Viva Health natalizumab Prior Auth & Coverage

Coverage and Approval Criteria

inv-01: Initial Therapy — Initial Approval Criteria

Prior authorization validity is provided when ALL of the following are met:

Universal initial criteria: Patient must have a contraindication, intolerance, or failure to ONE generic disease-modifying agent prior to consideration of a natalizumab product; AND Member is at least 18 years of age; AND Documented JCV antibody ELISA test within the past 6 months; AND Not used in combination with antineoplastic, immunosuppressant, or immunomodulating agents; AND Member must not have a systemic medical condition resulting in significantly compromised immune system function.

See chunks 4-5 for universal criteria.

MS-specific initial criteria: Member must have a confirmed diagnosis of multiple sclerosis documented by laboratory report (e.g., MRI); AND Member has a relapsing form of multiple sclerosis (relapsing-remitting MS, active secondary progressive MS, or clinically isolated syndrome); AND Used as single-agent therapy.

See chunk 5 for MS criteria.

Crohn's disease-specific initial criteria: Member has moderate to severe active Crohn's disease; AND Physician has assessed baseline disease severity using an objective measure/tool; AND (Documented trial and failure on ONE oral immunosuppressive therapy for at least 3 months unless contraindicated OR Member is already established on biologic or targeted synthetic therapy); AND Documented trial and failure on ONE TNF-inhibitor therapy for at least 3 months unless contraindicated; AND Used as single-agent therapy (not used concurrently with another biologic, targeted synthetic therapy, or immunosuppressant used for Crohn's disease).

See chunk 6 for Crohn's disease criteria.

inv-02: Renewal Therapy — Renewal Criteria

Prior authorization may be renewed when ALL of the following are met:

General renewal requirements: Member continues to meet the universal and other indication-specific relevant criteria identified in initial approval (section III); AND Absence of unacceptable toxicity from the drug (examples include hypersensitivity/antibody formation, hepatotoxicity, signs or symptoms of PML, herpes infections including encephalitis/meningitis, immunosuppression, various infections, hematologic abnormalities such as thrombocytopenia, etc.).

See chunk 8 for general renewal language and examples of unacceptable toxicity.

MS-specific evidence of benefit: Continuous monitoring of response to therapy indicates a beneficial response, demonstrated by fewer relapses, no new/worsening T2 hyperintensities or enhancing lesions on MRI, and no progression of sustained impairment as evidenced by EDSS, T25-FW, or 9-HPT measures.

See chunk 9 for MS monitoring and manifestations of disease activity.

CD-specific renewal timing and evidence: Initial renewal: clinical response and remission of disease by 12 weeks; AND Second renewal: patient tapered off oral corticosteroids within 6 months of starting natalizumab AND evidence of disease response compared to baseline (improvements in endoscopic activity, number of liquid stools, abdominal pain, body weight, hematocrit, extra-intestinal complications, tapering/discontinuation of corticosteroid therapy, use of anti-diarrheal drugs, improvement in biomarkers such as fecal calprotectin or CRP, or improved disease activity score e.g., Harvey-Bradshaw Index); AND All subsequent renewals: patient does not require additional steroid use exceeding 3 months in a calendar year AND continued disease response as described above.

Natalizumab must not be used concurrently with other biologic, targeted synthetic, or immunosuppressant therapies for Crohn’s Disease and should not be given in combination with antineoplastic, immunosuppressant, or immunomodulating agents. For Crohn’s Disease the policy explicitly states not to be used concurrently with another biologic, targeted synthetic therapy, or immunosuppressant (examples include upadacitinib, 6-mercaptopurine, azathioprine, cyclosporine, methotrexate). Similarly, universal criteria require single‑agent use and prohibit combination with antineoplastic or immunomodulating agents for all indications.

The policy content and coverage rules are intended to support non‑Medicare coverage determinations. Where applicable, providers and reviewers must follow Medicare guidance including the Medicare Benefit Policy Manual (Pub. 100‑02), Chapter 15 §50, and any relevant National Coverage Determinations (NCDs), Local Coverage Determinations (LCDs), or Local Coverage Articles (LCAs). Links to CMS resources are provided for searching NCD/LCD/LCA documents, and compliance with those Medicare policies is required when they apply.

Approval requires documentation of required prior therapy trials and baseline testing. Requests lacking required documentation — for example, absence of a documented trial and failure (or contraindication) of the specified prior therapies for the indication, or missing a documented JCV antibody ELISA test within the past 6 months, or missing objective baseline disease assessment (e.g., MRI for MS or objective disease severity tool for Crohn’s) — do not meet medical necessity. Providers should also note that use in patients with systemic medical conditions causing significantly compromised immune function or concurrent prohibited agents may lead to denial.

Initial Authorization Criteria (Drug-specific)

inv-24: Initial Therapy (Drug-specific)

Initial authorization criteria per indication:

Initial MS criteria (drug-specific): Member >= 18 years; confirmed relapsing form of multiple sclerosis documented by laboratory report (e.g., MRI); trial/failure of ONE generic disease-modifying agent prior to natalizumab; used as single-agent therapy; documented JCV antibody ELISA within past 6 months; not used in combination with antineoplastic, immunosuppressant, or immunomodulating agents; member must not have systemic medical condition causing significantly compromised immune function.

Chunks 4-5 provide the drug-specific MS initial criteria.

Initial Crohn's disease criteria (drug-specific): Member >= 18 years; moderate to severe active Crohn's disease with objective baseline severity assessment by physician; documented trial and failure of ONE oral immunosuppressive therapy for >= 3 months unless contraindicated OR member already on biologic/targeted synthetic therapy; AND documented trial and failure of ONE TNF-inhibitor therapy for >= 3 months unless contraindicated; used as single-agent therapy (not concurrently with another biologic, targeted synthetic therapy, or immunosuppressant for Crohn's disease); documented JCV antibody ELISA within past 6 months; member must not have systemic medical condition causing significantly compromised immune function.

Chunk 6 contains Crohn's-specific drug initial criteria.

Continuation / Renewal Criteria

inv-25: Continuation Therapy

Renewal/continuation rules:

Continuation requirements (general): Member must continue to meet universal and indication-specific criteria and demonstrate absence of unacceptable toxicity from natalizumab.

See chunk 8.

MS continuation requirements: Ongoing clinical and radiographic monitoring must indicate beneficial response (fewer relapses, no new/worsening MRI lesions, no progression in disability per EDSS/T25-FW/9-HPT); absence of unacceptable toxicity.

See chunk 9 for MS-specific continuation evidence.

Crohn's disease continuation/renewal requirements: Initial renewal: clinical response/remission by 12 weeks; Second renewal: tapered off oral corticosteroids within 6 months of starting natalizumab AND documented disease response measures (endoscopic activity, stool frequency, abdominal pain, weight regain, hematocrit, extra-intestinal complications, steroid tapering/discontinuation, anti-diarrheal use, biomarker improvement e.g., fecal calprotectin or CRP, or improved disease activity score); Subsequent renewals: steroid use not to exceed 3 months in a calendar year AND continued disease response measures as above.

Provider Requirements and Operational Steps

Prior Authorization

Prior Authorization Required

Prior Authorization Required: Submit a completed prior authorization request with documentation of a covered diagnosis code from Appendix 1 to support the request. Prior authorization validity and renewal cadence: Crohn's Disease — initial PA provided for 12 weeks; renewals may be granted every 6 months (180 days). Multiple Sclerosis — initial PA provided for 12 months (365 days); renewals may be granted every 12 months (365 days).

Provider must include one of the covered ICD-10 diagnosis codes from Appendix 1 (e.g., G35.* for MS; K50.* for Crohn's Disease).
PA duration: Crohn's Disease initial=12 weeks; renewal cadence=every 6 months (180 days).
PA duration: Multiple Sclerosis initial=12 months (365 days); renewal cadence=every 12 months (365 days).

Denial Risk

Combination Therapy / Immunocompromise

Combination therapy and immunocompromise restrictions: Therapy must not be used in combination with antineoplastic, immunosuppressant, or immunomodulating agents. Do not approve when the member has a systemic medical condition that results in significantly compromised immune system function. For Crohn's Disease, do not authorize concurrent use with another biologic, targeted synthetic therapy (e.g., upadacitinib), or immunosuppressant (e.g., 6-mercaptopurine, azathioprine, cyclosporine, methotrexate).

Billing Codes, NDCs, and Diagnosis Codes

HCPCS CodesHCPCSCovered

J2323	Injection, natalizumab, 1 mg; 1 billable unit = 1mg (Tysabri Only)
Q5134	Injection, natalizumab-sztn (tyruko), biosimilar, 1 mg; 1 billable unit = 1 mg (Tyruko Only)

NDCsNDC

64406-0008-xx	Tysabri 300 mg/15 mL single-dose vial: 64406-0008-xx
61314-0543-xx	Tyruko 300 mg/15 mL single-dose vial: 61314-0543-xx

Covered ICD-10 Diagnosis CodesICD-10Covered

G35.A	Relapsing-remitting multiple sclerosis.
G35.B0	Primary progressive multiple sclerosis, unspecified.
G35.B1	Active primary progressive multiple sclerosis.
G35.B2	Non-active primary progressive multiple sclerosis.
G35.C0	Secondary progressive multiple sclerosis, unspecified.
G35.C1	Active secondary progressive multiple sclerosis.
G35.C2	Non-active secondary progressive multiple sclerosis.
G35.D	Multiple sclerosis, unspecified.
K50.00	Crohn's disease of small intestine without complications.
K50.011	Crohn's disease of small intestine with rectal bleeding.

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Max HCPCS units per period

Maximum HCPCS units300 billable units every 28 days

Unit definition1 billable unit = 1 mg (HCPCS units) per policy coding

Assessment periodMeasured over a 28-day (4-week) period

Step Therapy and Prior Trials

Step	Requirement	Minimum trial/failure duration	Notes
1	For Crohn's Disease: trial and failure of ONE oral immunosuppressive therapy (e.g., corticosteroids, methotrexate, azathioprine, 6-mercaptopurine) prior to natalizumab, unless contraindicated; AND documented trial and failure of ONE TNF‑inhibitor therapy (e.g., infliximab, certolizumab, adalimumab) prior to natalizumab	≥ 3 months for each required trial unless contraindicated	Used as single‑agent therapy; not to be used concurrently with another biologic, targeted synthetic therapy, or immunosuppressant for Crohn's Disease
1	For Multiple Sclerosis: trial and failure, intolerance, or contraindication to ONE generic disease‑modifying agent prior to consideration of natalizumab	Not specified as a duration in policy (requirement is prior trial/failure)	Member must be ≥ 18 years of age; documented JCV antibody testing and other universal criteria apply (see Initial Approval Criteria)

NQTL Factor	How step therapy was considered	Conclusion
Indication relevance	Step therapy was evaluated as part of utilization management factors to ensure the prior authorization applies appropriately to indicated uses	Consider for PA
Safety and efficacy	Step requirements (prior trials) are applied where safety/efficacy and clinical appropriateness justify restricting access to natalizumab	Consider for PA
Cost of drug	Cost considerations were reviewed and contributed to using step therapy/prior authorization to manage utilization	Consider for PA
Potential for misuse/abuse	Assessed and not a primary driver for PA or step therapy decisions	Not priority for PA

Quantity Limits and Dosing

Natalizumab (Tysabri / Tyruko) — Quantity Limit

Standard quantity limit300 billable units per 28 days (equivalent to 300 mg q4w)

Dose scheduleAdminister 300 mg intravenously over one hour every four weeks

Applicable productsTysabri (natalizumab) and Tyruko (natalizumab-sztn) biosimilar

Billing Rule

Infusion site of care and administration schedule

Administer natalizumab in an appropriate infusion setting (infusion center, office, or hospital outpatient) as an intravenous infusion of 300 mg over one hour every four weeks.

Products and Biosimilar Information

Billing Rule

Billing codes and NDCs for Tysabri and Tyruko

Billing codes for natalizumab products are provided: HCPCS J2323 for Tysabri and Q5134 for the biosimilar Tyruko; NDCs for each product are also listed in the policy.

HCPCS: J2323 (Tysabri), Q5134 (Tyruko).
NDCs: Tysabri 64406-0008-xx; Tyruko 61314-0543-xx.

Note

Referenced clinical evidence and biosimilar evaluation

Evidence base for natalizumab includes randomized trials and referenced literature (e.g., AFFIRM, SENTINEL) and phase 3 evaluation of a proposed biosimilar (Antelope); biosimilar evidence is considered in references.

Referenced trials: AFFIRM, SENTINEL, and Antelope (phase 3 for proposed biosimilar PB006).

Key Terms and Definitions

PML risk factors

Anti‑JCV antibodiesPresence of anti‑JCV antibodies increases PML risk

Treatment durationLonger treatment duration, especially beyond 2 years, increases PML risk

Prior immunosuppressant therapyPrior treatment with immunosuppressants (e.g., mitoxantrone, azathioprine, methotrexate, cyclophosphamide, mycophenolate mofetil) increases PML risk

Elevated anti‑JCV indexElevated anti‑JCV antibody response index (index > 0.9) is associated with higher PML risk

Relapsing forms of MS

Included diagnosesRelapsing‑remitting MS (RRMS), active secondary progressive MS (active SPMS), and clinically isolated syndrome (CIS) documented by MRI or laboratory report

Clinical Background and Rationale

Natalizumab is a monoclonal antibody indicated for treatment of relapsing forms of multiple sclerosis and for moderate to severe active Crohn’s Disease. It is administered as intravenous infusions at the standard dose of 300 mg every 4 weeks, and is intended for single‑agent use in the appropriate populations. Use of natalizumab is associated with risk of Progressive Multifocal Leukoencephalopathy (PML); recognized risk factors include presence of anti‑JCV antibodies, longer duration of therapy, and prior immunosuppressant exposure. Baseline and ongoing documentation (including JCV serology and appropriate objective disease assessments) are required to support appropriate, monitored use.

References, Appendices, and Supporting Materials

Selected references include pivotal and supporting trials and guideline sources relevant to natalizumab: Polman et al., AFFIRM randomized placebo‑controlled trial of natalizumab in relapsing MS (N Engl J Med. 2006); Rudick et al., SENTINEL trial of natalizumab plus interferon beta‑1a (N Engl J Med. 2006); Hemmer et al., Antelope phase 3 trial evaluating a proposed biosimilar natalizumab (JAMA Neurol. 2023); ECCO and AGA guidance on Crohn’s Disease therapeutics and medical management (J Crohn's Colitis. 2020; Gastroenterology. 2021); and other contemporary reviews of progressive MS and treatment considerations.

Appendices provided with the policy include an NQTL checklist and plan‑specific notes on utilization management, a listing of covered ICD‑10 diagnosis codes for supported indications (see Appendix 1 for the full list of G35.* and K50.* codes), and CMS‑related guidance in Appendix 2 noting that the policy is intended for non‑Medicare determinations and that applicable NCDs/LCDs/LCAs must be followed for Medicare patients.

OpenPayer

Natalizumab (Tysabri / Tyruko) prior authorization and coverage