OCREVUS® (ocrelizumab) for Relapsing Multiple Sclerosis (RMS)

OCREVUS® (ocrelizumab) has safety and efficacy in RMS

Head-to-head clinical trials evaluating more than 1600 patients

RMS OPERA I and II study design^4,6

The efficacy and safety of OCREVUS (ocrelizumab) in RMS were studied vs Rebif in 2 double-blind, double-dummy trials evaluating more than 1600 patients for 2 years.

See Study Design

5 key clinical efficacy endpoints^4,6

OCREVUS demonstrated superior clinical results vs Rebif across 5 key endpoints over 2 years.

Explore RMS Data

OCREVUS safety profile for RMS^2-4

The safety of OCREVUS for RMS was studied in the 2-year controlled OPERA I and II clinical trials and observed in over 4 years of open-label extension study.

View Latest Safety Data

RMS=relapsing multiple sclerosis.

Indications

OCREVUS is 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

OCREVUS is contraindicated in patients with active hepatitis B virus infection and in patients with a history of life-threatening infusion reaction to OCREVUS.

Warnings and Precautions

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, tachycardia, and anaphylaxis. 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.

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. 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.

Infections

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.

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 OCREVUS. Serious herpes virus infections may occur at any time during treatment with OCREVUS. Some cases were life-threatening.

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

Progressive Multifocal Leukoencephalopathy (PML)

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).

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. 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 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.

Vaccinations

Administer all immunizations according to immunization guidelines at least 4 weeks prior to initiation of OCREVUS for live or live-attenuated vaccines and, whenever possible, at least 2 weeks prior to initiation of OCREVUS for non-live vaccines. OCREVUS may interfere with the effectiveness of non-live vaccines. 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.

Vaccination of Infants Born to Mothers Treated with OCREVUS During Pregnancy

In infants of mothers exposed to OCREVUS 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 should consider assessing vaccine immune responses, including consultation with a qualified specialist, to assess whether a protective immune response was mounted.

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.

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.

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.

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%).

For additional safety information, please see the full Prescribing Information and Medication Guide.

References

1.

Data on file. Genentech, Inc. April 2019.

2.

Hauser SL, Brochet B, Montalban X, et al. Long-term reduction of relapse rate and confirmed disability progression after 5 years of ocrelizumab treatment in patients with relapsing multiple sclerosis. Presented at: 34th Congress of the European Committee for Treatment and Research in Multiple Sclerosis; October 10-12, 2018; Berlin, Germany.

3.

Hauser SL, Kappos L, Montalban X, et al. Safety of ocrelizumab in multiple sclerosis: updated analysis in patients with relapsing and primary progressive multiple sclerosis. Poster presented at: the 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS); September 11-13, 2019; Stockholm, Sweden.

4.

OCREVUS [prescribing information]. South San Francisco, CA: Genentech, Inc. 2020.

5.

FDA approves new drug to treat multiple sclerosis [press release]. Silver Spring, MD: Food and Drug Administration; March 29, 2017.

6.

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.

7.

Hauser SL, Kappos L, Montalban X, et al. Safety of ocrelizumab in multiple sclerosis: updated analysis in patients with relapsing and primary progressive multiple sclerosis. Presented at: 34th Congress of the European Committee for Treatment and Research in Multiple Sclerosis; October 10-12, 2018; Berlin, Germany.

8.

De Stefano N, Giorgia A, Battaglini M, et al. Assessing brain atrophy rates in a large population of untreated multiple sclerosis subtypes. Neurology. 2010;74(23);1868-1876.

9.

Fox RJ, Cohen JA. Multiple sclerosis: the importance of early recognition and treatment. Cleve Clin J Med. 2001;68(2):157-171.

10.

Wijnands JMA, Kingwell E, Zhu F, et al. Health-care use before a first demyelinating event suggestive of a multiple sclerosis prodrome: a matched cohort study. Lancet Neurol. 2017;16(6):445-451.

11.

Confavreux C, Vukusic S. Natural history of multiple sclerosis: a unifying concept. Brain. 2006;129(3):606-616.

12.

Cree BAC, Hollenbach JA, Bove R, et al. Silent progression in disease activity-free relapsing multiple sclerosis. Ann Neurol. 2019;85(5):653-666.

13.

Kantarci OH, Lebrun C, Siva A, et al. Primary progressive multiple sclerosis evolving from radiologically isolated syndrome. Ann Neurol. 2016;79(2):288-294.

14.

Okuda DT, Siva A, Kantarci O, et al. Radiologically isolated syndrome: 5-year risk for an initial clinical event. PLoS One. 2014 Mar 5;9(3):e90509.

15.

Krieger SC, Cook K, De Nino S, Fletcher M. The topographical model of multiple sclerosis: a dynamic visualization of disease course. Neurol Neuroimmunol Neuroinflamm. 2016;3(5):e279.

16.

Zeydan B, Kantarci OH. Progressive forms of multiple sclerosis: distinct entity or age-dependent phenomena. Neurol Clin. 2018;36(1):163-171.

17.

Krieger SC, Sumowski J. New insights into multiple sclerosis clinical course from the topographical model and functional reserve. Neurol Clin. 2018;36(1):13-25.

18.

De Stefano N, Narayan S, Francis GS, et al. Evidence of axonal damage in the early stages of multiple sclerosis and its relevance to disability. Arch Neurol. 2001;58(1)65-70.

19.

Dutta R, Trapp BD. Mechanisms of neuronal dysfunction and degeneration in multiple sclerosis. Prog Neurobiol. 2011;93(1):1-12.

20.

Singh S, Dallenga T, Winkler A, et al. Relationship of acute axonal damage, Wallerian degeneration, and clinical disability in multiple sclerosis. J Neuroinflammation. 2017;14(1):57.

21.

Hawker K. Progressive multiple sclerosis: characteristics and management. Neurol Clin. 2011;29(2):423-434.

22.

Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33(11):1444-1452.

23.

Akbar N, Honarmand K, Kou N, et al. Validity of a computerized version of the symbol digit modalities test in multiple sclerosis. J Neurol. 2011;258(3):373-379.

24.

Watson TM, Ford E, Worthington E, Lincoln NB. Validation of mood measures for people with multiple sclerosis. Int J MS Care. 2014;16(2):105-109.

25.

Javůrková A, Zimová D, Tomašovičová K, et al. Cognitive deficits and neuropsychological assessment in multiple sclerosis. In Gonzalez-Quevedo, ed. Trending Topics in Multiple Sclerosis. Rijeka, Croatia: IntechOpen; 2016; chapter 9.

26.

van Munster CE, Uitdehaag BM. Outcome measures in clinical trials for multiple sclerosis. CNS Drugs. 2017 Mar;31(3):217-236.

27.

Kremenchutzky M, Rice GP, Baskerville J, et al. The natural history of multiple sclerosis: a geographically based study 9: observations on the progressive phase of the disease. Brain. 2006;129(Pt 3):584-594.

28.

Confavreux C, Vukusic S. Accumulation of irreversible disability in multiple sclerosis: from epidemiology to treatment. Clin Neurol Neurosurg. 2006;108(3):327-332.

29.

Debouverie M, Pittion-Vouyovitch S, Louis S, Guillemin F, et al. Natural history of multiple sclerosis in a population-based cohort. Eur J Neurol. 2008;15(9):916-921.

30.

Baker D, Marta M, Pryce G, Giovannoni G, Schmierer K. Memory B cells are major targets for effective immunotherapy in relapsing multiple sclerosis. EBioMedicine. 2017;16:41-50.

31.

Data on file. Genentech, Inc. May 2019.

32.

Data on file. Genentech, Inc. July 2018.

33.

Turner B, Cree B, Kappos L, et al. Ocrelizumab efficacy in subgroups of patients with relapsing multiple sclerosis. J Neurol. 2019;266(5):1182-1193.

34.

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)(suppl):S6.

35.

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.

36.

Data on file. Genentech, Inc. April 2019.

37.

Kaunzner UW, Gauthier SA. MRI in the assessment and monitoring of multiple sclerosis: an update on best practice. Ther Adv Neurol Disord. 2017;10(6):247-261.

38.

Arnold DL, Kappos L, Hauser SL, et al. Long-term reduction in brain MRI disease activity and atrophy after 5 years of ocrelizumab treatment in patients with relapsing multiple sclerosis. Presented at: 34th Congress of the European Committee for Treatment and Research in Multiple Sclerosis; October 10-12, 2018; Berlin, Germany.

39.

De Seze J, Arnold DL, Bar-Or A, et al. Infusion-related reactions with ocrelizumab in relapsing multiple sclerosis and primary progressive multiple sclerosis. Presented at: 32nd Congress of the European Committee for Treatment and Research of Multiple Sclerosis; September 14-17, 2016; London, United Kingdom.

40.

Centers for Disease Control and Prevention. Women with disabilities and breast cancer screening. https://www.cdc.gov/ncbddd/disabilityandhealth/breast-cancer-screening.html. Accessed August 20, 2019.

41.

American Cancer Society. American Cancer Society guidelines for the early detection of cancer. https://www.cancer.org/healthy/find-cancer-early/cancer-screening-guidelines/american-cancer-society-guidelines-for-the-early-detection-of-cancer.html. Accessed February 15, 2019.

42.

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.

43.

Data on file. Genentech, Inc. March 2020.

RMS OPERA I and II study design 4,6

5 key clinical efficacy endpoints 4,6

OCREVUS safety profile for RMS 2-4

Important Safety Information & Indications

Indications

Contraindications

Warnings and Precautions

Infusion Reactions

Infections

Malignancies

Use in Specific Populations

Pregnancy

Lactation

Females and Males of Reproductive Potential

Most Common Adverse Reactions

References

RMS OPERA I and II study design^4,6

5 key clinical efficacy endpoints^4,6

OCREVUS safety profile for RMS^2-4