New Indication for Amgen's Fifth FDA-approved
Biosimilar
Now Approved to Treat All Available
Rituxan® Indications
THOUSAND
OAKS, Calif., June 6, 2022
/PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced that the U.S.
Food and Drug Administration (FDA) has approved RIABNI™
(rituximab-arrx), a biosimilar to Rituxan®, in
combination with methotrexate for adults with moderate to severely
active rheumatoid arthritis (RA) who have had an inadequate
response to one or more tumor necrosis factor (TNF) antagonist
therapies. RIABNI is already approved for the treatment of adult
patients with Non-Hodgkin's Lymphoma (NHL), Chronic Lymphocytic
Leukemia (CLL), Granulomatosis with Polyangiitis (GPA) (also called
Wegener's Granulomatosis) and Microscopic Polyangiitis (MPA).
"The approval of RIABNI is an important advancement for
adults living with moderate to severe rheumatoid arthritis, a
chronic inflammatory joint disease, who now have access
to a proven and affordable
treatment option," said Murdo Gordon, executive vice
president of Global Commercial Operations at Amgen. "Our fully
integrated portfolio of innovative and biosimilar medicines for
inflammatory diseases reinforces our commitment to providing
patients with high-quality and affordable treatment options that
deliver substantial value to our healthcare system."
RIABNI, a CD20-directed cytolytic antibody, was proven to be
highly similar to, with no clinically meaningful differences in
safety or efficacy from, Rituxan (rituximab) based on totality of
evidence, which included comparative analytical, non-clinical and
clinical data.
The randomized, double-blind, comparative clinical study
compared the efficacy, safety, pharmacokinetics and immunogenicity
of RIABNI versus rituximab reference product (RP) in patients with
moderate to severe RA. Overall, 311 patients were randomized and
treated with RIABNI, rituximab RP approved in the EU (rituximab-EU)
or rituximab RP approved in the US (rituximab-US). The rituximab-US
group transitioned to RIABNI in period 2 of the study. The primary
efficacy endpoint, the change in disease activity score 28 using
C-reactive protein (DAS28-CRP) from baseline at week 24, was within
the predefined equivalence margin indicating equivalence in
clinical efficacy between RIABNI and rituximab RP. Safety,
pharmacokinetics and immunogenicity of RIABNI were similar to
rituximab RP.
Amgen has a total of 11 biosimilars in its portfolio including
potential treatments for chronic inflammatory diseases and cancer.
There are currently five biosimilars approved in the U.S. and three
approved in the European Union (EU) in Amgen's
portfolio.
About RIABNI™ (rituximab-arrx) in the U.S.
RIABNI is a biosimilar to Rituxan, an anti-CD20 monoclonal
antibody. The active ingredient of RIABNI is a monoclonal antibody
that has the same amino acid sequence as Rituxan. RIABNI also has
the same strength as Rituxan, and the dosage form and route of
administration are identical to Rituxan. RIABNI is not currently
indicated as a treatment for children with mature B-cell
Non-Hodgkin's lymphoma, mature B-cell acute leukemia, MPA, or GPA.
RIABNI is not indicated in adult patients with moderate to severe
pemphigus vulgaris (PV), for which Rituxan has orphan status.
In the U.S., RIABNI is approved for:
Non-Hodgkin's Lymphoma (NHL)
RIABNI (rituximab-arrx)
is indicated for the treatment of adult patients with:
- Relapsed or refractory, low-grade or follicular, CD20-positive,
B-cell NHL as a single agent.
- Previously untreated follicular, CD20-positive, B-cell NHL in
combination with first line chemotherapy and, in patients achieving
a complete or partial response to a rituximab product in
combination with chemotherapy, as single-agent maintenance
therapy.
- Non-progressing (including stable disease), low-grade,
CD20-positive, B-cell NHL as a single agent after first-line
cyclophosphamide, vincristine, and prednisone (CVP)
chemotherapy.
- Previously untreated diffuse large B-cell, CD20-positive NHL in
combination with cyclophosphamide, doxorubicin, vincristine,
prednisone (CHOP) or other anthracycline-based chemotherapy
regimens.
Chronic Lymphocytic Leukemia (CLL)
RIABNI, in
combination with fludarabine and cyclophosphamide (FC), is
indicated for the treatment of adult patients with previously
untreated and previously treated CD20-positive CLL.
Rheumatoid Arthritis (RA)
RIABNI, in combination with methotrexate, is indicated for the
treatment of adult patients with moderately- to severely- active
rheumatoid arthritis who have had an inadequate response to one or
more TNF antagonist therapies.
Granulomatosis with Polyangiitis (GPA) (Wegener's
Granulomatosis) and Microscopic
Polyangiitis (MPA)
RIABNI, in combination with
glucocorticoids, is indicated for the treatment of adult patients
with Granulomatosis with Polyangiitis (GPA) (Wegener's
Granulomatosis) and Microscopic Polyangiitis (MPA).
IMPORTANT SAFETY INFORMATION
BOXED WARNINGS: FATAL INFUSION-RELATED
REACTIONS, SEVERE MUCOCUTANEOUS REACTIONS, HEPATITIS B VIRUS
REACTIVATION, PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY
- Infusion-Related Reactions: Rituximab product administration
can result in serious, including fatal, infusion-related reactions.
Deaths within 24 hours of rituximab infusion have occurred.
Approximately 80% of fatal infusion-related reactions
occurred in association with the first infusion. Monitor
patients closely. Discontinue RIABNITM infusion
for severe reactions and provide medical treatment for Grade 3 or 4
infusion-related reactions.
- Severe Mucocutaneous Reactions: Severe, including fatal,
mucocutaneous reactions can occur in patients receiving rituximab
products. Discontinue RIABNITM in patients who
experience a severe mucocutaneous reaction. The safety of
readministration of RIABNITM to patients with severe
mucocutaneous reactions has not been determined.
- Hepatitis B Virus (HBV) Reactivation: HBV reactivation can
occur in patients treated with rituximab products, in some cases
resulting in fulminant hepatitis, hepatic failure, and death.
Screen all patients for HBV infection before treatment initiation,
and monitor patients during and after treatment with
RIABNITM. Discontinue RIABNITM and
concomitant medications in the event of HBV reactivation.
- Progressive Multifocal Leukoencephalopathy (PML), including
fatal PML, can occur in patients receiving rituximab
products. Discontinue RIABNITM and consider
discontinuation or reduction of any concomitant chemotherapy or
immunosuppressive therapy in patients who develop PML.
Warnings and Precautions
Infusion-Related Reactions (IRR)
- Rituximab products can cause severe, including fatal,
infusion-related reactions. Severe reactions typically occurred
during the first infusion with time to onset of 30-120
minutes.
- Rituximab product-induced infusion-related reactions and
sequelae include urticaria, hypotension, angioedema, hypoxia,
bronchospasm, pulmonary infiltrates, acute respiratory distress
syndrome, myocardial infarction, ventricular fibrillation,
cardiogenic shock, anaphylactoid events, or death.
- Premedicate patients with an antihistamine and acetaminophen
prior to dosing. For patients with Granulomatosis with Polyangiitis
(GPA) (Wegener's Granulomatosis) and Microscopic Polyangiitis
(MPA), methylprednisolone 100 mg intravenously or its equivalent is
recommended 30 minutes prior to each infusion. Institute
medical management (eg, glucocorticoids, epinephrine,
bronchodilators, or oxygen) for infusion-related reactions as
needed. Depending on the severity of the infusion-related reaction
and the required interventions, temporarily or permanently
discontinue RIABNI.TM Resume infusion at a minimum of
50% reduction in rate after symptoms have resolved.
- Closely monitor the following patients: those with pre-existing
cardiac or pulmonary conditions, those who experienced prior
cardiopulmonary adverse reactions, and those with high numbers of
circulating malignant cells (≥25,000/mm3).
Severe Mucocutaneous Reactions
- Mucocutaneous reactions, some with fatal outcome, can occur in
patients receiving rituximab products. These reactions include
paraneoplastic pemphigus, Stevens-Johnson syndrome, lichenoid
dermatitis, vesiculobullous dermatitis, and toxic epidermal
necrolysis.
- The onset of these reactions has been variable and includes
reports with onset on the first day of rituximab exposure.
Discontinue RIABNI in patients who experience a severe
mucocutaneous reaction. The safety of readministration of rituximab
products to patients with severe mucocutaneous reactions has not
been determined.
Hepatitis B Virus (HBV) Reactivation
- Hepatitis B virus (HBV) reactivation, in some cases resulting
in fulminant hepatitis, hepatic failure, and death, can occur in
patients treated with drugs classified as CD20-directed cytolytic
antibodies, including rituximab products. Cases have been reported
in patients who are hepatitis B surface antigen (HBsAg) positive
and also in patients who are HBsAg negative but are hepatitis B
core antibody (anti-HBc) positive. Reactivation also has occurred
in patients who appear to have resolved hepatitis B infection
(i.e., HBsAg negative, anti-HBc positive and hepatitis B surface
antibody [anti-HBs] positive).
- HBV reactivation is defined as an abrupt increase in HBV
replication manifesting as a rapid increase in serum HBV DNA level
or detection of HBsAg in a person who was previously HBsAg negative
and anti-HBc positive. Reactivation of HBV replication is often
followed by hepatitis, i.e., increase in transaminase levels. In
severe cases, increase in bilirubin levels, liver failure, and
death can occur.
- Screen all patients for HBV infection by measuring HBsAg and
anti-HBc before initiating treatment with RIABNI.TM For
patients who show evidence of prior hepatitis B infection (HBsAg
positive [regardless of antibody status] or HBsAg negative but
anti-HBc positive), consult with physicians with expertise in
managing hepatitis B regarding monitoring and consideration for HBV
antiviral therapy before and/or during RIABNI treatment.
- Monitor patients with evidence of current or prior HBV
infection for clinical and laboratory signs of hepatitis or HBV
reactivation during and for several months following
RIABNITM therapy. HBV reactivation has been reported up
to 24 months following completion of rituximab therapy.
- In patients who develop reactivation of HBV while on
RIABNITM, immediately discontinue RIABNITM
and any concomitant chemotherapy, and institute appropriate
treatment. Insufficient data exist regarding the safety of resuming
rituximab product treatment in patients who develop HBV
reactivation. Resumption of RIABNITM treatment in
patients whose HBV reactivation resolves should be discussed with
physicians with expertise in managing HBV.
Progressive Multifocal Leukoencephalopathy
(PML)
- JC virus infection resulting in multifocal leukoencephalopathy
(PML) and death can occur in rituximab product-treated patients
with hematologic malignancies or with autoimmune diseases. The
majority of patients with hematologic malignancies diagnosed with
PML received rituximab in combination with chemotherapy or as
part of a hematopoietic stem cell transplant. The patients with
autoimmune diseases had prior or concurrent immunosuppressive
therapy. Most cases of PML were diagnosed within 12 months of their
last infusion of rituximab.
- Consider the diagnosis of PML in any patient presenting with
new-onset neurologic manifestations. Evaluation of PML includes,
but is not limited to, consultation with a neurologist, brain MRI,
and lumbar puncture. Discontinue RIABNITM and consider
discontinuation or reduction of any concomitant chemotherapy or
immunosuppressive therapy in patients who develop PML.
Tumor Lysis Syndrome (TLS)
- Acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia,
or hyperphosphatemia from tumor lysis, sometimes fatal, can occur
within 12-24 hours after the first infusion of RIABNITM
in patients with non–Hodgkin's Lymphoma (NHL). A high number of
circulating malignant cells (≥25,000/mm3), or high tumor
burden, confers a greater risk of TLS.
- Administer aggressive intravenous hydration and
anti-hyperuricemic therapy in patients at high risk for TLS.
Correct electrolyte abnormalities, monitor renal function and fluid
balance, and administer supportive care, including dialysis, as
indicated.
Infections
- Serious, including fatal, bacterial, fungal, and new or
reactivated viral infections can occur during and following the
completion of rituximab product-based therapy. Infections have been
reported in some patients with prolonged hypogammaglobulinemia
(defined as hypogammaglobulinemia >11 months after rituximab
exposure).
- New or reactivated viral infections included cytomegalovirus,
herpes simplex virus, parvovirus B19, varicella zoster virus, West
Nile virus, and hepatitis B and C. Discontinue RIABNITM
for serious infections and institute appropriate anti-infective
therapy.
- RIABNITM is not recommended for use in patients with
severe, active infections.
Cardiovascular Adverse Reactions
- Cardiac adverse reactions, including ventricular fibrillation,
myocardial infarction, and cardiogenic shock may occur in patients
receiving rituximab products. Discontinue infusions for serious or
life-threatening cardiac arrhythmias. Perform cardiac monitoring
during and after all infusions of RIABNITM for patients
who develop clinically significant arrhythmias, or who have a
history of arrhythmia or angina.
Renal Toxicity
- Severe, including fatal, renal toxicity can occur after
rituximab product administration in patients with NHL. Renal
toxicity has occurred in patients who experience TLS and in
patients with NHL administered concomitant cisplatin therapy during
clinical trials. The combination of cisplatin and
RIABNITM is not an approved treatment regimen. Monitor
closely for signs of renal failure and discontinue
RIABNITM in patients with a rising serum creatinine or
oliguria.
Bowel Obstruction and Perforation
- Abdominal pain, bowel obstruction and perforation, in some
cases leading to death, can occur in patients receiving rituximab
products in combination with chemotherapy. In postmarketing
reports, the mean time to documented gastrointestinal perforation
was 6 (range 1−77) days in patients with NHL. Evaluate if
symptoms of obstruction such as abdominal pain or repeated vomiting
occur.
Immunization
- The safety of immunization with live viral vaccines
following rituximab product therapy has not been studied, and
vaccination with live virus vaccines is not recommended before or
during treatment.
- For patients treated with RIABNITM, physicians
should review the patient's vaccination status and patients should,
if possible, be brought up to date with all immunizations in
agreement with current immunization guidelines prior to initiating
RIABNI and administer non-live vaccines at least 4 weeks prior to a
course of RIABNI.TM
- The effect of rituximab products on immune responses was
assessed in a randomized, controlled study in patients with RA
treated with rituximab and methotrexate (MTX) compared to patients
treated with MTX alone.
- A response to pneumococcal vaccination (a T-cell independent
antigen) as measured by an increase in antibody titers to at least
6 of 12 serotypes was lower in patients treated with rituximab plus
MTX as compared to patients treated with MTX alone (19% vs 61%). A
lower proportion of patients in the rituximab plus MTX group
developed detectable levels of anti-keyhole limpet hemocyanin
antibodies (a novel protein antigen) after vaccination compared to
patients on MTX alone (47% vs 93%).
- A positive response to tetanus toxoid vaccine (a T-cell
dependent antigen with existing immunity) was similar in patients
treated with rituximab plus MTX compared to patients on MTX alone
(39% vs 42%). The proportion of patients maintaining a positive
Candida skin test (to evaluate delayed type hypersensitivity) was
also similar (77% of patients on rituximab plus MTX vs 70% of
patients on MTX alone).
- Most patients in the rituximab-treated group had B-cell counts
below the lower limit of normal at the time of immunization. The
clinical implications of these findings are not known.
Embryo-Fetal Toxicity
- Based on human data, rituximab products can cause fetal harm
due to B-cell lymphocytopenia in infants exposed in utero.
Advise pregnant women of the potential risk to a fetus.
Advise females of reproductive potential to use effective
contraception with RIABNITM and for 12 months after the
last dose.
Concomitant Use with Biologic Agents and DMARDs Other Than
MTX
- Limited data are available on the safety of the use of biologic
agents or DMARDs other than MTX in RA patients exhibiting
peripheral B-cell depletion following treatment with rituximab.
Observe patients closely for signs of infection if biologic agents
and/or DMARDs are used concomitantly. Use of concomitant
immunosuppressants other than corticosteroids has not been studied
in GPA, MPA, or PV patients exhibiting peripheral B-cell depletion
following treatment with rituximab products.
Use in Patients With RA Who Had No Prior Inadequate Response
to Tumor Necrosis Factor (TNF) Antagonists
- While the efficacy of rituximab was supported in 4 controlled
trials in patients with RA with prior inadequate responses to
nonbiologic DMARDs and in a controlled trial in MTX-naïve patients,
a favorable risk-benefit relationship has not been established in
these populations. The use of RIABNITM in patients with
RA who have not had prior inadequate response to one or more TNF
antagonists is not recommended.
Additional Important Safety Information
Adverse Reactions
Clinical Trials Experience in NHL and CLL
- The most common Grade 3 or 4 adverse reactions in clinical
trials of NHL and chronic lymphocytic leukemia (CLL) were
infusion-related reactions, neutropenia, leukopenia, anemia,
thrombocytopenia, and infections. Additionally, lymphopenia
and lung disorder were seen in NHL trials; and febrile neutropenia,
pancytopenia, hypotension, and hepatitis B were seen in CLL
trials.
- The most common adverse reactions (incidence ≥25%) in clinical
trials of NHL and CLL were infusion-related reactions.
Additionally, fever, lymphopenia, chills, infection, and asthenia
were seen in NHL trials; and neutropenia was seen in CLL
trials.
Clinical Trials Experience in RA
- Among all exposed patients, adverse reactions reported in
greater than 10% of patients include infusion-related reactions,
upper respiratory tract infection, nasopharyngitis, urinary tract
infection, and bronchitis.
- In placebo-controlled studies, adverse reactions reported in
≥5% of patients were hypertension (8% vs 5%), nausea (8% vs 5%),
upper respiratory tract infection (7% vs 6%), arthralgia (6% vs
4%), pyrexia (5% vs 2%), and pruritus (5% vs 1%) of
rituximab-treated vs placebo, respectively.
Infusion-Related Reactions
- In the rituximab RA pooled, placebo-controlled studies,
incidence of any adverse event within 24 hours of an infusion was
32% vs 23% after the first infusion, and 11% vs 13% after the
second infusion in the rituximab-treated patients and placebo
group, respectively. Incidence of acute infusion-related reactions
was 27% vs 19% after the first infusion, 9% vs 11% after the second
infusion in the rituximab-treated patients and placebo group,
respectively.
- Serious acute infusion-related reactions were experienced by
<1% of patients in either treatment group. Acute
infusion-related reactions required dose modification (stopping,
slowing, or interruption of the infusion) in 10% and 2% of patients
receiving rituximab or placebo, respectively, after the first
course.
Infections
- In the pooled, placebo controlled studies, incidence of
any type of infection was 39% vs 34%, rituximab-treated vs placebo.
The most common infections were nasopharyngitis, upper respiratory
tract infections, urinary tract infections, bronchitis, and
sinusitis. The incidence of serious infections was 2% vs 1%,
rituximab-treated vs placebo group.
- In the experience with rituximab in 2578 RA patients, the rate
of serious infection was 4.31 per 100 patient-years. The most
common serious infections (≥0.5%) were pneumonia or lower
respiratory tract infections, cellulitis, and urinary tract
infections. Fatal serious infections included pneumonia, sepsis,
and colitis. Rates of serious infection remain stable in patients
receiving subsequent courses.
- In 185 rituximab-treated RA patients with active disease,
subsequent treatment with a biologic DMARD, the majority of which
were TNF antagonists, did not appear to increase the rate of
serious infection.
Cardiovascular Adverse Reactions
- In the pooled, placebo-controlled studies, incidence of serious
cardiovascular reactions was 1.7% vs 1.3% rituximab-treated vs
placebo. Three cardiovascular deaths occurred during the
double-blind period of the RA studies including all rituximab
regimens (3/769=0.4%) compared to none in the placebo treatment
group (0/389).
- In the experience with rituximab in 2578 RA patients, the rate
of myocardial infarction (MI) was consistent with MI rates in the
general RA population. RIABNI should be discontinued in the event
of a serious or life-threatening cardiac event.
Hypophosphatemia and Hyperuricemia
- In the pooled, placebo-controlled studies, newly occurring
hypophosphatemia (<2.0 mg/dL) was 12% vs 10%, rituximab-treated
vs placebo, respectively. Hypophosphatemia was more common in
patients who received corticosteroids. Newly occurring
hyperuricemia (>10 mg/dL) was observed in 1.5% vs 0.3%,
rituximab-treated vs placebo, respectively.
Retreatment in Patients With RA
- In the experience with rituximab in RA patients, 2578 patients
have been exposed to rituximab and have received up to 10 courses
of rituximab in RA clinical trials, with 1890, 1043, and 425
patients having received at least 2, 3, and 4 courses,
respectively. Most of the patients who received additional courses
did so 24 weeks or more after the previous course and none were
retreated sooner than 16 weeks. The rates and types of adverse
reactions reported for subsequent courses of rituximab were similar
to rates and types seen for a single course of rituximab. In RA
Study 2, where all patients initially received rituximab, the
safety profile of patients who were retreated with rituximab was
similar to those who were retreated with placebo.
Immunogenicity
- A total of 273/2578 (11%) patients with RA tested positive for
anti-rituximab antibodies at any time after receiving rituximab.
Anti-rituximab antibody positivity was not associated with
increased infusion-related reactions or other adverse reactions.
Upon further treatment, the proportions of patients with
infusion-related reactions were similar between anti-rituximab
antibody positive and negative patients, and most reactions were
mild to moderate.
- Four anti-rituximab antibody positive patients had serious
infusion-related reactions, and the temporal relationship between
anti-rituximab antibody positivity and infusion-related reaction
was variable. The clinical relevance of anti-rituximab antibody
formation in rituximab-treated patients is unclear.
Clinical Trials Experience in GPA and MPA
- Adverse reactions reported in ≥15% of rituximab-treated
patients were infections, nausea, diarrhea, headache, muscle
spasms, anemia, peripheral edema, infusion-related reactions.
Induction Treatment of Patients with Active GPA/MPA (GPA/MPA
Study 1)
Infusion-Related Reactions
- In GPA/MPA Study 1, 12% vs 11% (rituximab-treated vs
cyclophosphamide) of patients experienced at least one
infusion-related reaction. Infusion-related reactions
included cytokine release syndrome, flushing, throat irritation,
and tremor. In the rituximab group, the proportion of patients
experiencing an infusion-related reaction was 12%, 5%, 4%, and 1%
following the first, second, third, and fourth infusions,
respectively. Patients were premedicated with antihistamine and
acetaminophen before each rituximab infusion and were on background
oral corticosteroids, which may have mitigated or masked an
infusion-related reaction; however, there is insufficient evidence
to determine whether premedication diminishes the frequency or
severity of infusion-related reactions.
Infections
- In GPA/MPA Study 1, 62% vs 47% (rituximab-treated vs
cyclophosphamide-treated, respectively) of patients experienced an
infection by Month 6. The most common infections in the rituximab
group were upper respiratory tract infections, urinary tract
infections, and herpes zoster. The incidence of serious infections
was 11% vs 10% (rituximab-treated vs cyclophosphamide,
respectively), with rates of approximately 25 and 28 per 100
patient-years, respectively. The most common serious infection was
pneumonia.
Hypogammaglobulinemia
- Hypogammaglobulinemia (IgA, IgG, or IgM below the lower limit
of normal) has been observed in patients with GPA and MPA treated
with rituximab in GPA/MPA Study 1. At 6 months, in the rituximab
group, 27%, 58%, and 51% of patients with normal immunoglobulin
levels at baseline had low IgA, IgG, and IgM levels, respectively
compared to 25%, 50%, and 46% in cyclophosphamide group.
Immunogenicity
- A total of 23/99 (23%) rituximab-treated patients with GPA or
MPA tested positive for anti-rituximab antibodies by 18 months in
GPA/MPA Study 1. The clinical relevance of anti-rituximab antibody
formation in rituximab-treated patients is unclear.
Treatment of Patients with GPA/MPA who have Achieved Disease
Control with Induction Treatment (GPA/MPA Study 2)
- In GPA/MPA Study 2, the safety profile was consistent with the
known safety profile of rituximab in immunologic indications.
Infusion-Related Reactions
- In GPA/MPA Study 2, 7/57 (12%) patients in the
non-U.S.-licensed rituximab arm reported infusion-related
reactions. The incidence of IRR symptoms was highest during or
after the first infusion (9%) and decreased with subsequent
infusions (<4%). One patient had two serious IRRs, two IRRs led
to a dose modification, and no IRRs were severe, fatal, or led to
withdrawal from the study.
Infections
- In GPA/MPA Study 2, 30/57 (53%) patients in the
non-U.S.-licensed rituximab arm and 33/58 (57%) in the azathioprine
arm reported infections. The incidence of all grade infections was
similar between the arms. The incidence of serious infections was
similar in both arms (12%). The most commonly reported serious
infection in the group was mild or moderate bronchitis.
Pregnancy and Nursing Mothers
- Based on human data, rituximab products can cause adverse
developmental outcomes including B-cell lymphocytopenia in infants
exposed in utero. Advise pregnant women of the risk to a
fetus. There are limited data on the presence of
rituximab products in human milk and the effect on the breastfed
child, and there are no data on the effect on milk
production. Rituximab is detected in the milk of lactating
cynomolgus monkeys, and maternal IgG is present in human breast
milk. Rituximab has also been reported to be excreted at low
concentrations in human breast milk. Given that the clinical
significance of this finding for children is not known, advise
women not to breastfeed during treatment with RIABNITM
and for 6 months after the last dose due to the potential for
serious adverse reactions in breastfed children.
Attention Healthcare Provider: Provide Medication Guide to
patient prior to RIABNITM infusion and advise patients
to read guide.
You may report side effects to the FDA at (800) FDA-1088
or www.fda.gov/medwatch. You may also report side effects to
Amgen at 1-800-772-6436.
Please see the full Prescribing Information,
including BOXED WARNINGS and Medication Guide, for additional
Important Safety Information.
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product marketing has in the past varied and we expect similar
variability in the future. Even when clinical trials are
successful, regulatory authorities may question the sufficiency for
approval of the trial endpoints we have selected. We develop
product candidates internally and through licensing collaborations,
partnerships and joint ventures. Product candidates that are
derived from relationships may be subject to disputes between the
parties or may prove to be not as effective or as safe as we may
have believed at the time of entering into such relationship. Also,
we or others could identify safety, side effects or manufacturing
problems with our products, including our devices, after they are
on the market.
Our results may be affected by our ability to successfully
market both new and existing products domestically and
internationally, clinical and regulatory developments involving
current and future products, sales growth of recently launched
products, competition from other products including biosimilars,
difficulties or delays in manufacturing our products and global
economic conditions. In addition, sales of our products are
affected by pricing pressure, political and public scrutiny and
reimbursement policies imposed by third-party payers, including
governments, private insurance plans and managed care providers and
may be affected by regulatory, clinical and guideline developments
and domestic and international trends toward managed care and
healthcare cost containment. Furthermore, our research, testing,
pricing, marketing and other operations are subject to extensive
regulation by domestic and foreign government regulatory
authorities. Our business may be impacted by government
investigations, litigation and product liability claims. In
addition, our business may be impacted by the adoption of new tax
legislation or exposure to additional tax liabilities. If we fail
to meet the compliance obligations in the corporate integrity
agreement between us and the U.S. government, we could become
subject to significant sanctions. Further, while we routinely
obtain patents for our products and technology, the protection
offered by our patents and patent applications may be challenged,
invalidated or circumvented by our competitors, or we may fail to
prevail in present and future intellectual property litigation. We
perform a substantial amount of our commercial manufacturing
activities at a few key facilities, including in Puerto Rico, and also depend on third parties
for a portion of our manufacturing activities, and limits on supply
may constrain sales of certain of our current products and product
candidate development. An outbreak of disease or similar public
health threat, such as COVID-19, and the public and governmental
effort to mitigate against the spread of such disease, could have a
significant adverse effect on the supply of materials for our
manufacturing activities, the distribution of our products, the
commercialization of our product candidates, and our clinical trial
operations, and any such events may have a material adverse effect
on our product development, product sales, business and results of
operations. We rely on collaborations with third parties for the
development of some of our product candidates and for the
commercialization and sales of some of our commercial products. In
addition, we compete with other companies with respect to many of
our marketed products as well as for the discovery and development
of new products. Further, some raw materials, medical devices and
component parts for our products are supplied by sole third-party
suppliers. Certain of our distributors, customers and payers have
substantial purchasing leverage in their dealings with us. The
discovery of significant problems with a product similar to one of
our products that implicate an entire class of products could have
a material adverse effect on sales of the affected products and on
our business and results of operations. Our efforts to collaborate
with or acquire other companies, products or technology, and to
integrate the operations of companies or to support the products or
technology we have acquired, may not be successful. A breakdown,
cyberattack or information security breach could compromise the
confidentiality, integrity and availability of our systems and our
data. Our stock price is volatile and may be affected by a number
of events. Our business and operations may be negatively affected
by the failure, or perceived failure, of achieving our
environmental, social and governance objectives. The effects of
global climate change and related natural disasters could
negatively affect our business and operations. Global economic
conditions may magnify certain risks that affect our business. Our
business performance could affect or limit the ability of our Board
of Directors to declare a dividend or our ability to pay a dividend
or repurchase our common stock. We may not be able to access the
capital and credit markets on terms that are favorable to us, or at
all.
CONTACT: Amgen, Thousand Oaks
Michael Strapazon, 805-313-5553
(media)
Jessica Akopyan, 805-447-0974
(media)
Arvind Sood, 805-447-1060
(investors)
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SOURCE Amgen