Merck Announces U.S. Launch of RENFLEXIS™ (infliximab-abda), a Biosimilar of Remicade, for All Eligible Indications
July 24, 2017 7:00 am ET
Merck (NYSE:MRK), known as MSD outside the United States and Canada,
today announced the U.S. launch of RENFLEXIS™ (infliximab-abda), a
biosimilar of the originator biologic medicine Remicade (infliximab).
RENFLEXIS was approved by the U.S. Food and Drug Administration (FDA) on
April 21 for all eligible indications. RENFLEXIS is the first medicine
available in the U.S. under a global biosimilars development and
commercialization agreement between Merck and Samsung Bioepis Co., Ltd.
“Merck looks forward to launching RENFLEXIS in the United States to help
meet the needs of patients, physicians and payers,” said Dora Bibila,
general manager, Merck Biosimilars. “As a global health care leader,
Merck believes that biosimilars have the potential to help increase
access to these important medicines while also providing savings for the
health care system.”
RENFLEXIS will be introduced in the U.S. at a list price (wholesaler
acquisition cost) of $753.39, representing a 35 percent discount to the
current list price of Remicade, its reference product. Wholesaler
acquisition costs do not include discounts that may be paid on the
Serious and sometimes fatal side effects have been reported with
infliximab products. Infections due to bacterial, mycobacterial,
invasive fungal, viral, or other opportunistic pathogens (e.g., TB,
histoplasmosis) have been reported. Lymphoma, including cases of fatal
hepatosplenic T-cell lymphoma (HSTCL), and other malignancies have been
reported, including in children and young adult patients. Due to the
risk of HSTCL, mostly reported in Crohn’s disease and ulcerative
colitis, assess the risk/benefit, especially if the patient is male and
is receiving azathioprine or 6-mercaptopurine treatment. RENFLEXIS is
contraindicated in patients with severe hypersensitivity reactions to
infliximab products and certain patients with congestive heart failure.
Other serious side effects reported include melanoma and Merkel cell
carcinoma, hepatitis B reactivation, hepatotoxicity, hematological
events, hypersensitivity, neurological events, and lupus-like syndrome.
Launch resources will include comprehensive education and support
services for health care professionals, patients and their caregivers,
including biosimilars education, disease education, and reimbursement
and access support.
The FDA approval of RENFLEXIS (infliximab-abda) was based on Samsung
Bioepis’ comprehensive data package, including analytical, nonclinical
and clinical pharmacokinetic, safety and effectiveness data
demonstrating that RENFLEXIS is highly similar to its reference product
Remicade, in terms of the safety, purity and potency of the product.
Indications for RENFLEXIS (infliximab-abda) for Injection, 100 mg
RENFLEXIS is a tumor necrosis factor (TNF) blocker approved in the U.S.
for the following indications.
Crohn’s Disease – RENFLEXIS is indicated for reducing signs and symptoms
and inducing and maintaining clinical remission in adult patients with
moderately to severely active Crohn’s disease who have had an inadequate
response to conventional therapy. RENFLEXIS is indicated for reducing
the number of draining enterocutaneous and rectovaginal fistulas and
maintaining fistula closure in adult patients with fistulizing Crohn’s
Pediatric Crohn’s Disease – RENFLEXIS is indicated for reducing signs
and symptoms and inducing and maintaining clinical remission in
pediatric patients 6 years of age and older with moderately to severely
active Crohn’s disease who have had an inadequate response to
Ulcerative Colitis – RENFLEXIS is indicated for reducing signs and
symptoms, inducing and maintaining clinical remission and mucosal
healing, and eliminating corticosteroid use in adult patients with
moderately to severely active ulcerative colitis who have had an
inadequate response to conventional therapy.
Rheumatoid Arthritis – RENFLEXIS, in combination with methotrexate, is
indicated for reducing signs and symptoms, inhibiting the progression of
structural damage, and improving physical function in patients with
moderately to severely active rheumatoid arthritis.
Ankylosing Spondylitis – RENFLEXIS is indicated for reducing signs and
symptoms in patients with active ankylosing spondylitis.
Psoriatic Arthritis – RENFLEXIS (infliximab-abda) is indicated for
reducing signs and symptoms of active arthritis, inhibiting the
progression of structural damage, and improving physical function in
patients with psoriatic arthritis.
Plaque Psoriasis – RENFLEXIS is indicated for the treatment of adult
patients with chronic severe (i.e., extensive and/or disabling) plaque
psoriasis who are candidates for systemic therapy and when other
systemic therapies are medically less appropriate. RENFLEXIS should only
be administered to patients who will be closely monitored and have
regular follow-up visits with a physician.
Selected Safety Information about RENFLEXIS (infliximab-abda)
Patients treated with infliximab products are at increased risk for
developing serious infections that may lead to hospitalization or death.
Most patients who developed these infections were taking concomitant
immunosuppressants such as methotrexate or corticosteroids. Discontinue
RENFLEXIS if a patient develops a serious infection or sepsis.
Reported infections include:
Active tuberculosis (TB), including reactivation of latent TB.
Patients frequently presented with disseminated or extrapulmonary
disease. Patients should be tested for latent TB before RENFLEXIS use
and during therapy.
Treatment for latent
infection should be initiated prior to RENFLEXIS use.
Invasive fungal infections, including histoplasmosis,
coccidioidomycosis, candidiasis, aspergillosis, blastomycosis and
pneumocystosis. Patients may present with disseminated, rather than
localized, disease. Empiric anti-fungal therapy should be considered
in patients at risk for invasive fungal infections who develop severe
Bacterial, viral, and other infections due to opportunistic
pathogens, including Legionella and Listeria.
The risks and benefits of treatment with RENFLEXIS should be carefully
considered prior to initiating therapy in patients with chronic or
recurrent infection. Closely monitor patients for the development of
signs and symptoms of infection during and after treatment with
RENFLEXIS, including the possible development of TB in patients who
tested negative for latent TB infection prior to initiating therapy, who
are on treatment for latent TB, or who were previously treated for TB
Risk of infection may be higher in patients greater than 65 years of
age, pediatric patients, patients with co-morbid conditions and/or
patients taking concomitant immunosuppressant therapy. In clinical
trials, other serious infections observed in patients treated with
infliximab products included pneumonia, cellulitis, abscess, and skin
Lymphoma and other malignancies, some fatal, have been reported in
children and adolescent patients treated with TNF blockers, including
infliximab products. Approximately half of these cases were
lymphomas, including Hodgkin’s and non-Hodgkin’s lymphoma. The other
cases represented a variety of malignancies, including rare malignancies
that are usually associated with immunosuppression and malignancies that
are not usually observed in children and adolescents. The malignancies
occurred after a median of 30 months after the first dose of therapy.
Most of the patients were receiving concomitant immunosuppressants.
Postmarketing cases of hepatosplenic T-cell lymphoma, a rare type of
T-cell lymphoma, have been reported in patients treated with TNF
blockers, including infliximab products. These cases have had a very
aggressive disease course and have been fatal. The majority of reported
cases have occurred in patients with Crohn’s disease or ulcerative
colitis and most were in adolescent and young adult males. Almost all of
these patients had received treatment with azathioprine or
6-mercaptopurine concomitantly with a TNF-blocker at or prior to
diagnosis. Carefully assess the risks and benefits of treatment with
RENFLEXIS (infliximab-abda), especially in these patient types.
In clinical trials of all TNF inhibitors, more cases of lymphoma were
observed compared with controls and the expected rate in the general
population. However, patients with Crohn’s disease, rheumatoid
arthritis, or plaque psoriasis may be at higher risk for developing
lymphoma. In clinical trials of some TNF inhibitors, including
infliximab products, more cases of other malignancies were observed
compared with controls. The rate of these malignancies among patients
treated with infliximab products was similar to that expected in the
general population, whereas the rate in control patients was lower than
expected. Cases of acute and chronic leukemia have been reported with
postmarketing TNF-blocker use. As the potential role of TNF inhibitors
in the development of malignancies is not known, caution should be
exercised when considering treatment of patients with a current or a
past history of malignancy or other risk factors such as chronic
obstructive pulmonary disease (COPD).
Melanoma and Merkel cell carcinoma have been reported in patients
treated with TNF-blocker therapy, including infliximab products.
Periodic skin examination is recommended for all patients, particularly
those with risk factors for skin cancer.
RENFLEXIS (infliximab-abda) is contraindicated in patients with moderate
to severe (NYHA Class III/IV) congestive heart failure (CHF) at doses
greater than 5 mg/kg. Higher mortality rates at the 10 mg/kg dose and
higher rates of cardiovascular events at the 5 mg/kg dose have been
observed in these patients. RENFLEXIS should be used with caution and
only after consideration of other treatment options. Patients should be
monitored closely. Discontinue RENFLEXIS if new or worsening CHF
symptoms appear. RENFLEXIS should not be (re)administered to patients
who have experienced a severe hypersensitivity reaction or to patients
with hypersensitivity to murine proteins or other components of the
HEPATITIS B REACTIVATION
TNF inhibitors, including infliximab products, have been associated with
reactivation of hepatitis B virus (HBV) in patients who are chronic
carriers. Some cases were fatal. Patients should be tested for HBV
infection before initiating RENFLEXIS. For patients who test positive,
consult a physician with expertise in the treatment of hepatitis B.
Exercise caution when prescribing RENFLEXIS for patients identified as
carriers of HBV and monitor closely for active HBV infection during and
following termination of therapy with RENFLEXIS. Discontinue RENFLEXIS
in patients who develop HBV reactivation and initiate antiviral therapy
with appropriate supportive treatment. Exercise caution when considering
resumption of RENFLEXIS and monitor patients closely.
Severe hepatic reactions, including acute liver failure, jaundice,
hepatitis, and cholestasis have been reported rarely in patients
receiving infliximab products postmarketing. Some cases were fatal or
required liver transplant. Aminotransferase elevations were not noted
prior to discovery of liver injury in many cases. Patients with symptoms
or signs of liver dysfunction should be evaluated for evidence of liver
injury. If jaundice and/or marked liver enzyme elevations (e.g., ≥5
times the upper limit of normal) develop, RENFLEXIS should be
discontinued, and a thorough investigation of the abnormality should be
Cases of leukopenia, neutropenia, thrombocytopenia, and pancytopenia
(some fatal) have been reported in patients using infliximab products.
The causal relationship to infliximab therapy remains unclear. Exercise
caution in patients who have ongoing or a history of significant
hematologic abnormalities. Advise patients to seek immediate medical
attention if they develop signs and symptoms of blood dyscrasias or
infection. Consider discontinuation of RENFLEXIS (infliximab-abda) in
patients who develop significant hematologic abnormalities.
Infliximab products have been associated with hypersensitivity reactions
that differ in their time of onset. Acute urticaria, dyspnea, and
hypotension have occurred in association with infusions of infliximab
products. Serious infusion reactions including anaphylaxis were
infrequent. Medications for the treatment of hypersensitivity reactions
should be available.
TNF inhibitors, including infliximab products, have been associated in
rare cases with CNS manifestation of systemic vasculitis, seizure, and
new onset or exacerbation of CNS demyelinating disorders, including
multiple sclerosis and optic neuritis, and peripheral demyelinating
disorders, including Guillain-Barré syndrome. Exercise caution when
considering RENFLEXIS in patients with these disorders and consider
discontinuation if these disorders develop.
Treatment with infliximab products may result in the formation of
autoantibodies and, rarely, in development of a lupus-like syndrome.
Discontinue treatment if symptoms of a lupus-like syndrome develop.
In clinical trials with infliximab products, the most common adverse
reactions occurring in >10% of patients treated with infliximab products
included, infections (e.g., upper respiratory, sinusitis, and
pharyngitis), infusion-related reactions, headache, and abdominal pain.
USE WITH OTHER DRUGS
Concomitant use of RENFLEXIS (infliximab-abda) with anakinra, abatacept,
tocilizumab or other biologics used to treat the same conditions as
RENFLEXIS is not recommended because of the possibility of an increased
risk of infection. Care should be taken when switching from one biologic
to another, since overlapping biological activity may further increase
the risk of infection.
LIVE VACCINES/THERAPEUTIC INFECTIOUS AGENTS
Live vaccines or therapeutic infectious agents should not be given with
RENFLEXIS due to the possibility of clinical infections, including
Bring pediatric patients up to date with all vaccinations prior to
initiating RENFLEXIS. At least a 6-month waiting period following birth
is recommended before the administration of any live vaccine to infants
exposed in utero to infliximab products.
About the Merck and Samsung Bioepis collaboration
Merck and Samsung Bioepis announced in February 2013 a development and
commercialization agreement under which Merck will commercialize
multiple biosimilar candidates in certain partnered territories. Under
terms of the agreement, Samsung Bioepis is responsible for preclinical
and clinical development, process development and manufacturing,
clinical trials and regulatory registration. Merck will be responsible
for all commercialization activities for products approved in its
For more than a century, Merck, a leading global biopharmaceutical
company known as MSD outside of the United States and Canada, has been
inventing for life, bringing forward medicines and vaccines for many of
the world’s most challenging diseases. Through our prescription
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work with customers and operate in more than 140 countries to deliver
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threaten people and communities around the world – including cancer,
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Please see Prescribing Information for RENFLEXIS (infliximab-abda),
including the Boxed Warning about serious infections and malignancies,
and Medication Guide for RENFLEXIS at
1. American Thoracic Society, Centers for Disease Control and
Prevention. Targeted tuberculin testing and treatment of latent
tuberculosis infection. Am J Respir Crit Care Med. 2000;161:S221-S247.
2. See latest Centers for Disease Control guidelines and recommendations
for tuberculosis testing in immunocompromised patients.
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