THOUSAND OAKS, Calif.,
Dec. 6, 2019 /PRNewswire/
-- Amgen (NASDAQ:AMGN) today announced that the U.S. Food and
Drug Administration (FDA) has approved AVSOLA™ (infliximab-axxq)
for all approved indications of the reference product,
Remicade® (infliximab): for the treatment of
moderate-to-severe rheumatoid arthritis (RA), moderate-to-severe
Crohn's Disease (CD) in the adult and pediatric population,
moderate-to-severe ulcerative colitis (UC) in the adult and
pediatric population, chronic severe plaque psoriasis (PsO),
psoriatic arthritis (PsA) and ankylosing spondylitis (AS).
"The approval of AVSOLA represents an important milestone
across our biosimilar and inflammation portfolios," said
Murdo Gordon, executive vice
president of Global Commercial Operations at Amgen. "Following
July's exciting launches of our two biosimilars in oncology,
AVSOLA highlights Amgen's long-term commitment to providing
more affordable biological treatment options to patients across
critical disease states, including chronic inflammatory
conditions."
AVSOLA, an anti-tumor necrosis factor alpha (anti-TNF)
monoclonal antibody, was proven to be highly similar to
Remicade with no clinically meaningful differences based on a
totality of evidence which included comparative analytical,
nonclinical and clinical data. The data package was composed of, in
part, results from a pharmacokinetic (PK) similarity study
conducted in healthy subjects, and a comparative clinical study
conducted in patients with moderate to severe RA.
The randomized, double-blind comparative clinical study
evaluated the efficacy and safety of AVSOLA compared to
Remicade in patients with moderate-to-severe RA. There were
558 patients enrolled and randomized (1:1) to receive either AVSOLA
or Remicade at a dose of 3 mg/kg administered as an infusion
on day 1, at weeks 2 and 6, and every 8 weeks thereafter. The
primary endpoint was the response difference (RD) of 20%
improvement in American College of Rheumatology core set
measurements (ACR20) at week 22. Key secondary endpoints included
DAS28-CRP change from baseline, RD of ACR20, ACR50 and ACR70 at
weeks 2, 6, 14, 22, 30, 34, 38, 46 and 50. The study
also incorporated the evaluation of a single transition in 119
subjects from Remicade to AVSOLA at week 22, which
demonstrated similar safety and immunogenicity in patients who were
previously on Remicade.
Amgen has a total of 10 biosimilars in its portfolio, four of
which have been approved in the U.S., and 3 that are approved in
the European Union (EU).
About AVSOLA™ (infliximab-axxq) in
the U.S.
AVSOLA is a biosimilar to Remicade, an anti-tumor
necrosis factor alpha (anti-TNF) monoclonal antibody. The active
ingredient of AVSOLA is an anti-TNF monoclonal antibody that
has the same amino acid sequence as Remicade. AVSOLA also has the
same pharmaceutical dosage form and strength as Remicade.
AVSOLA is currently not available commercially. This is
not an offer for sale. The following information is derived
from the approved label in the U.S.
In the U.S., AVSOLA is approved for:
Rheumatoid Arthritis
AVSOLA, 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.
Crohn's Disease
AVSOLA 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.
- reducing the number of draining enterocutaneous and
rectovaginal fistulas and maintaining fistula closure in adult
patients with fistulizing Crohn's disease.
Pediatric Crohn's Disease
AVSOLA 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 conventional therapy.
Ulcerative Colitis
AVSOLA 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.
Pediatric Ulcerative Colitis
AVSOLA 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 ulcerative colitis
who have had an inadequate response to conventional therapy.
Plaque Psoriasis
AVSOLA 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. AVSOLA should only be
administered to patients who will be closely monitored and have
regular follow-up visits with a physician.
Psoriatic Arthritis
AVSOLA 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.
Ankylosing Spondylitis
AVSOLA is indicated for reducing signs and symptoms in patients
with active ankylosing spondylitis.
AVSOLA™ U.S. Important Safety
Information
SERIOUS INFECTIONS
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 AVSOLA 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 AVSOLA use and during therapy. Treatment for latent
infection should be initiated prior to AVSOLA use.
- Invasive fungal infections, including histoplasmosis,
coccidioidomycosis, candidiasis, aspergillosis, blastomycosis,
pneumocystosis, and cryptococcosis. Patients may present with
disseminated, rather than localized, disease. Empiric antifungal
therapy should be considered in patients at risk for invasive
fungal infections who develop severe systemic illness.
- Bacterial, viral and other infections due to opportunistic
pathogens, including Legionella, Listeria and Salmonella.
The risks and benefits of treatment with AVSOLA™ should be
carefully considered prior to initiating therapy in patients with
chronic or recurrent infection. Patients should be closely
monitored for the development of signs and symptoms of infection
during and after treatment with AVSOLA™, 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 infection.
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 ulceration.
MALIGNANCIES
Lymphoma and other malignancies, some fatal, have been
reported in children and adolescent patients treated with tumor
necrosis factor (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 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 AVSOLA™, 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.
A population-based retrospective cohort study found a 2- to
3-fold increase in the incidence of invasive cervical cancer in
women with rheumatoid arthritis treated with infliximab compared to
biologics-naïve patients or the general population, particularly
those over 60 years of age. A causal relationship between
infliximab products and cervical cancer cannot be excluded.
Periodic screening should continue in women treated with
AVSOLA.
CONTRAINDICATIONS
AVSOLA 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. AVSOLA should be used with caution and
only after consideration of other treatment options. Patients
should be monitored closely. Discontinue AVSOLA if new or worsening
CHF symptoms appear. AVSOLA 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 product.
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 AVSOLA. For patients who
test positive, consult a physician with expertise in the treatment
of hepatitis B. Exercise caution when prescribing AVSOLA for
patients identified as carriers of HBV and monitor closely for
active HBV infection during and following termination of therapy
with AVSOLA. Discontinue AVSOLA in patients who develop HBV
reactivation and initiate antiviral therapy with appropriate
supportive treatment. Exercise caution when considering resumption
of TNF blocker‑ therapy and monitor patients closely.
HEPATOTOXICITY
Severe hepatic reactions, including acute liver failure,
jaundice, hepatitis and cholestasis, have been reported 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,
AVSOLA should be discontinued, and a thorough investigation of the
abnormality should be undertaken.
HEMATOLOGIC REACTIONS
Cases of leukopenia, neutropenia, thrombocytopenia, and
pancytopenia (some fatal) have been reported in patients receiving
infliximab products. The causal relationship to infliximab product
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 AVSOLA in patients who develop significant
hematologic abnormalities.
HYPERSENSITIVITY
Infliximab products have been associated with hypersensitivity
reactions that differ in their time of onset. Anaphylaxis,
urticaria, dyspnea, and hypotension have occurred in association
with infusions of infliximab products. Medications for the
treatment of hypersensitivity reactions should be available.
CARDIOVASCULAR AND CEREBROVASCULAR REACTIONS DURING AND AFTER
INFUSION
Serious cerebrovascular accidents, myocardial
ischemia/infarction (some fatal), hypotension, hypertension, and
arrhythmias have been reported during and within 24 hours of
initiation of infliximab product infusion. Cases of transient
visual loss have been reported during or within 2 hours of infusion
of infliximab. Monitor patients during infusion and if a serious
reaction occurs, discontinue infusion. Manage reactions according
to signs and symptoms.
NEUROLOGIC REACTIONS
Agents that inhibit TNF have been associated 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 AVSOLA in patients with these disorders and consider
discontinuation if these disorders develop.
AUTOIMMUNITY
Treatment with infliximab products may result in the formation
of autoantibodies and in the development of a lupus‑like syndrome.
Discontinue treatment with AVSOLA if symptoms of a lupus-like
syndrome develop.
ADVERSE REACTIONS
In clinical trials with infliximab products, the most common
adverse reactions occurring in >10% of patients included
infections (e.g., upper respiratory, sinusitis, and pharyngitis),
infusion-related reactions, headache, and abdominal pain.
USE WITH OTHER DRUGS
Concomitant use of AVSOLA with anakinra, abatacept, tocilizumab,
or other biologics used to treat the same conditions as AVSOLA 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 AVSOLA™ due to the possibility of clinical infections,
including disseminated infections.
Bring pediatric patients up to date with all vaccinations prior
to initiating AVSOLA™. 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.
Please see full Prescribing Information, including Boxed
WARNINGS, at www.Amgen.com.
About Amgen Biosimilars
Amgen is committed to
building upon Amgen's experience in the development and
manufacturing of innovative human therapeutics to
expand Amgen's reach to patients with serious illnesses.
Biosimilars will help to maintain Amgen's commitment to
connect patients with vital medicines, and Amgen is well
positioned to leverage its nearly four decades of experience in
biotechnology to create high-quality biosimilars and reliably
supply them to patients worldwide.
For more information,
visit www.amgenbiosimilars.com and follow us
on www.twitter.com/amgenbiosim.
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 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.
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CONTACT: Amgen, Thousand
Oaks
Kelley Davenport, 202-585-9637
(media)
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