THOUSAND OAKS, Calif.,
Dec. 18, 2015 /PRNewswire/
-- Amgen (NASDAQ:AMGN) today announced that the European
Commission has approved the use of IMLYGIC™
(talimogene laherparepvec) for the treatment of adults with
unresectable melanoma that is regionally or distantly metastatic
(Stage IIIB, IIIC and IVM1a), with no bone, brain, lung or other
visceral disease. IMLYGIC is the first oncolytic immunotherapy to
demonstrate therapeutic benefit for patients with metastatic
melanoma in a Phase 3 clinical trial.
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IMLYGIC is derived from the herpes simplex type 1 virus (HSV-1)
, commonly called the cold sore virus. IMLYGIC has been modified to
replicate within tumors and to produce the immune stimulatory
protein human granulocyte-macrophage colony-stimulating factor
(GM-CSF). Administered via intralesional injection, IMLYGIC is
designed to cause the death of tumor cells and initiate an
anti-tumor immune response.
"As the first oncolytic immunotherapy authorized in the European
Union, the approval of IMLYGIC is an important milestone for this
new class of drugs, bringing patients with a rare and deadly form
of skin cancer a much needed new treatment option," said
Sean E. Harper, M.D., executive vice
president of Research and Development at Amgen. "By igniting
the body's own immune system IMLYGIC can initiate an anti-tumor
immune response, providing meaningful and durable response rates in
the early stage metastatic melanoma patient."
Melanoma remains a significant public health concern in the
European Union (EU), with an estimated 22,000 deaths from the
disease in 2012.1,2 While melanoma is curable when
detected in the early stages, metastatic melanoma continues to be
one of the most difficult-to-treat cancers because it is highly
aggressive and complex.3 Even with recent new options in
immune-oncology, a large number of patients with metastatic
melanoma still do not respond to treatment.4
The European approval included a review of exploratory subgroup
analyses of Study 005/05, referred to as OPTiM. The durable
response rate (DRR) in patients with Stage IIIB, IIIC and IVM1a
disease was 25.2 percent compared to 1.2 percent in those treated
with GM-CSF. In the study, patients with Stage IIIB, IIIC and IVM1a
disease achieved an overall response rate (ORR) of 40.5 percent
when treated with IMLYGIC compared to 2.3 percent with GM-CSF. The
median overall survival (OS) for IMLYGIC patients with Stage IIIB,
IIIC and IVM1a disease was 41.1 months compared to 21.5 months for
patients treated with GM-CSF. While the pivotal study was not
powered to evaluate efficacy in these individual subgroups,
patients with no visceral disease derived greater benefit from
IMLYGIC treatment than those with more advanced disease. Due to the
exploratory nature of the analysis and based on the current
evidence, it has not been established that IMLYGIC is associated
with an effect on OS.
The most commonly reported treatment-related adverse events were
fatigue, chills, pyrexia, nausea, influenza-like illness and
injection-site pain. Overall, 98 percent of these adverse reactions
reported were mild or moderate in severity. The most common grade 3
or higher adverse reaction was cellulitis. No fatal
treatment-related adverse events occurred.5
This approval grants a centralized marketing authorization in
the 28 countries that are members of the EU. Norway, Iceland and Liechtenstein, as members of the European
Economic Area (EEA), will take corresponding decisions on the basis
of the decision of the EC.
About the OPTiM Study
OPTiM was a global, randomized,
open-label Phase 3 trial evaluating the safety and efficacy of
IMLYGIC in patients with Stage IIIB, IIIC or IV melanoma when
resection was not recommended compared to GM-CSF. In the
436-patient study, IMLYGIC significantly improved DRR, the primary
endpoint of the trial, in the intent-to-treat population. DRR is
defined as the percent of patients with complete response (CR) or
partial response (PR) maintained continuously for a minimum of six
months. In the study, 16.3 percent of patients treated with IMLYGIC
achieved a DRR compared to 2.1 percent of patients treated with
GM-CSF (p<0.0001) in the intent-to-treat population. Of
the patients who experienced a durable response, 29.1 percent had a
durable CR and 70.8 percent had a durable PR. In the study, the
median time to response was 4.1 months (range: 1.2 to 16.7) in the
IMLYGIC arm.
A key secondary endpoint was OS. In the intent-to-treat
population, the median OS was 23.3 months in the group treated with
IMLYGIC compared to 18.9 months for those treated with GM-CSF
(p=0.0511). These results were not statistically
significant. The ORR for patients in the intent-to-treat population
was 26.4 percent for those treated with IMLYGIC compared to 5.7
percent in the GM-CSF arm. In an analysis to evaluate the systemic
activity of IMLYGIC, 34 percent of patients in the intent-to-treat
population had an overall decrease of at least 50 percent in
non-visceral lesions that were not injected.
About IMLYGICTM (talimogene laherparepvec) in
the EU
IMLYGIC is an oncolytic immunotherapy that is derived from HSV-1,
which is commonly called the cold sore virus. IMLYGIC has been
modified to replicate within tumors and to produce the immune
stimulatory protein human GM-CSF. IMLYGIC causes the death of tumor
cells and the release of tumor-derived antigens. It is thought
that, together with GM-CSF, it will promote a systemic anti-tumor
immune response and an effector T cell response.
Important EU Product Safety Information
This product is subject to additional monitoring. All
suspected adverse reactions should be reported in accordance with
the national reporting system.
The safety of IMLYGIC was evaluated in the pivotal study where
292 patients received at least one dose of IMLYGIC (see section
5.1). The median duration of exposure to IMLYGIC was 23 weeks (5.3
months). Twenty six (26) patients were exposed to IMLYGIC for at
least one year.
The most commonly reported adverse reactions (≥ 25 percent) in
IMLYGIC-treated patients were fatigue (50.3 percent), chills (48.6
percent), pyrexia (42.8 percent), nausea (35.6 percent),
influenza-like illness (30.5 percent), and injection site pain
(27.7 percent). Overall, ninety eight percent (98 percent) of these
adverse reactions reported were mild or moderate in severity. The
most common grade 3 or higher adverse reaction was cellulitis (2.1
percent) (see section 4.4).
Please refer to the Summary of Product Characteristics for
full European prescribing information.
About IMLYGIC™ (talimogene laherparepvec) in the
U.S.
In the U.S., IMLYGIC is indicated for the local
treatment of unresectable cutaneous, subcutaneous, and nodal
lesions in patients with melanoma recurrent after initial surgery.
IMLYGIC has not been shown to improve overall survival or have an
effect on visceral metastases.
Important U.S. Safety
Information
Contraindications
- Do not administer IMLYGIC™ to immunocompromised patients,
including those with a history of primary or acquired
immunodeficient states, leukemia, lymphoma, AIDS or other clinical
manifestations of infection with human immunodeficiency viruses,
and those on immunosuppressive therapy, due to the risk of
life-threatening disseminated herpetic infection.
- Do not administer IMLYGIC™ to pregnant patients.
Warnings and Precautions
- Accidental exposure to IMLYGIC™ may lead to
transmission of IMLYGIC™ and herpetic infection, including
during preparation and administration. Health care providers, close
contacts, pregnant women, and newborns should avoid direct contact
with injected lesions, dressings, or body fluids of treated
patients. The affected area in exposed individuals should be
cleaned thoroughly with soap and water and/or a disinfectant.
- Caregivers should wear protective gloves when assisting
patients in applying or changing occlusive dressings and observe
safety precautions for disposal of used dressings, gloves, and
cleaning materials. Exposed individuals should clean the affected
area thoroughly with soap and water and/or a disinfectant.
- To prevent possible inadvertent transfer of IMLYGIC™ to
other areas of the body, patients should be advised to avoid
touching or scratching injection sites or occlusive dressings.
- Herpetic infections: Herpetic infections (including
cold sores and herpetic keratitis) have been reported in IMLYGIC™
treated patients. Disseminated herpetic infection may also occur in
immunocompromised patients. Patients who develop suspicious
herpes-like lesions should follow standard hygienic practices to
prevent viral transmission.
- Patients or close contacts with suspected signs or symptoms of
a herpetic infection should contact their health care provider to
evaluate the lesions. Suspected herpetic lesions should be reported
to Amgen at 1-855-IMLYGIC (1-855-465-9442). Patients or
close contacts have the option of follow-up testing for further
characterization of the infection.
- IMLYGIC™ is sensitive to acyclovir. Acyclovir or other
antiviral agents may interfere with the effectiveness of IMLYGIC™.
Consider the risks and benefits of IMLYGIC™ treatment before
administering antiviral agents to manage herpetic infection.
- Injection Site Complications: Necrosis or
ulceration of tumor tissue may occur during
IMLYGIC™ treatment. Cellulitis and systemic bacterial
infection have been reported in clinical studies. Careful wound
care and infection precautions are recommended, particularly if
tissue necrosis results in open wounds.
- Impaired healing at the injection site has been reported.
IMLYGIC™ may increase the risk of impaired healing in patients
with underlying risk factors (e.g., previous radiation at the
injection site or lesions in poorly vascularized areas). If there
is persistent infection or delayed healing of the injection site,
consider the risks and benefits of continuing treatment.
- Immune-Mediated events including
glomerulonephritis, vasculitis, pneumonitis, worsening psoriasis,
and vitiligo have been reported in patients treated with IMLYGIC™.
Consider the risks and benefits of IMLYGIC™ before initiating
treatment in patients who have underlying autoimmune disease or
before continuing treatment in patients who develop immune-mediated
events.
- Plasmacytoma at Injection Site: Plasmacytoma in
proximity to the injection site has been reported in a patient with
smoldering multiple myeloma after IMLYGIC™ administration in a
clinical study. Consider the risks and benefits of IMLYGIC™ in
patients with multiple myeloma or in whom plasmacytoma develops
during treatment.
Adverse Reactions
- The most commonly reported adverse drug reactions (≥ 25
percent) in IMLYGIC™-treated patients were fatigue, chills,
pyrexia, nausea, influenza-like illness, and injection site pain.
Pyrexia, chills, and influenza-like illness can occur at any time
during IMLYGIC™ treatment, but were more frequent during the
first 3 months of treatment.
- The most common Grade 3 or higher adverse reaction was
cellulitis.
Please see full U.S. Prescribing Information, including
Medication Guide, for IMLYGIC at www.Amgen.com and
www.IMLYGIC.com.
About Amgen's Immuno-Oncology Focused
Partnerships
Amgen has in place a comprehensive clinical
development program investigating oncolytic immunotherapies for
their potential in melanoma and in a variety of other cancers.
Amgen's recent immuno-oncology focused partnerships include:
- A collaboration with Merck on developing IMLYGIC (talimogene
laherparepvec) and KEYTRUDA® (pembrolizumab) Merck's
anti-PD-1 therapy, in melanoma and squamous cell cancer of the head
and neck.
- A collaboration with Roche on a Phase 1b study to evaluate the
safety and efficacy of IMLYGIC in combination with Roche's
investigational anti-PDL1 therapy, atezolizumab (also known as
MPDL3280A), in patients with triple-negative breast cancer and
colorectal cancer with liver metastases.
- A strategic research collaboration and license agreement to
develop and commercialise the next generation of novel Chimeric
Antigen Receptor (CAR) T-cell immunotherapies with Kite
Pharma.
- A research collaborative agreement focusing on Amgen's
bispecific T-cell engager (BiTE®) antibody constructs
with MD Anderson's Moon Shots Program.
- A research and license agreement with Xencor to develop and
commercialise novel therapeutics in the areas of cancer
immunotherapy and inflammation. The research collaboration brings
together Amgen's capabilities in target discovery and protein
therapeutics with Xencor's XmAb® bispecific technology
platform.
About Amgen
Amgen is committed to unlocking
the potential of biology for patients suffering from serious
illnesses by discovering, developing, manufacturing and delivering
innovative human therapeutics. This approach begins by using tools
like advanced human genetics to unravel the complexities of disease
and understand the fundamentals of human biology.
Amgen focuses on areas of high unmet medical need and
leverages its biologics manufacturing expertise to strive for
solutions that improve health outcomes and dramatically improve
people's lives. A biotechnology pioneer since
1980, Amgen has grown to be one of the world's leading
independent biotechnology companies, has reached millions of
patients around the world and is developing a pipeline of medicines
with breakaway potential.
For more information, visit www.amgen.com and follow
us on www.twitter.com/amgen.
About Amgen's Commitment to Oncology
Amgen Oncology is
committed to helping patients take on some of the toughest cancers,
such as those that have been resistant to drugs, those that
progress rapidly through the body and those where limited treatment
options exist. Amgen's supportive care treatments help patients
combat certain side effects of strong chemotherapy, and our
targeted medicines and immunotherapies focus on more than a dozen
different malignances, ranging from blood cancers to solid tumors.
With decades of experience providing treatments for cancer
patients, Amgen continues to grow its portfolio of innovative and
biosimilar oncology medicines.
Forward-Looking Statements
This news release contains
forward-looking statements that are based on the current
expectations and beliefs of Amgen Inc. and its subsidiaries (Amgen
or us) and are subject to a number of risks, uncertainties and
assumptions that could cause actual results to differ materially
from those described. All statements, other than statements of
historical fact, are statements that could be deemed
forward-looking statements, including estimates of revenues,
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metrics, expected legal, arbitration, political, regulatory or
clinical results or practices, customer and prescriber patterns or
practices, reimbursement activities and outcomes and other such
estimates and results. Forward-looking statements involve
significant risks and uncertainties, including those discussed
below and more fully described in the Securities and Exchange
Commission (SEC) reports filed by Amgen Inc., including Amgen
Inc.'s most recent annual report on Form 10-K and any subsequent
periodic reports on Form 10-Q and Form 8-K. Please refer to Amgen
Inc.'s most recent Forms 10-K, 10-Q and 8-K for additional
information on the uncertainties and risk factors related to our
business. Unless otherwise noted, Amgen is providing this
information as of Dec. 17, 2015, and
expressly disclaims any duty to update information contained in
this news release.
No forward-looking statement can be guaranteed and actual
results may differ materially from those we project. Discovery or
identification of new product candidates or development of new
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guarantee that any particular product candidate or development of a
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References:
1. Boyle P, Doré JF, Autier P, et al. Cancer of the skin:
a forgotten problem in Europe.
Ann Oncol. 2004;15(1):5-6.
2. Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, et al.
Cancer incidence and mortality patterns in Europe: Estimates for 40 countries in 2012.
Eur J Cancer. 2013;49(6):1374-403.
3. American Cancer Society. Melanoma Skin Cancer. Available at:
http://www.cancer.org/acs/groups/cid/documents/webcontent/003120-pdf.pdf.
Accessed November 23, 2015.
4. Garbe C, Peris K, Hauschild A, et al. Diagnosis and treatment
of melanoma. European consensus-based interdisciplinary guideline –
Update 2012. Eur J Cancer. 2012;48:2375-90.
5. Andtbacka RHI, Kaufman HL, Collichio F, et al. Talimogene
Laherparepvec Improves Durable Response Rate in Patients With
Advanced Melanoma. J Clin Oncol. 2015;33(25):2780-8.
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