For Patients and Caregivers

RMSRELAPSE RATE REDUCTIONS

Proven superior relapse reduction vs Rebif® (interferon beta-1a)1

OCREVUS reduced annualized relapse rates (ARR) by nearly half1

Controlled period primary endpoint1

OPERA I

46%

Relative reductions p<0.0001
ARR with OCREVUS vs Rebif:

0.156 vs 0.292

OPERA II

47%

Relative reductions p<0.0001
ARR with OCREVUS vs Rebif:

0.155 vs 0.290

ARR through 10+ years (controlled and open-label extension [OLE] periods)2
ARRs observed in the OLE period were consistent with the controlled period2

Relapses were defined as new or worsening neurologic 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. Measurements performed at intermediate timepoints were not prespecified in the statistical testing hierarchy and reflect numerical trends only.3

Limitations of the open-label, uncontrolled study period

Patients in the OLE period successfully completed the controlled period and are subject to continued dropout; they may represent an enriched population. The endpoints measured were not prespecified or powered to conclude statistical significance; they only convey numerical trends. Conclusions regarding the treatment effect of OCREVUS cannot be drawn on the basis of OLE data. Measurements performed at intermediate timepoints were not prespecified in the statistical testing hierarchy and reflect numerical trends only.

RMSIMPACT ON DISABILITY

Impact on disability across 3 endpoints at Year 2

OCREVUS reduced the risk of disability progression in 3 endpoints across 2 identical RMS trials1

Superior reduction in risk of confirmed disability progression (CDP) vs Rebif (controlled period)

12-week CDP (proportion of patients)1

40%

Risk reduction

HR (95% CI): 0.60 (0.45, 0.81)
p=0.0006

Prespecified, pooled analysis:
9.8% OCREVUS vs 15.2% Rebif

In the individual OPERA studies4:
OPERA I: 7.6% OCREVUS vs 12.2% Rebif
OPERA II: 10.6% OCREVUS vs 15.1% Rebif

24-week CDP (proportion of patients)4

40%

Risk reduction

HR (95% CI): 0.60 (0.43, 0.84)
p=0.003

Prespecified, pooled analysis:
7.6% OCREVUS vs 12% Rebif

In the individual OPERA studies4:
OPERA I: 5.9% OCREVUS vs 9.5% Rebif
OPERA II: 7.9% OCREVUS vs 11.5% Rebif

48-week CDP vs Rebif (controlled period, post hoc analysis)5,6

  • 57% risk reduction (proportion of patients: 3.2% OCREVUS vs 7.2% Rebif)
  • Not prespecified to conclude statistical significance; these data only convey numerical trends
  • 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 who had experienced ≥1 relapse within the prior year, or 2 relapses within the prior 2 years, and had an EDSS score between 0 and 5.5. The primary outcome of both studies was ARR4,7

Limitations

  • Patients in the OLE period successfully completed the controlled period and are subject to continued dropout; they may represent an enriched population. The endpoints measured were not prespecified or powered to conclude statistical significance; they only convey numerical trends. Conclusions regarding the treatment effect of OCREVUS cannot be drawn on the basis of OLE data

Disability data through 10+ years7

Time to onset of 24-week CDP (controlled and OLE periods)7,8

In the controlled period, fewer OCREVUS patients experienced disability progression than those who started on Rebif

Photo of a woman trying on a hat

>9 out of 10 patients treated with OCREVUS remained free from disability progression (12- and 24-week CDP)1,4

Significant difference in CDI vs Rebif (controlled period)4

>20% of OCREVUS-treated patients showed CDI

Confirmed disability progression (CDP) was defined as patients with EDSS score ≤5.5 who experienced an EDSS score increase of ≥1.0. For patients with EDSS score >5.5, progression was an EDSS score increase of ≥0.5. Disability progression was categorized as confirmed if it was present at 12 or 24 weeks over the treatment period.

Confirmed disability improvement (CDI) was defined as a reduction from the baseline EDSS score of at least 1.0 point (or 0.5 points if the baseline EDSS score was >5.5) that was sustained for at least 12 weeks in patients with a baseline EDSS score of at least 2.0.

Prespecified pooled analysis4
12-week CDI

(proportion of patients)

33%

DIFFERENCE
p=0.02

Pooled analysis:
20.7% OCREVUS vs 15.6% Rebif

PPMSIMPACT ON DISABILITY

OCREVUS significantly reduced the risk of disability progression vs placebo1*

Primary endpoint: 12-week CDP1
 

24%

Risk reduction1,9
HR (95% CI): 0.76 (0.59, 0.98) 

p=0.0321

20% worsening of timed 25-foot walk confirmed at 12 weeks1

25%

Risk reduction1

*Median treatment duration over 3 years.1

RMSNEDA BY WEEK 96

NEDA by Week 96 (post hoc analysis)

 

No evidence of disease activity (NEDA) in the controlled period, including re-baselined analysis

NEDA is the proportion of RMS patients with4:
  • No protocol-defined relapses
  • No 3-month or 6-month CDP
  • No T1 Gd+ MRI activity
  • No new or enlarging T2 lesions

Controlled period NEDA10
Pooled analysis

48%
OCREVUS
 vs 27%
Rebif

Weeks 0-96

  • The predefined secondary endpoint was not statistically significant, and it was considered nonconfirmatory because it fell below the break in the statistical hierarchy at change in Multiple Sclerosis Functional Composite Scale (MSFCS) score from baseline to Week 963,4
  • Exploratory result based on modified ITT population3,4

Re-baselined NEDA data (post hoc analysis)

Why re-baseline NEDA data?10

NEDA analyses are often re-baselined, or calculated at a later timepoint, in order to minimize any confounding impact of pretreatment disease activity and to better reflect the steady state of DMT impact on disability worsening and disease activity.

Re-baselined NEDA10
Pooled analysis

72%
OCREVUS
 vs 42%
Rebif

Weeks 24-96
(re-baselined to 24 weeks)

82%
OCREVUS
 vs 57%
Rebif

Weeks 48-96
(re-baselined to 48 weeks)

  • During Weeks 48 to 96, the lower frequency of MRI scans compared with other time periods may have influenced the proportion of patients maintaining NEDA10
  • Moving into the clinical practice setting, the optimal timing of re-baselining should reflect the anticipated timing for reaching full efficacy with DMT in order to give a more reliable indication of subsequent drug failure10
  • Conclusions from cross-trial comparisons are limited because of differences including comparators, patient populations, MRI techniques, frequency of assessments, analysis methods, and definitions of NEDA10

RMSLESION ACTIVITY

T1 Gd+ & T2 lesion activity

T1 Gd+ lesions in RMS trials T2 lesion activity in RMS

Superior reductions in mean number of T1 Gd+ lesions over 2 years1

Near-complete suppression of T1 Gd+ lesions*

94%

OPERA I

95%

OPERA II

Relative reductions
p<0.0001

OCREVUS vs Rebif:

OPERA I: 0.016 vs 0.286

OPERA II: 0.021 vs 0.416

T1 Gd+ lesions (controlled and OLE periods)7†

Conclusions regarding the treatment effect of OCREVUS (ocrelizumab) cannot be drawn on the basis of OLE data.1 *The precise mechanism by which OCREVUS exerts its therapeutic effects in MS is unknown.1
†Relative reductions vs Rebif in T1 Gd+ lesions were observed in the controlled period at each of the intermediate timepoints, Weeks 24, 48, and 96. The measurements performed at these intermediate timepoints were not prespecified in the statistical testing hierarchy and reflect numerical trends only.3,4 Unadjusted controlled and OLE data include the ITT population; clinical cutoff date: November 2022. Number of T1 Gd+ lesions at each timepoint for all patients in the treatment group divided by the total number of brain MRI scans at that timepoint.3,7

Superior reductions in mean number of T2 lesions over 2 years1

77%

OPERA I

83%

OPERA II

Relative reductions
p<0.0001

OCREVUS vs Rebif:

OPERA I: 0.323 vs 1.413

OPERA II: 0.325 vs 1.904

New or enlarging T2 lesions (controlled and OLE periods)7†

Conclusions regarding the treatment effect of OCREVUS (ocrelizumab) cannot be drawn on the basis of OLE data.1 †Relative reductions in T2 lesions were observed in the controlled period at each of the intermediate timepoints: Weeks 24, 48, and 96. The measurements performed at these intermediate timepoints were not prespecified in the statistical testing hierarchy and reflect numerical trends only.3 Unadjusted controlled and OLE data include the ITT population; clinical cutoff date: November 2022. Number of new or enlarging T2 lesions relative to preceding scan for all patients in the treatment group at each timepoint for all patients in the treatment group divided by the total number of brain MRI scans at that timepoint.3,7

PPMSLESION ACTIVITY

OCREVUS treatment resulted in a significant difference in mean change in T2 lesion volume vs placebo1

Mean change in volume of T2 lesions (CM)1

SIGNIFICANT
DIFFERENCE

p<0.0001

All endpoints were studied from baseline to Week 120. Neurological evaluations were performed every 12 weeks and at every infusion cycle. Brain MRIs were performed at baseline and at Weeks 24, 48, and 120.1

In exploratory subgroup analyses of ORATORIO, the proportion of female patients with disability progression confirmed at 12 weeks after onset was similar in patients treated with OCREVUS and placebo, respectively (approximately 36% in each group). In male patients, the proportion of patients with disability progression confirmed at 12 weeks after onset was approximately 30% in OCREVUS-treated patients and 43% in placebo-treated patients. Clinical and MRI endpoints that generally favored OCREVUS numerically in the overall population, and that showed similar trends in both male and female patients, included annualized relapse rate, change in T2 lesion volume, and number of new or enlarging T2 lesions. ORATORIO was not powered to detect differences in these subgroups.1,9

RMSSTUDY DESIGN

OPERA I/II were identical head-to-head RMS trials of OCREVUS vs Rebif® (interferon beta-1a)4

 

Select baseline characteristics of patients in OCREVUS trials for RMS

60%

of patients studied were younger than 40 years of age11

3/4

of all patients had no DMT within the previous 2 years1

45%

of all patients were diagnosed within
2 years of screening and were treatment naive12,13

37 years

was the mean age of patients with approximately 4 years from MS diagnosis to trial participation1

40%

of patients had an EDSS score of <2.51,11
Patients in the controlled period had to have an EDSS score between 0 and 5.5

40%

of patients had ≥1 T1 Gd+ lesions, thought to represent acute inflammation1,14

Icon of a group of people Average patient in the controlled period1,4 Age: 37 Mean EDSS score: 2.8 Mean number of T1 Gd+ lesions: 1.8 Mean number of T2 lesions: 51.0 Untreated within 2 years: 74% Mean time since diagnosis: 4 years

OPERA I and OPERA II pooled analysis4,7

  • Patients who received Rebif during the controlled period continued to receive Rebif during the open-label extension (OLE) screening period until their first infusion of OCREVUS7,15
  • In the OLE phase, the first 600-mg dose of OCREVUS was administered as two 300-mg infusions given 2 weeks apart7

Key inclusion criteria4

  • ≥2 relapses within the last 2 years
  • EDSS score from 0.0 to 5.5

Controlled and OLE study endpoints4,5

  • Annualized relapse rate (primary endpoint)
  • 12-week and 24-week confirmed disability progression (CDP) in the controlled period and 24-week and 48-week CDP in the OLE period
  • Confirmed disability improvement (CDI) at 12 weeks through 96 weeks
  • Mean number of T1 Gd+ lesions and new or enlarging T2 hyperintense lesions per MRI at Weeks 24, 48, and 96
  • Exploratory composite endpoint: proportion of patients with no evidence of disease activity (NEDA) in the controlled period
  • Safety

Patients in the OLE period successfully completed the controlled period and are subject to continued dropout; they may represent an enriched population. Measured endpoints only convey numerical trends and were not or powered to conclude statistical significance. Conclusions regarding the treatment effect of OCREVUS cannot be drawn on the basis of OLE data

PPMSSTUDY DESIGN

ORATORIO clinical trial for PPMS

>2-year clinical trial for the first and only FDA-approved PPMS therapy

Patients were randomized 2:1 and received either OCREVUS or placebo as two 300-mg IV infusions administered 2 weeks apart every 24 weeks throughout the treatment period.9

OCREVUS: n=4881

Placebo: n=2441

*2005 revised McDonald criteria.

ORATORIO patient demographics1,9

Photo of a hispanic woman lifting weights in a gym

Only aCD20 for MS with 10+ years of clinical trial experience7

*OCREVUS: OPERA I, n=410; OPERA II, n=417. Rebif: OPERA I, n=411; OPERA II, n=418.4
†OCREVUS arm: 600-mg intravenous (IV) dose every 24 weeks (first dose: two 300-mg IV infusions 2 weeks apart), or placebo as subcutaneous (SC) injections 3 times/week; Rebif arm: 44-μg SC 3 times/week or placebo IV infusions every 24 weeks.4 aCD20=anti-CD20; ARR=annualized relapse rate; CDI=confirmed disability improvement; CDP=confirmed disability progression; DMT=disease-modifying treatment; EDSS=Expanded Disability Status Scale; FDA=Food and Drug Administration; HR=hazard ratio; ITT=intent-to-treat; IV=intravenous; MRI=magnetic resonance imaging; MS=multiple sclerosis; NEDA=no evidence of disease activity; OLE=open-label extension; PPMS=primary progressive multiple sclerosis; RMS=relapsing multiple sclerosis; SC=subcutaneous; T1 Gd+=T1 gadolinium-enhancing; T2=transverse relaxation time.

NEXT: OCREVUS [IV] Safety

 

Important Safety Information & Indications

Indications

OCREVUS and OCREVUS ZUNOVO are indicated for the treatment of:

  • Relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults
  • Primary progressive MS, in adults.
Contraindications

Treatment with ocrelizumab is contraindicated in patients with active hepatitis B virus infection and in patients with a history of life-threatening administration reactions to ocrelizumab. OCREVUS ZUNOVO is also contraindicated in patients with a history of hypersensitivity to ocrelizumab, hyaluronidase, or any component of OCREVUS ZUNOVO.

Warnings and Precautions
Injection Reactions (OCREVUS ZUNOVO) OR Infusion Reactions (OCREVUS)

OCREVUS ZUNOVO can cause injection reactions, which can be local or systemic. Common symptoms of local injection reactions reported by patients treated with OCREVUS ZUNOVO in multiple sclerosis (MS) clinical trials included erythema, pain, swelling, and pruritus. Common symptoms of systemic injection reactions reported by patients included headache and nausea. In an open-label, active-controlled trial, injection reactions were more frequently reported with the first injection; 49% of patients experienced an injection reaction with the first injection.

In OCREVUS MS clinical trials, the incidence of infusion reactions in patients [who received methylprednisolone (or an equivalent steroid) and possibly other pre-medication to reduce the risk of infusion reactions prior to infusion] was 34% to 40%, with the highest incidence with the first infusion. There were no fatal infusion reactions, but 0.3% of intravenous ocrelizumab-treated MS patients experienced infusion reactions that were serious, some requiring hospitalization. Symptoms of infusion reactions can include pruritus, rash, urticaria, erythema, bronchospasm, throat irritation, oropharyngeal pain, dyspnea, pharyngeal or laryngeal edema, flushing, hypotension, pyrexia, fatigue, headache, dizziness, nausea, tachycardia, and anaphylaxis.

Monitor OCREVUS ZUNOVO patients during and after injections. 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 administration reactions can occur during or within 24 hours of treatment.

Reducing the Risk and Managing Injection or Infusion Reactions

For OCREVUS ZUNOVO, administer oral pre-medication (e.g., dexamethasone or an equivalent corticosteroid, and an antihistamine) at least 30 minutes prior to each OCREVUS ZUNOVO injection to reduce the risk of injection reactions. The addition of an antipyretic (e.g., acetaminophen) may also be considered.

For OCREVUS, 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.

Management recommendations depend on the type and severity of the reaction. For life-threatening reactions, immediately and permanently stop OCREVUS ZUNOVO or OCREVUS and administer appropriate supportive treatment. For less severe OCREVUS ZUNOVO injection reactions, the injection should be interrupted immediately, and the patient should receive symptomatic treatment. The injection should be completed at the healthcare provider’s discretion and only after all symptoms have resolved. For less severe OCREVUS infusion reactions, management may involve temporarily stopping the infusion, reducing the infusion rate, and/or administering symptomatic treatment.

Infections

Serious, including life-threatening or fatal, bacterial, viral, parasitic and fungal infections have been reported in patients receiving ocrelizumab. An increased risk of infections (including serious and fatal bacterial, fungal, and new or reactivated viral infections) has been observed in patients during and following completion of treatment with anti-CD20 B-cell depleting therapies.

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 was not associated with an increased risk of serious infections in MS patients in controlled trials.

Ocrelizumab increases the risk for upper respiratory tract infections, lower respiratory tract infections, skin infections, and herpes-related infections. Delay administration of ocrelizumab in patients with an active infection until the infection has resolved.

Respiratory Tract Infections

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.

Herpes

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. 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%).

Serious cases of infections caused by herpes simplex virus and varicella zoster virus, including central nervous system infections (encephalitis and meningitis), intraocular infections, and disseminated skin and soft tissue infections, have been reported in the postmarketing setting in multiple sclerosis patients receiving ocrelizumab. Serious herpes virus infections may occur at any time during treatment with ocrelizumab. Some cases were life-threatening.

If serious herpes infections occur, treatment with ocrelizumab should be discontinued or withheld until the infection has resolved, and appropriate treatment should be administered.

Hepatitis B Virus Reactivation

Hepatitis B virus (HBV) reactivation has been reported in MS patients treated with ocrelizumab in the postmarketing setting. Fulminant hepatitis, hepatic failure, and death caused by HBV reactivation have occurred in patients treated with anti-CD20 antibodies. Perform HBV screening in all patients before initiation of treatment with ocrelizumab. Do not administer ocrelizumab to patients with active HBV confirmed by positive results for HBsAg and anti-HB tests. 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.

Possible Increased Risk of Immunosuppressant Effects With Other Immunosuppressants

When initiating treatment with ocrelizumab after an immunosuppressive therapy or initiating an immunosuppressive therapy after ocrelizumab-containing products, consider the potential for increased immunosuppressive effect. Treatment with ocrelizumab has not been studied in combination with other MS therapies.

Vaccinations

Administer all immunizations according to immunization guidelines at least 4 weeks prior to initiation of ocrelizumab treatment for live or live-attenuated vaccines and, whenever possible, at least 2 weeks prior to initiation of ocrelizumab treatment for non-live vaccines. Ocrelizumab may interfere with the effectiveness of non-live vaccines. The safety of immunization with live or live-attenuated vaccines following treatment with ocrelizumab has not been studied, and vaccination with live-attenuated or live vaccines is not recommended during treatment and until B-cell repletion.

Vaccination of Infants Born to Mothers Treated With Ocrelizumab Products During Pregnancy

In infants of mothers exposed to ocrelizumab during pregnancy, do not administer live or live-attenuated vaccines before confirming the recovery of B-cell counts as measured by CD19+ B-cells. Depletion of B-cells in these infants may increase the risks from live or live-attenuated vaccines.

You may administer non-live vaccines, as indicated, prior to recovery from B-cell depletion, but you should consider assessing vaccine immune responses, including consultation with a qualified specialist, to assess whether a protective immune response was mounted.

Progressive Multifocal Leukoencephalopathy

Cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients with MS treated with ocrelizumab in the postmarketing setting. PML is an opportunistic viral infection of the brain caused by the JC virus (JCV) that typically occurs only in patients who are immunocompromised, and that usually leads to death or severe disability. PML has occurred in ocrelizumab-treated patients who had not been treated previously with natalizumab, (which has a known association with PML), were not taking any immunosuppressive or immunomodulatory medications associated with risk of PML prior to or concomitantly with ocrelizumab and did not have any known ongoing systemic medical conditions resulting in compromised immune system function.

JCV infection resulting in PML has also been observed in patients treated with other anti-CD20 antibodies and other MS therapies.

At the first sign or symptom suggestive of PML, withhold treatment with ocrelizumab-containing products and perform an appropriate diagnostic evaluation. 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. 

Magnetic resonance imaging (MRI) findings may be apparent before clinical signs or symptoms of PML. Monitoring with MRI for signs consistent with PML may be useful, and any suspicious findings should lead to further investigation to allow for an early diagnosis of PML, if present. If PML is confirmed, treatment with ocrelizumab should be discontinued.

Reduction in Immunoglobulins

As expected with any B-cell depleting therapy, decreased immunoglobulin levels are observed with ocrelizumab treatment. The pooled data of OCREVUS clinical studies (RMS and PPMS) and their open-label extensions (up to approximately 7 years of exposure) have shown an association between decreased levels of immunoglobulin G (IgG<LLN) and increased rates of serious infections. Monitor the levels of quantitative serum immunoglobulins during treatment with ocrelizumab and after discontinuation of treatment, until B-cell repletion, and especially in the setting of recurrent serious infections. Consider discontinuing treatment with ocrelizumab in patients with serious opportunistic or recurrent serious infections, and if prolonged hypogammaglobulinemia requires treatment with intravenous immunoglobulins.

Malignancies

An increased risk of malignancy with ocrelizumab 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.

Immune-Mediated Colitis

Immune-mediated colitis, which can present as a severe and acute-onset form of colitis, has been reported in patients receiving ocrelizumab in the postmarketing setting. Some cases of colitis were serious, requiring hospitalization, with a few patients requiring surgical intervention. Systemic corticosteroids were required in many of these patients. The time from treatment initiation to onset of symptoms in these cases ranged from a few weeks to years. Monitor patients for immune-mediated colitis during ocrelizumab treatment and evaluate promptly if signs and symptoms that may indicate immune-mediated colitis, such as new or persistent diarrhea or other gastrointestinal signs and symptoms, occur.

Liver Injury

Clinically significant liver injury, without findings of viral hepatitis, has been reported in the postmarketing setting in patients treated with anti-CD20 B-cell depleting therapies approved for the treatment of MS, including ocrelizumab. Signs of liver injury, including markedly elevated serum hepatic enzymes with elevated total bilirubin, have occurred from weeks to months after administration.

Patients treated with ocrelizumab found to have an alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 3x the upper limit of normal (ULN) with serum total bilirubin greater than 2x ULN are potentially at risk for severe drug-induced liver injury.

Obtain liver function tests prior to initiating treatment with ocrelizumab, and monitor for signs and symptoms of any hepatic injury during treatment. Measure serum aminotransferases, alkaline phosphatase, and bilirubin levels promptly in patients who report symptoms that may indicate liver injury, including new or worsening fatigue, anorexia, nausea, vomiting, right upper abdominal discomfort, dark urine, or jaundice. If liver injury is present and an alternative etiology is not identified, discontinue ocrelizumab.

Use in Specific Populations
Pregnancy

There are no adequate data on the developmental risk associated with use of ocrelizumab in pregnant women. There are no data on B-cell levels in human neonates following maternal exposure to ocrelizumab-containing products. However, transient peripheral B-cell depletion and lymphocytopenia have been reported in infants born to mothers exposed to other anti-CD20 antibodies during pregnancy. Ocrelizumab is a humanized monoclonal antibody of an immunoglobulin G1 subtype and immunoglobulins are known to cross the placental barrier.

Lactation

There are no data on the presence of ocrelizumab or hyaluronidase 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 ocrelizumab and any potential adverse effects on the breastfed infant from ocrelizumab or from the underlying maternal condition.

Females and Males of Reproductive Potential

Women of childbearing potential should use effective contraception while receiving ocrelizumab and for 6 months after the last dose of ocrelizumab. Instruct patients that if they are pregnant or plan to become pregnant while taking OCREVUS or OCREVUS ZUNOVO, they should inform their healthcare provider.

Most Common Adverse Reactions

In patients treated with OCREVUS:

  • RMS: The most common adverse reactions (≥10% and >REBIF): upper respiratory tract infections and infusion reactions
  • PPMS: The most common adverse reactions (≥10% and >placebo): upper respiratory tract infections, infusion reactions, skin infections, and lower respiratory tract infections

The most common adverse reaction observed with OCREVUS ZUNOVO in patients with RMS and PPMS was injection reactions (incidence of 49%).

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555.

Please see additional Important Safety Information throughout and click here for full OCREVUS Prescribing Information and Medication Guide. For OCREVUS ZUNOVO, click here for full Prescribing Information and Medication Guide.

    • OCREVUS [prescribing information]. South San Francisco, CA: Genentech, Inc. 2025.

      OCREVUS [prescribing information]. South San Francisco, CA: Genentech, Inc. 2025.

    • Hauser SL, Giovannoni G, Filippi M, et al. The patient impact of 11 years of ocrelizumab treatment in multiple sclerosis: long-term data from the phase III OPERA and ORATORIO studies. Poster presented at: 40th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS); September 18-20, 2024; Copenhagen, Denmark. Poster P1664.

      Hauser SL, Giovannoni G, Filippi M, et al. The patient impact of 11 years of ocrelizumab treatment in multiple sclerosis: long-term data from the phase III OPERA and ORATORIO studies. Poster presented at: 40th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS); September 18-20, 2024; Copenhagen, Denmark. Poster P1664.

    • Hauser SL, Bar-Or A, Comi G, et al. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. Supplementary Appendix. N Engl J Med. 2017;376:221-34. doi:10.1056/NEJMoa1601277

      Hauser SL, Bar-Or A, Comi G, et al. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. Supplementary Appendix. N Engl J Med. 2017;376:221-34. doi:10.1056/NEJMoa1601277

    • Hauser SL, Bar-Or A, Comi G, et al; OPERA I and OPERA II Clinical Investigators. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med. 2017;376(3):221-234. doi:10.1056/NEJMoa1601277

      Hauser SL, Bar-Or A, Comi G, et al; OPERA I and OPERA II Clinical Investigators. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med. 2017;376(3):221-234. doi:10.1056/NEJMoa1601277

    • Hauser SL, Kappos L, Montalban X, et al. Long-term reduction in 48-week confirmed disability progression after 5 years of ocrelizumab treatment in patients with relapsing multiple sclerosis. Presented at: 5th Congress of the European Academy of Neurology (EAN); June 29-July 2, 2019; Oslo, Norway. ePoster EPO1250.

      Hauser SL, Kappos L, Montalban X, et al. Long-term reduction in 48-week confirmed disability progression after 5 years of ocrelizumab treatment in patients with relapsing multiple sclerosis. Presented at: 5th Congress of the European Academy of Neurology (EAN); June 29-July 2, 2019; Oslo, Norway. ePoster EPO1250.

    • Data on File. Genentech, Inc. April 2019.

      Data on File. Genentech, Inc. April 2019.

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