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Clinical endpoints: superior reductions vs Rebif in RMS over 2 years
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SUPERIOR RELAPSE RATE REDUCTIONS VS REBIF
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Annualized relapse rate with OCREVUS vs Rebif (interferon β-1a): OPERA I: 0.156 vs 0.292, OPERA II: 0.155 vs 0.290
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Relapses were defined as new
or worsening neurological symptoms that were attributable to multiple
sclerosis, persisted for over 24 hours, were immediately preceded by a
stable or improving neurological state for at least 30 days, and were
accompanied by objective neurological worsening as defined in the study
protocols.1
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SIGNIFICANT REDUCTION IN RISK OF 3‑MONTH CONFIRMED DISABILITY PROGRESSION VS REBIF
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Proportion of patients with confirmed disability progression: 9.8% OCREVUS vs 15.2% Rebif
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Important Safety Information
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Contraindications
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OCREVUS is contraindicated in patients with
active hepatitis B virus infection and in patients with a history of
life-threatening infusion reaction to OCREVUS.
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MRI endpoints: Significant relative reductions vs Rebif in RMS over 2 years
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NEAR-COMPLETE SUPPRESSION OF T1 GD+ LESIONS VS REBIF*
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Mean number of T1 Gd+ lesions with OCREVUS vs Rebif: OPERA I: 0.016 vs 0.286, OPERA II: 0.021 vs 0.416
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SUPERIORITY ON T2 LESION ENDPOINT VS REBIF
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Mean number of new or enlarging T2 hyperintense lesions with OCREVUS vs Rebif: OPERA I: 0.323 vs 1.413, OPERA II: 0.325 vs 1.904
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*The precise mechanism by which OCREVUS exerts its therapeutic effects in MS is unknown.
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| OPERA I and II Study Design |
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OPERA I and II (RMS): Two randomized,
double-blind, double-dummy, active comparator-controlled clinical trials
of identical design vs Rebif in 1656 patients (OCREVUS: OPERA I
[n=410], OPERA II [n=417]; Rebif: OPERA I [n=411], OPERA II [n=418])
with RMS treated for 96 weeks. Both studies included patients aged 18 to
55, who had experienced ≥ 1 relapse within the prior year, or ≥ 2
relapses within the prior 2 years, and had an EDSS score from 0 to 5.5.
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You can also learn more about OCREVUS for RMS at OCREVUS.com.
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| Infusion Reactions |
| OCREVUS
can cause infusion reactions, which can include pruritus, rash,
urticaria, erythema, bronchospasm, throat irritation, oropharyngeal
pain, dyspnea, pharyngeal or laryngeal edema, flushing, hypotension,
pyrexia, fatigue, headache, dizziness, nausea, and tachycardia. In
multiple sclerosis (MS) clinical trials, the incidence of infusion
reactions in OCREVUS-treated patients [who received methylprednisolone
(or an equivalent steroid) and possibly other pre-medication to reduce
the risk of infusion reactions prior to each infusion] was 34-40%, with
the highest incidence with the first infusion. There were no fatal
infusion reactions, but 0.3% of OCREVUS-treated MS patients experienced
infusion reactions that were serious, some requiring hospitalization. |
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Proven across clinical and MRI endpoints2
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CLINICAL ENDPOINTS
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3-month confirmed disability progression (primary endpoint)
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6-month confirmed disability progression
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Proportion of patients with 20% worsening of timed 25-foot walk
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MRI ENDPOINTS
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Percentage change in T2 lesion volume
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Percentage change in brain volume
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| ORATORIO Study Design |
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ORATORIO (PPMS): A randomized, double-blind,
placebo-controlled clinical trial in 732 patients (OCREVUS, n=488;
placebo, n=244) with PPMS treated for at least 120 weeks. Selection
criteria included patients aged 18 to 55 and required a baseline EDSS of
3 to 6.5 and a score of 2 or greater for the EDSS pyramidal FSS due to
lower extremity findings. Patients also had no history of RMS, SPMS, or
PRMS.
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EDSS=Expanded Disability Status Scale; Gd+=gadolinium-enhancing; FSS=functional systems score.
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You can also learn more about OCREVUS for PPMS at OCREVUS.com.
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OCREVUS is administered twice yearly as a 600 mg IV infusion†
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†The
first dose of OCREVUS is administered as two 300 mg IV infusions 2
weeks apart. Subsequent doses are administered as a single 600 mg
infusion every 6 months.
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References: 1. Hauser SL, Bar-Or A, Comi G, et al. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med. 2017;376(3):221-234. 2. Montalban X, Hauser SL, Kappos L, et al. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl J Med. 2017;376(3):209-220.
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Indication
|
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OCREVUS is indicated for the treatment of
adult patients with relapsing or primary progressive forms of multiple
sclerosis.
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Contraindications
|
|
OCREVUS is contraindicated in patients with
active hepatitis B virus infection and in patients with a history of
life-threatening infusion reaction to OCREVUS.
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Warnings and Precautions
|
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Infusion Reactions
|
|
OCREVUS can cause infusion reactions, which
can include pruritus, rash, urticaria, erythema, bronchospasm, throat
irritation, oropharyngeal pain, dyspnea, pharyngeal or laryngeal edema,
flushing, hypotension, pyrexia, fatigue, headache, dizziness, nausea,
and tachycardia. In multiple sclerosis (MS) clinical trials, the
incidence of infusion reactions in OCREVUS-treated patients [who
received methylprednisolone (or an equivalent steroid) and possibly
other pre-medication to reduce the risk of infusion reactions prior to
each infusion] was 34-40%, with the highest incidence with the first
infusion. There were no fatal infusion reactions, but 0.3% of
OCREVUS-treated MS patients experienced infusion reactions that were
serious, some requiring hospitalization.
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Observe patients treated with OCREVUS for
infusion reactions during the infusion and for at least one hour after
completion of the infusion. Inform patients that infusion reactions can
occur up to 24 hours after the infusion.
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Administer pre-medication (e.g.,
methylprednisolone or an equivalent corticosteroid, and an
antihistamine) to reduce the frequency and severity of infusion
reactions. The addition of an antipyretic (e.g., acetaminophen) may also
be considered. For life-threatening infusion reactions, immediately and
permanently stop OCREVUS and administer appropriate supportive
treatment. For less severe infusion reactions, management may involve
temporarily stopping the infusion, reducing the infusion rate, and/or
administering symptomatic treatment.
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Infections
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A higher proportion of OCREVUS-treated
patients experienced infections compared to patients taking REBIF or
placebo.
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Important Safety Information continued below.
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Warnings and Precautions (continued)
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A higher proportion of OCREVUS-treated
patients experienced infections compared to patients taking REBIF or
placebo. In RMS trials, 58% of OCREVUS-treated patients experienced one
or more infections compared to 52% of REBIF-treated patients. In the
PPMS trial, 70% of OCREVUS-treated patients experienced one or more
infections compared to 68% of patients on placebo. OCREVUS increased the
risk for upper respiratory tract infections, lower respiratory tract
infections, skin infections, and herpes-related infections. OCREVUS was
not associated with an increased risk of serious infections in MS
patients. Delay OCREVUS administration in patients with an active
infection until the infection is resolved.
|
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In RMS trials, 58% of OCREVUS-treated patients
experienced one or more infections compared to 52% of REBIF-treated
patients. In the PPMS trial, 70% of OCREVUS-treated patients experienced
one or more infections compared to 68% of patients on placebo. OCREVUS
increased the risk for upper respiratory tract infections, lower
respiratory tract infections, skin infections, and herpes-related
infections. OCREVUS was not associated with an increased risk of serious
infections in MS patients. Delay OCREVUS administration in patients
with an active infection until the infection is resolved.
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Respiratory Tract Infections
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|
A higher proportion of OCREVUS-treated patients
experienced respiratory tract infections compared to patients taking
REBIF or placebo. In RMS trials, 40% of OCREVUS-treated patients
experienced upper respiratory tract infections compared to 33% of
REBIF-treated patients, and 8% of OCREVUS-treated patients experienced
lower respiratory tract infections compared to 5% of REBIF-treated
patients. In the PPMS trial, 49% of OCREVUS-treated patients experienced
upper respiratory tract infections compared to 43% of patients on
placebo and 10% of OCREVUS-treated patients experienced lower
respiratory tract infections compared to 9% of patients on placebo. The
infections were predominantly mild to moderate and consisted mostly of
upper respiratory tract infections and bronchitis.
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Herpes
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In active-controlled (RMS) clinical trials, herpes
infections were reported more frequently in OCREVUS-treated patients
than in REBIF-treated patients, including herpes zoster (2.1% vs. 1.0%),
herpes simplex (0.7% vs. 0.1%), oral herpes (3.0% vs. 2.2%), genital
herpes (0.1% vs. 0%), and herpes virus infection (0.1% vs. 0%).
Infections were predominantly mild to moderate in severity. There were
no reports of disseminated herpes.
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In the placebo-controlled (PPMS) clinical trial,
oral herpes was reported more frequently in the OCREVUS-treated patients
than in the patients on placebo (2.7% vs 0.8%).
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Progressive Multifocal Leukoencephalopathy (PML)
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PML is an opportunistic viral infection of the
brain caused by the John Cunningham (JC) virus that typically only
occurs in patients who are immunocompromised, and that usually leads to
death or severe disability. Although no cases of PML were identified in
OCREVUS clinical trials, JC virus infection resulting in PML has been
observed in patients treated with other anti-CD20 antibodies and other
MS therapies and has been associated with some risk factors (e.g.,
immunocompromised patients, polytherapy with immunosuppressants). At the
first sign or symptom suggestive of PML, withhold OCREVUS and perform
an appropriate diagnostic evaluation. MRI findings may be apparent
before clinical signs or symptoms. Typical symptoms associated with PML
are diverse, progress over days to weeks, and include progressive
weakness on one side of the body or clumsiness of limbs, disturbance of
vision, and changes in thinking, memory, and orientation leading to
confusion and personality changes. (per USPI)
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Hepatitis B Virus (HBV) Reactivation
|
|
There were no reports of hepatitis B reactivation
in MS patients treated with OCREVUS. Fulminant hepatitis, hepatic
failure, and death caused by HBV reactivation have occurred in patients
treated with other anti-CD20 antibodies. Perform HBV screening in all
patients before initiation of treatment with OCREVUS. Do not administer
OCREVUS to patients with active HBV confirmed by positive results for
HBsAg and anti-HB tests.
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For patients who are negative for surface antigen
[HBsAg] and positive for HB core antibody [HBcAb+] or are carriers of
HBV [HBsAg+], consult liver disease experts before starting and during
treatment.
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Possible Increased Risk of Immunosuppressant Effects with Other Immunosuppressants
|
|
When initiating OCREVUS after an immunosuppressive
therapy or initiating an immunosuppressive therapy after OCREVUS,
consider the potential for increased immunosuppressive effect. OCREVUS
has not been studied in combination with other MS therapies.
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Vaccinations
|
|
Administer all immunizations according to
immunization guidelines at least 6 weeks prior to initiation of OCREVUS.
|
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The safety of immunization with live or
live-attenuated vaccines following OCREVUS therapy has not been studied
and vaccination with live-attenuated or live vaccines is not recommended
during treatment and until B-cell repletion.
|
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No data are available on the effects of live or non-live vaccination in patients receiving OCREVUS.
|
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Malignancies
|
|
An increased risk of malignancy with OCREVUS may
exist. In controlled trials, malignancies, including breast cancer,
occurred more frequently in OCREVUS-treated patients. Breast cancer
occurred in 6 of 781 females treated with OCREVUS and none of 668
females treated with REBIF or placebo. Patients should follow standard
breast cancer screening guidelines.
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Use in Specific Populations
|
|
Pregnancy
|
|
There are no adequate data on the developmental
risk associated with use of OCREVUS in pregnant women. There are no data
on B-cell levels in human neonates following maternal exposure to
OCREVUS. However, transient peripheral B-cell depletion and
lymphocytopenia have been reported in infants born to mothers exposed to
other anti-CD20 antibodies during pregnancy. OCREVUS is a humanized
monoclonal antibody of an immunoglobulin G1 subtype and immunoglobulins
are known to cross the placental barrier.
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Lactation
|
|
There are no data on the presence of ocrelizumab
in human milk, the effects on the breastfed infant, or the effects of
the drug on milk production. Ocrelizumab was excreted in the milk of
ocrelizumab-treated monkeys. Human IgG is excreted in human milk, and
the potential for absorption of ocrelizumab to lead to B-cell depletion
in the infant is unknown. The developmental and health benefits of
breastfeeding should be considered along with the mother’s clinical need
for OCREVUS and any potential adverse effects on the breastfed infant
from OCREVUS or from the underlying maternal condition.
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Females and Males of Reproductive Potential
|
|
Women of childbearing potential should use
contraception while receiving OCREVUS and for 6 months after the last
infusion of OCREVUS.
|
|
Most Common Adverse Reactions
|
|
RMS: The most common adverse
reactions in RMS trials (incidence ≥10% and >REBIF) were upper
respiratory tract infections (40%) and infusion reactions (34%).
|
|
PPMS: The most common adverse
reactions in PPMS trials (incidence ≥10% and >placebo) were upper
respiratory tract infections (49%), infusion reactions (40%), skin
infections (14%), and lower respiratory tract infections (10%).
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For additional safety information, please see the full Prescribing Information and Medication Guide.
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