Last Review Date: 10/03/2024

Date of Origin: 10/03/2024

Dates Reviewed: 10/2024

1. Length of Authorization

Coverage will be provided for 12 months and may be renewed annually thereafter.

2. Dosing Limits

A. Quantity Limit (max daily dose) [NDC unit]:

• Ocrevus 920 mg ocrelizumab and 23,000 units hyaluronidase per 23 mL solution in a single-dose vial: 1 vial per 6 months

B. Max Units (per dose and over time) [HCPCS Unit]:

• 920 mg ocrelizumab (and 23,000 units hyaluronidase) every 6 months

3. Initial Approval Criteria ¹

Coverage is provided in the following conditions:

• Patient is at least 18 years of age; AND
• Patient has been screened for the presence of Hepatitis B virus (HBV) prior to initiating treatment AND does not have active disease (i.e., positive HBsAg and anti-HBV tests); AND
• Patient has had baseline serum immunoglobulins assessed; AND
• Patient does not have a history of life-threatening administration reactions to ocrelizumab; AND

Universal Criteria ¹

• Patient will not receive live or live-attenuated vaccines while on therapy or within 4 weeks prior to initiation of treatment; AND
• Patient does not have an active infection; AND
• Must be used as single agent therapy; AND
• Patient has not received a dose of ocrelizumab or ublituximab within the past 5 months; AND

Multiple Sclerosis † ^1,7,11

• Patient must have a confirmed diagnosis of multiple sclerosis (MS) as documented by laboratory report (i.e., MRI); AND
  • Patient has a diagnosis of a relapsing form of MS [i.e., relapsing-remitting MS (RRMS)*, active secondary progressive disease (SPMS)**, or clinically isolated syndrome (CIS)***]; OR
  • Patient has a diagnosis of primary progressive MS (PPMS)****; AND

• • Patient is less than 65 years of age; AND
  • Patient has an expanded disability status scale (EDSS) score of ≤ 6.5

† FDA Approved Indication(s); ‡ Compendium Recommended Indication(s); Ф Orphan Drug

4. Renewal Criteria ^1,6,10,14

Coverage can be renewed based on the following criteria:

• Patient continues to meet the universal and other indication-specific relevant criteria identified in section III; AND
• Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: severe infusion reactions, severe infections, progressive multifocal leukoencephalopathy malignancy, hypogammaglobulinemia, immune-mediated colitis, etc.; AND
• Continuous monitoring of response to therapy indicates a beneficial response* [manifestations of MS disease activity include, but are not limited to, an increase in annualized relapse rate (ARR), development of new/worsening T2 hyperintensities or enhancing lesions on brain/spinal MRI, and progression of sustained impairment as evidenced by expanded disability status scale (EDSS), timed 25-foot walk (T25-FW), 9-hole peg test (9-HPT)]

Note: patients with primary progressive MS generally do not have clinical relapses and do not typically develop new lesions on MRI

PPMS

• Patient continues to be ambulatory, defined as an EDSS score of <7.5

5. Dosage/Administration ¹

6. Billing Code/Availability Information

HCPCS:

• J3590 – Unclassified biologics

NDC:

• Ocrevus Zunovo 920 mg and 23,000 units/23 mL (40 mg and 1,000 units/mL) single-dose vial: 50242-0554-xx

7. References

1. Ocrevus Zunovo [package Insert]. South San Francisco, CA; Genentech, Inc.; September 2024. Accessed September 2024.
2. 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.
3. 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.
4. Gawronski KM, Rainka MM, Patel MJ, Gengo FM. Treatment Options for Multiple Sclerosis: Current and Emerging Therapies. Pharmacotherapy. 2010; 30(9):916-927.
5. Goodin DS, Frohman EM, Garmany GP Jr, et al. Disease modifying therapies in multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. Neurology. 2002 Jan 22; 58(2):169-78.
6. Freedman MS, Selchen D, Arnold DL, et al. Treatment optimization in MS: Canadian MS Working Group updated recommendations. Can J Neurol Sci. 2013 May;40(3):307-23.
7. Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 Revisions to the McDonald criteria. Ann Neurol. 2011 Feb; 69(2): 292–302. doi:  10.1002/ana.22366.
8. Lublin FD, Reingold SC, Cohen JA, et al. Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology. 2014 Jul 15;83(3):278-86.
9. Multiple Sclerosis Coalition. The use of disease-modifying therapies in multiple sclerosis: principles and current evidence. 2019 September. http://www.nationalmssociety.org/getmedia/5ca284d3-fc7c-4ba5-b005-ab537d495c3c/DMT_Consensus_MS_Coalition_color. Accessed August 2023.
10. Rae-Grant, A, Day GS, Marrie RA, et al. Practice guideline recommendations summary: Disease-modifying therapies for adults with multiple sclerosis. Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology® 2018;90:777-788.
11. Thompson AJ, Banwell BL, Barkhof F, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018 Feb;17(2):162-173. doi: 10.1016/S1474-4422(17)30470-2.
12. Kappos L, Bar-Or A, Cree BAC, et al. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study. Lancet. 2018;391(10127):1263. Epub 2018 Mar 23.
13. Lorscheider J, Buzzard K, Jokubaitis V, et al, on behalf of the MSBase Study Group. Defining secondary progressive multiple sclerosis. Brain, Volume 139, Issue 9, September 2016, Pages 2395–2405, https://doi.org/10.1093/brain/aww173.
14. Freedman MS, Devonshire V, Duquette P, et al; Canadian MS Working Group. Treatment Optimization in Multiple Sclerosis: Canadian MS Working Group Recommendations. Can J Neurol Sci. 2020 Jul;47(4):437-455. doi: 10.1017/cjn.2020.66.
15. Cree BAC, Arnold DL, Chataway J, et al. Secondary Progressive Multiple Sclerosis: New Insights. Neurology. 2021 Aug 24;97(8):378-388. doi: 10.1212/WNL.0000000000012323. Epub 2021 Jun 4.

Appendix 1 – Covered Diagnosis Codes

Appendix 2 – Centers for Medicare and Medicaid Services (CMS)

The preceding information is intended for non-Medicare coverage determinations. Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determinations (NCDs) and/or Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. Local Coverage Articles (LCAs) may also exist for claims payment purposes or to clarify benefit eligibility under Part B for drugs which may be self-administered. The following link may be used to search for NCD, LCD, or LCA documents https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications, including any preceding information, may be applied at the discretion of the health plan.

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCD/LCA):  N/A