DARMSTADT, Germany and
NEW YORK, USA, September 21, 2017 /PRNewswire/ --
Not intended for 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 based on data from
Javelin Merkel 200 study
including durable tumor
response rate and duration of
response
Merck KGaA, Darmstadt, Germany,
and Pfizer Inc. (NYSE: PFE) today announced that the European
Commission (EC) has granted marketing authorization for
BAVENCIO® (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 KGaA,
Darmstadt, Germany, which operates
as EMD Serono in the US and Canada. "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-naïve 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 ≥ 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, in Switzerland 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, emelanoma,
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-naïve 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-naïve 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 metastasis (CNS), 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® (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 KGaA, Darmstadt, Germany 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
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
antihyperglycemics or insulin in patients with severe or
life-threatening (Grade 3 equal to or greater) 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 one month after the last
dose of BAVENCIO. It is not known whether BAVENCIO is excreted in
human milk. Advise a lactating woman not to
breastfeedduring treatment and for at least one month after the
last dose of BAVENCIO due to the potential for serious adverse
reactions in breastfed infants.
The most common adverse reactions (all grades,
greater than or equal to 20%) in patients
with metastatic Merkel cell carcinoma (MCC) were
fatigue (50%), musculoskeletal pain (32%), diarrhea (23%), nausea
(22%), infusion-related reactions (22%), rash (22%), decreased
appetite (20%), and peripheral edema (20%).
Selected treatment-emergent laboratory
abnormalities (all grades, greater than or equal to 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
greater than or equal to 20%) in patients with locally
advanced or metastatic urothelial carcinoma
(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,
greater than or equal to 3%) inpatients with locally
advanced or metastatic UC were hyponatremia
(16%), increased gamma-glutamyltransferase (12%), lymphopenia
(11%), hyperglycemia (9%), increased alkaline phosphatatse (7%),
anemia (6%), increased lipase (6%), hyperkalemia (3%), and
increased aspartate aminotransferase (3%).
Please see full US Prescribing
Information and Medication Guide available
at www.BAVENCIO.com.
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
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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
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Consistent with our responsibility as one of the world's premier
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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 the EU as a monotherapy
for the treatment of adult patients with metastatic Merkel cell
carcinoma the alliance between Merck KGaA, Darmstadt, Germany, and Pfizer 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.
References
- BAVENCIO® (avelumab) EU SmPC. Available
at: http://www.ema.europa.eu/ema/
- 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.
- Stokes JB et al. Patients with Merkel cell carcinoma tumors
< or = 1.0 cm in diameter are unlikely to harbor
regional lymph node metastasis. Journal of Clinical Oncology
2009;27(23):3772-7.
- Allen PJ et al. Merkel cell carcinoma: prognosis and treatment
of Patients from a single institution. Journal of Clinical Oncology
2005;23(10):2300-9.
- IMMOMEC (European Commission). Merkel Cell Carcinoma. Available
from: http://www.immomec.eu/project/objectives/background/merkel-cell-carcinoma.
Last accessed August 2017.
- 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.
- 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 August 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.
Accessed September 2017.
- NCCN Merkel Cell Carcinoma Guidelines version I.
2017. www.nccn.org/professionals/physician_gls/PDF/mcc.pdf.
Last accessed June 2017.
- BAVENCIO Prescribing Information. 2017. Rockland, MA: EMD Serono Inc.
Contacts:
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