 month after the last dose of BAVENCIO due
to the potential for serious adverse reactions in breastfed infants.
T he most common adverse reactions (all grades, ≥ 20%) in patients with metastatic Merkel cell carcinoma
(MCC) were fatigue (50%), musculoskeletal pain (32%), diarrhea (23%), nausea (22%), infusion-related reaction (22%), rash
(22%), decreased appetite (20%), and peripheral edema (20%).
Selected treatment-emergent laboratory abnormalities (all grades, ≥ 20%) in patients with metastatic MCC were
lymphopenia (49%), anemia (35%), increased aspartate aminotransferase (34%), thrombocytopenia (27%), and increased alanine
aminotransferase (20%).
The most common adverse reactions (all grades, ≥ 20%) in patients with locally advanced or metastatic urothelial
cancer (UC) were fatigue (41%), infusion-related reaction (30%), musculoskeletal pain (25%), nausea (24%), decreased
appetite/hypophagia (21%) and urinary tract infection (21%).
Selected laboratory abnormalities (grades 3-4, ≥ 3%) in patients with locally advanced or metastatic UC were
hyponatremia (16%), gamma-glutamyltransferase increased (12%), lymphopenia (11%), hyperglycemia (9%), increased alkaline
phosphatase (7%), anemia (6%), increased lipase (6%), hyperkalemia (3%), and increased aspartate aminotransferase (3%).
Please see full US Prescribing
Information and Medication Guide.
Alliance between Merck KGaA, Darmstadt, Germany, and Pfizer Inc., New York, US
Immuno-oncology is a top priority for Merck KGaA, Darmstadt, Germany, and Pfizer Inc. The
global strategic alliance between Merck KGaA, Darmstadt, Germany, and Pfizer Inc., New York, US, enables the companies to benefit from each other's strengths and capabilities and further
explore the therapeutic potential of avelumab, an anti-PD-L1 antibody initially discovered and developed by Merck KGaA,
Darmstadt, Germany. 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 in combination regimens, and is striving to find new ways to treat cancer.
All Merck KGaA, Darmstadt, Germany Press Releases are distributed by e-mail at the same time they become available on the
Merck KGaA, Darmstadt, Germany Website. Please go to http://www.emdgroup.com/subscribe to register online, change your selection or discontinue this service.
About Merck KGaA, Darmstadt, Germany
Merck KGaA, Darmstadt, Germany, 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 scientific research and
production, to liquid crystals for smartphones and LCD televisions. In 2016, Merck KGaA, Darmstadt, Germany, generated sales of €15.0 billion in 66 countries.
Founded in 1668, Merck KGaA, Darmstadt, Germany, is the world's oldest pharmaceutical and
chemical company. The founding family remains the majority owner of the publicly listed corporate group. Merck KGaA, Darmstadt,
Germany, operates as EMD Serono, MilliporeSigma and EMD Performance Materials in the United States and Canada.
Pfizer Inc.: Working together for a healthier world ®
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 manufacture of healthcare
products. Our global portfolio includes medicines and vaccines, as well as many of the world's best-known consumer healthcare
products. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and
cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier
innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support
and expand access to reliable, affordable health care around the world. For more than 150 years, Pfizer has worked to make a
difference for all who rely on us. To learn more, please visit us at http://www.pfizer.com. In addition, to learn more, follow us on Twitter at @Pfizer and @Pfizer_News, LinkedIn
and like us on Facebook at Facebook.com/Pfizer.
Pfizer Disclosure Notice
The information contained in this release is as of July 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 potential indication in the EU as a
monotherapy for the treatment of adult patients with metastatic Merkel cell carcinoma (the "potential indication"), the Merck
KGaA, Darmstadt, Germany-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 of which are filed with the U.S. Securities and Exchange Commission and available
at http://www.sec.gov and http://www.pfizer.com.
References
- BAVENCIO Prescribing Information. Rockland, MA: EMD Serono Inc.; 2017.
- Schadendorf D et al. Merkel cell carcinoma: epidemiology, prognosis, therapy and unmet medical needs. European Journal of
Cancer 2017;71;53-69
- 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.
- 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.
- 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.
- NCCN Merkel Cell Carcinoma Guidelines version I. 2017. http://www.nccn.org/professionals/physician_gls/PDF/mcc.pdf. Last accessed June
2017.
Your Contacts
Merck KGaA, Darmstadt, Germany
Media
Friederike Segeberg
+49-6151-72-6328
Investor Relations
+49-6151-72-3321
Pfizer
Media (US)
Sally Beatty
+1-212-733-6566
Media (EU)
Dervila Keane
+353 86 2110834
Investor Relations
Ryan Crowe
+1-212-733-8160
(Logo: http://mma.prnewswire.com/media/512993/Merck_KGaA_Pfizer_Logo.jpg )
SOURCE Merck KGaA, Darmstadt, Germany