Subject:
Ocrelizumab (Ocrevus)
Description:
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IMPORTANT NOTE:
The purpose of this policy is to provide general information applicable to the administration of health benefits that Horizon Blue Cross Blue Shield of New Jersey and Horizon Healthcare of New Jersey, Inc. (collectively “Horizon BCBSNJ”) insures or administers. If the member’s contract benefits differ from the medical policy, the contract prevails. Although a service, supply or procedure may be medically necessary, it may be subject to limitations and/or exclusions under a member’s benefit plan. If a service, supply or procedure is not covered and the member proceeds to obtain the service, supply or procedure, the member may be responsible for the cost. Decisions regarding treatment and treatment plans are the responsibility of the physician. This policy is not intended to direct the course of clinical care a physician provides to a member, and it does not replace a physician’s independent professional clinical judgment or duty to exercise special knowledge and skill in the treatment of Horizon BCBSNJ members. Horizon BCBSNJ is not responsible for, does not provide, and does not hold itself out as a provider of medical care. The physician remains responsible for the quality and type of health care services provided to a Horizon BCBSNJ member.
Horizon BCBSNJ medical policies do not constitute medical advice, authorization, certification, approval, explanation of benefits, offer of coverage, contract or guarantee of payment.
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On March 28, 2017, the FDA approved Ocrelizumab (Ocrevus), a CD20-directed cytolytic antibody, indicated for the treatment of patients with relapsing or primary progressive forms of multiple sclerosis. The precise mechanism by which ocrelizumab exerts its therapeutic effects in multiple sclerosis is unknown, but is presumed to involve binding to CD20, a cell surface antigen present on pre-B and mature B lymphocytes. Following cell surface binding to B lymphocytes, ocrelizumab results in antibody-dependent cellular cytolysis and complement-mediated lysis.
The FDA approval of Ocrevus was based on two randomized, double-blind, double-dummy, active comparator-controlled clinical trials of identical design, in patients with relapsing multiple sclerosis (RMS) treated for 96 weeks (Study 1 and Study 2). The dose of Ocrevus was 600 mg every 24 weeks (initial treatment was given as two 300 mg IV infusions administered 2 weeks apart, and subsequent doses were administered as a single 600 mg IV infusion) and placebo subcutaneous injections were given 3 times per week. The dose of Rebif, the active comparator, was 44 mcg given as subcutaneous injections 3 times per week and placebo IV infusions were given every 24 weeks. Both studies included patients who had experienced at least one relapse within the prior year, or two relapses within the prior two years, and had an Expanded Disability Status Scale (EDSS) score from 0 to 5.5. The primary outcome of both studies was the annualized relapse rate (ARR). Additional outcome measures included the proportion of patients with confirmed disability progression, the mean number of MRI T1 gadolinium (Gd)-enhancing lesions at Weeks 24, 48, and 96, and new or enlarging MRI T2 hyperintense lesions.
In Study 1, 410 patients were randomized to Ocrevus and 411 to Rebif; 11% of Ocrevus-treated and 17% of Rebif-treated patients did not complete the 96-week double-blind treatment period. In Study 2, 417 patients were randomized to Ocrevus and 418 to Rebif; 14% of Ocrevus-treated and 23% of Rebif-treated patients did not complete the 96-week double-blind treatment period. In both studies, Ocrevus significantly lowered the annualized relapse rate and the proportion of patients with disability progression confirmed at 12 weeks after onset compared to Rebif. The relative reduction of ARR was 46% (p<0.0001) in Study 1 and 47% (p<0.0001) in Study 2. The primary population for analysis of confirmed disability progression was the pooled population from Studies 1 and 2; the proportion of patients with 12-week confirmed disability progression was 9.8% in the Ocrevus group versus 15.2% in the Rebif group, with a risk reduction of 40% in the pooled analysis (p=0.0006).
Study 3 was a randomized, double-blind, placebo-controlled clinical trial in patients with primary progressive multiple sclerosis (PPMS). Patients were randomized 2:1 to receive either Ocrevus 600 mg or placebo as two 300 mg intravenous infusions 2 weeks apart every 24 weeks for at least 120 weeks. Study 3 randomized 488 patients to Ocrevus and 244 to placebo; 21% of Ocrevus-treated patients and 34% of placebo-treated patients did not complete the trial. The primary outcome was the time to onset of disability progression attributable to MS confirmed to be present at the next neurological assessment at least 12 weeks later. Additional outcome measures included timed 25-foot walk, and percentage change in T2 hyperintense lesion volume. The time to onset of disability progression confirmed at 12 weeks after onset was significantly longer for Ocrevus-treated patients than for placebo-treated patients, with a risk reduction of 24% (p=0.0321).
Policy:
(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance)
The requirements of the Horizon BCBSNJ Ocrelizumab (Ocrevus) Program may require a precertification/prior authorization via MagellanRx Management. These requirements are member-specific: please verify member eligibility and requirements through the Horizon Provider Portal (www.horizonblue.com/provider). Ordering clinicians should request pre-certification from MagellanRx Management at ih.magellanrx.com or call 1-800-424-4508 (when applicable).
1. Ocrevus (ocrelizumab) is considered medically necessary for the treatment of relapsing multiple sclerosis (RMS) that includes: clinically isolated syndrome (CIS), relapsing-remitting disease (RRMS), and active secondary progressive disease (SPMS), in patients 18 years or older when all of the following criteria are met:
a. Member has a diagnosis of multiple sclerosis and has magnetic resonance imaging (MRI) of the brain showing abnormalities consistent with multiple sclerosis
b. Member has at least two documented clinical relapses within the previous 2 years or one clinical relapse within the year before initiating therapy with Ocrevus
c. Member has neurologic stability for at least 30 days before starting therapy with Ocrevus
d. Member does not have known presence of other neurological disorders which may mimic multiple sclerosis
e. Member is not currently being treated with another disease modifying MS therapy (e.g. interferon beta preparations, dimethyl fumarate, glatiramer acetate, natalizumab, fingolimod cladribine, siponimod, or teriflunomide) or, if the member is currently on another therapy, the other medication will be discontinued prior to starting therapy with Ocrevus
f. Member will not be receiving concomitant therapy with cyclophosphamide, azathioprine, mycophenolate mofetil, cyclosporine, methotrexate, any B-cell targeted therapy (e.g., rituximab, ocrelizumab, atacicept, belimumab, or ofatumumab), or other immunosuppressive medication
g. Member has not had live-attenuated or live vaccines within 6 weeks prior to initiation of treatment with Ocrevus
h. Member does not have an active infection
i Member must have hepatitis B virus screening before the first dose and negative results for HBsAg and anti-HBV tests
j. Member does not have history of progressive multifocal leukoencephalopathy
k. Member does not have history of or currently active primary or secondary immunodeficiency
2. Ocrevus (ocrelizumab) is considered medically necessary for the treatment of primary progressive multiple sclerosis (PPMS) in patients 18 years or older when the following criteria are met:
a. Member has a diagnosis of primary progressive multiple sclerosis
b. Member has a score on the pyramidal functions component of the Functional Systems Scale of at least 2
c. Member has a documented history or the presence at screening of an elevated IgG index or at least one IgG oligoclonal band detected in the cerebrospinal fluid
d. Member does not have known presence of other neurological disorders which may mimic multiple sclerosis
e. Member is not currently being treated with another disease modifying MS therapy (e.g. interferon beta preparations, dimethyl fumarate, glatiramer acetate, natalizumab, fingolimod cladribine, siponimod, or teriflunomide) or, if the member is currently on another therapy, the other medication will be discontinued prior to starting therapy with Ocrevus
f. Member will not be receiving concomitant therapy with cyclophosphamide, azathioprine, mycophenolate mofetil, cyclosporine, methotrexate, any B-cell targeted therapy (e.g., rituximab, ocrelizumab, atacicept, belimumab, or ofatumumab), or other immunosuppressive medication
g. Member has not had live-attenuated or live vaccines within 6 weeks prior to initiation of treatment with Ocrevus
h. Member does not have an active infection
i. Member must have hepatitis B virus screening before the first dose and negative results for HBsAg and anti-HBV tests
j. Member does not have history of cancer, including solid tumors and hematological malignancies (except for basal cell, in situ squamous cell carcinomas of the skin and in situ carcinoma of the cervix that have been excised and resolved)
[INFORMATION NOTE: The Expanded Disability Status Scale (EDSS) ranges from 0 to 10.0, with higher scores indicating greater disability. The Functional Systems Scale ranges from 0 to 6, with higher scores indicating greater disability.]
3. When Ocrevus (ocrelizumab) is considered medically necessary, initial therapy will be approved for 6 months at the following FDA-approved dose:
a. Start dose: 300 mg intravenous infusion, followed two weeks later by a second 300 mg intravenous infusion
4. Continuation of Ocrevus (ocrelizumab) will be approved every 6 months at the FDA-approved dose of 600 mg intravenous infusion every 6 months when the member meets all of the following criteria:
a. Continues to meet initial review criteria; AND
b. There are no unacceptable toxicities, including but not limited to, severe infusion reactions, severe infections, and malignancy; AND
c. There is documented evidence of efficacy
i. For the treatment of relapsing multiple sclerosis (RMS), there is evidence of disease stability and/or improvement (i.e., Expanded Disability Status Scale [EDSS] scores, decrease in relapses, no MRI progression of disease)
ii. For the treatment of primary progressive multiple sclerosis (PPMS), there is evidence of maintenance of baseline or slowed disease progression
[INFORMATIONAL NOTE: As per the FDA approved package insert, premedication is recommended prior to each intravenous infusion of Ocrevus. Pre-medicate with 100 mg of methylprednisolone (or an equivalent corticosteroid) administered intravenously approximately 30 minutes prior to each Ocrevus infusion to reduce the frequency and severity of infusion reactions. Pre-medicate with an antihistamine (e.g., diphenhydramine) approximately 30-60 minutes prior to each Ocrevus infusion to further reduce the frequency and severity of infusion reactions. The addition of an antipyretic (e.g., acetaminophen) may also be considered.
The most common adverse reactions seen with Ocrevus were:
-RMS (incidence ≥10% and > REBIF): upper respiratory tract infections and infusion reactions
-PPMS (incidence ≥10% and > placebo): upper respiratory tract infections, infusion reactions, skin infections, and lower respiratory tract 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.
Although no cases of Progressive Multifocal Leukoencephalopathy (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.
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.]
5. Ocrevus (ocrelizumab) for the treatment of other conditions/diseases is considered investigational, including but not limited to:
· Rheumatoid Arthritis
· Non-Hodgkin’s Lymphoma
· Autoimmune Encephalitis
· Systemic Lupus Erythematosus
· Lupus Nephritis
Medicare Coverage
There is no National Coverage Determination (NCD) or Local Coverage Determination (LCD) for jurisdiction JL for Ocrelizumab (Ocrevus). Therefore, Medicare Advantage Products will follow the Horizon BCBSNJ medical policy.
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Horizon BCBSNJ Medical Policy Development Process:
This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.
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Index:
Ocrelizumab (Ocrevus)
Ocrevus (Ocrelizumab)
Multiple Sclerosis, Ocrelizumab (Ocrevus) for
References:
1. Ocrevus™ (ocrelizumab). [Prescribing Information]. Genentech, Inc. South San Francisco, CA. May 2020.
2. Hauser SL, Bar-Or A, Comi G, et al. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med. 2017 Jan 19;376(3):221-234.
3. Montalban X, Hauser SL, Kappos L, et al. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl J Med. 2017 Jan 19;376(3):209-220.
4. Ocrevus™ (ocrelizumab). [AMCP Dossier]. Genentech, Inc. April 2017.
5. ClinicalTrials.gov. A Study of Ocrelizumab in Comparison With Interferon Beta-1a (Rebif) in Participants With Relapsing Multiple Sclerosis. Available from: https://clinicaltrials.gov/ct2/show/NCT01247324?term=NCT01247324&rank=1. Accessed April 29, 2017.
6. ClinicalTrials.gov. A Study of Ocrelizumab in Comparison With Interferon Beta-1a (Rebif) in Participants With Relapsing Multiple Sclerosis. Available from: https://clinicaltrials.gov/ct2/show/NCT01412333?term=NCT01412333&rank=1. Accessed November 15, 2019.
7. ClinicalTrials.gov. A Study of Ocrelizumab in Participants With Primary Progressive Multiple Sclerosis. Available from: https://clinicaltrials.gov/ct2/show/NCT01194570?term=NCT01194570&rank=1. Accessed November 15, 2019.
8. Ocrevus . Clinicaltrial.gov. Accessed on 2/24/19 . Available at: https://clinicaltrials.gov/ct2/results?cond=&term=ocrevus&cntry=&state=&city=&dist=
Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)
CPT*
HCPCS
J2350
* CPT only copyright 2020 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.
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Medical policies can be highly technical and are designed for use by the Horizon BCBSNJ professional staff in making coverage determinations. Members referring to this policy should discuss it with their treating physician, and should refer to their specific benefit plan for the terms, conditions, limitations and exclusions of their coverage.
The Horizon BCBSNJ Medical Policy Manual is proprietary. It is to be used only as authorized by Horizon BCBSNJ and its affiliates. The contents of this Medical Policy are not to be copied, reproduced or circulated to other parties without the express written consent of Horizon BCBSNJ. The contents of this Medical Policy may be updated or changed without notice, unless otherwise required by law and/or regulation. However, benefit determinations are made in the context of medical policies existing at the time of the decision and are not subject to later revision as the result of a change in medical policy
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