Asset Publisher

ph-91147

print Print

Zeposia (oxanimod) Prior Authorization with Quantity Limit Program Summary

Policy Number: PH-91147

This program applies to Blue Partner, Commercial, GenPlus, NetResults A series, SourceRx and Health Insurance Marketplace formularies.            

POLICY REVIEW CYCLE                                                                                                                                                                           

Effective Date

Date of Origin 

07-01-2024            

FDA LABELED INDICATIONS AND DOSAGE

Agent(s)

FDA Indication(s)

Notes

Ref#

Zeposia®

(ozanimod)

Capsule

  • Treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults
  • Moderately to severely active ulcerative colitis (UC) in adults

1

See package insert for FDA prescribing information:  https://dailymed.nlm.nih.gov/dailymed/index.cfm

CLINICAL RATIONALE

Multiple sclerosis

Multiple sclerosis (MS) is a disorder of the central nervous system (CNS) characterized by demyelination, inflammation, and degenerative changes. Most people with MS experience relapses and remissions of neurological symptoms, particularly early in the disease, and clinical events are usually associated with areas of CNS inflammation. Gradual worsening or progression, with or without subsequent acute attacks of inflammation or radiological activity, may take place early, but usually becomes more prominent over time. While traditionally viewed as a disease solely of CNS white matter, more advanced imaging techniques have demonstrated significant early and ongoing CNS gray matter damage as well.(2)

Those diagnosed with MS may have many fluctuating and disabling symptoms (including, but not limited to, fatigue, pain, bladder and bowel issues, sexual dysfunction, movement and coordination problems, visual disturbances, and cognition and emotional changes.(18) There are currently four major types of MS: clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), primary progressive MS (PPMS), and secondary progressive MS (SPMS).(9)

Clinically isolated syndrome

CIS is a first episode of neurologic symptoms caused by inflammation and demyelination in the central nervous system. The episode, which by definition must last for at least 24 hours, is characteristic of multiple sclerosis but does not yet meet the criteria for a diagnosis of MS because people who experience a CIS may or may not go on to develop MS.(9) When caused by an acute inflammatory demyelinating event, approximately 85% of all patients subsequently develop MS. The relationship between conventional brain MRI features and the short-term risk of CIS patients developing definite MS has been assessed by several studies and allows for the diagnosis of MS based on the 2017 McDonald criteria. However, in CIS patients with initial multifocal clinical symptom presentation the abnormal MRI did not stratify the risk for clinically definite disease conversion.(17)

CIS cohort studies spanning 7 through 20 years of follow-up investigated the long-term risk of MS development and found conversions rates of 65-80% for patients with an abnormal conventional MRI and 8-20% for those with an inconspicuous baseline MRI.(17)

Relapsing remitting multiple sclerosis

RRMS is characterized by clearly defined attacks (relapses) of new or increasing neurologic symptoms. These relapses are followed by periods of partial or complete recovery. There is no or minimal disease progression during the periods between disease relapses, though individual relapses may result in severe residual disability. The course of MS varies, however, about 85-90% of individuals with MS demonstrate a relapsing pattern at onset, which transitions over time in the majority of untreated patients to a pattern of progressive worsening with few or no relapses or MRI activity.(9)

Secondary progressive multiple sclerosis

SPMS begins as RRMS, but over time the disease enters a stage of steady deterioration in function, unrelated to acute attacks. Most people with RRMS will transition to SPMS. In SPMS there is no progressive worsening of symptoms over time with no definite periods of remission.(9)

2017 McDonald Criteria for the diagnosis of Multiple Sclerosis:

Diagnostic criteria for multiple sclerosis combining clinical, imaging, and laboratory evidence have evolved over time. The increasing incorporation of paraclinical assessments, especially imaging, to supplement clinical findings has allowed earlier, more sensitive, and more specific diagnosis.(7,8)

The diagnosis of MS requires elimination of more likely diagnoses and demonstration of dissemination of lesions in the CNS in space and time.(7)

Misdiagnosis of multiple sclerosis remains an issue in clinical practice, and several factors that potentially increase this risk have been identified. Multiple sclerosis has heterogeneous clinical and imaging manifestations, which differ between patients over time. There is no single pathognomonic clinical feature or diagnostic test; diagnosis of multiple sclerosis relies on the integration of clinical, imaging, and laboratory findings. MRI abnormalities associated with other diseases and non-specific MRI findings, which are common in the general population, can be mistaken for multiple sclerosis. The increasingly strong focus on timely diagnosis to alleviate uncertainty for patients and allow initiation of disease-modifying therapies might also increase the risk of misdiagnosis.(7)

With increasing availability and use of MRI, incidental T2 hyperintensities on brain imaging are common, the subset of individuals with MRI findings that are strongly suggestive of multiple sclerosis lesions but with no neurological manifestations or other clear-cut explanation are said to have radiologically isolated syndrome. There is no consensus on whether patients with radiologically isolated syndrome will develop MS. Some practitioners argue that these patients have a high likelihood of developing MS while others argue that up to two-thirds of these patients will not receive a diagnosis of MS in 5 years.  A consensus panel decided to require clinical manifestations to make the diagnosis of MS (2017 McDonald Criteria for the diagnosis of Multiple Sclerosis).(7)

The 2017 McDonald criteria to diagnose MS is shown in the chart below.(7,8)

Clinical Presentation

Additional Data needed to make MS diagnosis

In a person with a typical attack/CIS at onset

Greater than or equal to 2 attacks and objective clinical evidence of greater than or equal to 2 lesions

OR

Greater than or equal to 2 attacks and objective clinical evidence of 1 lesion with historical evidence of prior attack involving lesion in different location

None. Dissemination in space* and dissemination in time** have been met

Greater than or equal to 2 attacks and objective clinical evidence of 1 lesion

ONE of these criteria:
Additional clinical attack implicating different CNS site
OR
Greater than or equal to 1 symptomatic or asymptomatic MS-typical T2 lesions in greater than or equal to 2 areas of CNS: periventricular, juxtacortical/cortical, infratentorial, or spinal cord

1 attack and objective clinical evidence of greater than or equal to 2 lesions

ONE of these criteria:
Additional clinical attack
OR
Simultaneous presence of both enhancing and non-enhancing symptomatic or asymptomatic MS-typical MRI lesions
OR
New T2 or enhancing MRI lesion compared to baseline scan (without regard to timing of baseline scan)
OR
CSF specific (i.e., not in serum) oligoclonal bands

1 attack and objective clinical evidence of 1 lesion

ONE of these criteria:
Additional attack implicating different CNS site
OR
Greater than or equal to 1 MS-Typical symptomatic or asymptomatic T2 lesions in greater than or equal to 2 areas of CNS: periventricular, juxtacortical/cortical, infratentorial, or spinal cord
AND
ONE of these criteria:
Additional clinical attack
OR
Simultaneous presence of both enhancing and non-enhancing symptomatic or asymptomatic MS-typical MRI lesions
OR
New T2 enhancing MRI lesion compared to baseline scan (without regard to timing of baseline scan)
OR
CSF-specific (i.e., not in serum) oligoclonal bands

* - Dissemination in space is defined as one or more T2-hyperintense lesions that are characteristic of multiple sclerosis in 2 or more of four areas of the CNS (periventricular, cortical or juxtacortical, and infratentorial brain regions, and the spinal cord) demonstrated by an additional clinical attack implicating a different CNS site or by MRI.(8)

** - Dissemination in time is defined as simultaneous presence of gadolinium-enhancing and non-enhancing lesions at any time or by a new T2-hyperintense or gadolinium-enhancing lesion on follow-up MRI, with reference to a baseline scan, irrespective of the timing of the baseline MRI. The presence of CSF-specific oligoclonal bands does not demonstrate dissemination in time per se but can substitute for the requirement for demonstration of this measure.(8)

Treatment of MS

Both the Multiple Sclerosis Coalition and the American Academy of Neurology recommend initiating treatment with a DMA FDA approved for the patient’s phenotype as soon as possible following the diagnosis of multiple sclerosis. There are several DMAs with at least 10 mechanisms of action available to people with MS. The factors affecting choice of therapy at any point in the disease course are complex and most appropriately analyzed and addressed through a shared decision-making process between the individual and the treating clinician.(2,5)

There is a subgroup of RRMS patients who have a more aggressive disease course marked by a rapid accumulation of physical and cognitive deficit, despite treatment with 1 or more DMTs. In the past, this disease phenotype was called aggressive MS; it is now called highly active MS. It is generally agreed that the severe nature of this phenotype requires different treatment decisions. There is no consensus on the definition of highly active MS or the treatment algorithm.(12) The National Institute for Health and Care Excellence (NICE) defines rapidly evolving severe RRMS as two or more disabling relapses in 1 year, and one or more gadolinium-enhancing lesions on brain MRI or a significant increase in T2 lesion load compared with a previous MRI.(6)

The Multiple Sclerosis Coalition recommends that clinicians should consider prescribing a high efficacy medication such as alemtuzumab, cladribine, fingolimod, natalizumab or ocrelizumab for newly diagnosed individuals with highly active MS. Clinicians should also consider prescribing a high efficacy medication for individuals who have breakthrough activity on another DMA regardless of the number of previously used agents.(2) The American Academy of Neurology has recommended alemtuzumab, fingolimod, and natalizumab as options for patients with MS with highly active MS. There lacks a consensus for what constitutes as highly active MS, however.(5) The National Institute for Health and Care Excellence (NICE) defines rapidly evolving severe RRMS as two or more disabling relapses in 1 year, and one or more gadolinium-enhancing lesions on brain MRI or a significant increase in T2 lesion load compared with a previous MRI.(19)

Lack of response to DMAs is hard to define, as most patients with MS are not free of all disease activity. Relapses or new MRI detected lesions may develop after initiation of a DMA and before the treatment becomes effective for patients. When determining efficacy, sufficient time for the DMA therapy to take full effect and patient adherence are important considerations. Evidence of one or more relapses, 2 or more unequivocally new MRI-detected lesions, or increased disability on examination while being treated with a DMA for a 1 year period suggests a sub-optimal response, an alternative regimen (e.g., different mechanism of action) should be considered to optimize therapeutic benefit.(5) A National MS Society consensus statement recommends changing from one disease modifying therapy to another only for medically appropriate reasons (e.g. lack of efficacy, adverse effects, or if better treatments options become available).(2)

Existing MS therapies are partly effective in halting ongoing inflammatory tissue damage and clinical progression. MS pathogenesis is complex and probably heterogeneous among patients, suggesting that combination therapy strategies that target a range of disease mechanisms might be more effective than medications used as monotherapy. Although preliminary studies have provided favorable results, however, several subsequent large, randomized, controlled trials have had negative of conflicting results. There also may be more adverse reactions associated with combination therapies due to the additive effect.(10)

In 2020 a Canadian MS working group published recommendations on optimal therapy in relapsing forms of MS. This group notes that there are few studies that have directly compared injectable and oral DMTs. A recent network meta-analysis suggested that pegylated interferon-β-1a and dimethyl fumarate have superior efficacy to other base therapies, there is insufficient data to demonstrate that one base injectable or oral DMT is superior to another. As a result, the choice of initial treatment will need to be individualized according to disease activity, severity, and comorbidities.(11)

In addition to base therapies, the working group considers 5 DMTs to be of higher efficacy which although can be used as initial therapy, they are generally reserved for patients with a poor response or tolerability with a base therapy. Patients presenting with high disease activity or aggressive/rapidly evolving MS at onset could be considered to initiate therapy with one of these more effective therapies, but the most common treatment initiation is to start on a base therapy with the view of switching within 6-12 months. The 5 agents considered to be of higher efficacy are:(11)

  • Oral agents
    • Fingolimod
    • Cladribine
  • Monoclonal antibodies
    • Natalizumab
    • Ocrelizumab
    • Alemtuzumab

The MS working group discussed the criteria for switching therapies in RRMS and recommends a change in DMT is indicated for patients who meet any of the Major criteria below:(11)

 

Minor

Major

Relapse rate

  • One relapse in first 2 years of treatment
  • Greater than or equal to 2 relapses in first year of treatment

Severity

  • Mild
  • No functional impairment (school, work, daily activities, etc.)
  • No motor/cerebellar/brain stem /sphincter involvement
  • Moderate to severe
  • Functional impairment
  • Motor/cerebellar/brain stem/sphincter involvement

Recovery

  • Full recovery at 6 months
  • No functional impairment
  • EDSS change from baseline less than or equal to 1 point at 6 months unless baseline EDSS greater than 5.5
  • Incomplete recovery
  • Functional impairment
  • If EDSS at baseline was 0 then a greater than 1.5 point change from baseline
  • If EDSS is greater than 0 but less than 5.5 at baseline then greater than 1 point change at 6 months
  • If EDSS is greater than 5.5 any change would be a major concern

MRI

  • One new lesion
  • Greater than or equal to 3 new lesions during treatment excluding spinal cord lesions
  • Greater than 1 spinal cord lesion

The workgroup does note that on-treatment relapses should only be performed once the drug has achieved a full clinical effect (typically 2-6 months after drug initiation). Relapses that occur before the maximal efficacy of the drug has been reached should be given less weight, but major criteria should take precedence regardless of timing.(11)

For patients with SPMS, the workgroup states that is generally advised to continue with the current DMT after onset of SPMS since many patients will have ongoing inflammatory disease and subclinical disease activity may worsen if treatment is withdrawn. A change in treatment may be warranted in patients with active SPMS who continue to have relapses or new MRI lesions, with the caveat that there is insufficient evidence to identify criteria for a suboptimal response in patients with SPMS.(11)

For patients with primary progressive MS, clinicians should offer ocrelizumab to patients with active disease provided the benefits outweigh the risks. Caution is recommended when considering treatment for PPMS subgroups that are less likely to benefit from treatment, such as older patients, those with long-standing stable disease, and/or significant neurological deficits, since the limited benefits may not justify the risk associated with treatment. Rituximab may be considered as an alternative therapy for PPMS in regions that permit off-label use in MS due to cost or other considerations.(11)

 

The Institute for Clinical and Economic Review (ICER) evaluated a new IV treatment, ublituximab against current FDA and accepted use DMT for adults with RRMS. Only in the case of ublituximab vs placebo/no DMT is ublituximab superior rated. The ratings are noted below.(3)

Adults with RRMS

Treatment

Comparator

Evidence Rating

Ublituximab

Natalizumab

I: Insufficient

Ofatumumab

I: Insufficient

Ocrelizumab

I: Insufficient

Rituximab

I: Insufficient

Fumarate class (dimethyl, diroximel, monomethyl

C++: Comparable or better

Fingolimod

C++: Comparable or better

Ozanimod

C++: Comparable or better

Ponesimod

C++: Comparable or better

Siponimod

I: Insufficient

Teriflunomide

B: Incremental

Placebo/no DMT

A: Superior

A: Superior - High certainty of a substantial (moderate-large) net health benefit
B: Incremental -  High certainty of a small net health benefit
C++: Comparable or better - Moderate certainty of a comparable, small, or substantial net health benefit, with which certainty of at least a comparable net health benefit
I: Insufficient - Any situation where the level of certainty in the evidence is low

ICER does note that payers should consider the following:(3)

Payors should remove barriers to access to rituximab for RMS patients who are appropriate candidates for this therapy. This includes coverage of biosimilar rituximab with little or no prior authorization given the lack of concern regarding use in appropriate patients and how inexpensive it is compared with other monoclonal antibodies of equal effectiveness

Payers should not unilaterally implement policies to switch RMS patients who are stable on their chosen DMT over to lower-cost biosimilar rituximab

Ulcerative Colitis (UC)

Ulcerative colitis (UC) is a chronic immune-mediated inflammatory condition affecting the large intestine associated with inflammation of the rectum, but that can extend to involve additional areas of the colon. The American College of Gastroenterology (ACG) recommends a treat-to-target approach and recommend therapeutic management should be guided by diagnosis (i.e., Montreal classification), assessment of disease activity (i.e., mild, moderate, and severe), and disease prognosis. The ACG treatment recommendations are further broken down into induction therapies and maintenance of remission. The 2019 ACG treatment guidelines recommend the following for therapeutic management of UC:(14)

Induction of remission:

  • Mildly active disease:
    • Rectal 5-ASA at a dose of 1 g/day with or without oral 5-ASA at a dose of at least 2 g/day for left-sided UC
    • Rectal 5-ASA at a dose of 1 g/day for ulcerative proctitis
    • Oral 5-ASA at a dose of at least 2 g/day for extensive UC
    • Add oral budesonide multi-matrix (MMX) 9 mg/day for patients that are intolerant or non-responsive to oral and/or rectal and oral 5-ASA at appropriate doses
  • Moderately active disease:
    • Oral budesonide multi-matrix (MMX) 9 mg/day for induction of remission
  • Moderately to severely active disease:
    • Oral systemic corticosteroids, TNF inhibitors (i.e., adalimumab, golimumab, or infliximab), tofacitinib, or vedolizumab to induce remission
    • Combination of infliximab with thiopurine therapy when using infliximab for induction
    • Switch to tofacitinib or vedolizumab for induction in patients that have failed TNF inhibitors
    • Patients with initial response to TNF inhibitors that lose response should have antibody levels and serum drug levels tested to assess reason for loss of response. If serum levels are adequate, use of another TNF inhibitor is not likely to be of benefit. 

 Maintenance of remission:

  • Previously mildly active disease:
    • Rectal 5-ASA at a dose of 1 g/day in patients with ulcerative proctitis
    • Oral 5-ASA at a dose of at least 2 g/day in patients with left-sided or extensive UC
  • Previously moderately to severely active disease:
    • Thiopurines in patients that achieved remission due to corticosteroid induction
    • Continue TNF inhibitors (i.e., adalimumab, golimumab, or infliximab) for remission due to TNF induction
    • Continue vedolizumab for remission due to vedolizumab induction
    • Continue tofacitinib for remission due to tofacitinib induction

The American Gastroenterology Association (AGA) published recommendations for the management of mild to moderate UC:(15)

  • Use either standard-dose mesalamine (2-3 g/day) or diazo-bonded 5-ASA for patients with extensive UC for induction of remission and maintenance of remission
  • May add rectal mesalamine to oral 5-ASA in patients with extensive or left-sided UC for induction of remission and maintenance of remission
  • Use high dose mesalamine (greater than 3 g/day) with rectal mesalamine in patients with suboptimal response to standard-dose mesalamine, diazo-bonded 5-ASA, or with moderate disease activity for induction of remission and maintenance of remission
  • Add either oral prednisone or budesonide MMX in patients that are refractory to optimized oral and rectal 5-ASA regardless of disease extent

The American Gastroenterology Association (AGA) published recommendations for the management of moderate to severe UC:(16)

  • Standard of care is to continue agents initiated for induction therapy as maintenance therapy, if they are effective (excluding corticosteroids and cyclosporine)
  • Adult outpatients with moderate to severe UC:
    • Infliximab, adalimumab, golimumab, vedolizumab, tofacitinib or ustekinumab are strongly recommended over no treatment
    • Biologic naïve patients:
      • infliximab or vedolizumab are conditionally recommended over adalimumab for induction of remission
      • Recommend tofacitinib only be used in the setting of a clinical or registry study
    • Previous exposure to infliximab, particularly those with primary non-response, ustekinumab or tofacitinib are conditionally recommended over vedolizumab or adalimumab for induction of remission
    • Conditionally recommend against use of thiopurine monotherapy for induction, but may be used for maintenance of remission over no treatment

Safety

Zeposia (ozanimod) is contraindicated in:(1)

  • In patients who in, the last 6 months, experienced myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization, or Class III or IV heart failure
  • Presence of Mobitz type II second-degree or third degree atrioventricular (AV) block, sick sinus syndrome, or sino-atrial block, unless the patient has a functioning pacemaker
  • Severe untreated sleep apnea
  • Concomitant use with a monoamine oxidase inhibitor

REFERENCES                                                                                                                                                                           

Number

Reference

1

Zeposia prescribing information. Celgene Corporation. August 2023.

2

Multiple Sclerosis Coalition. The Use of Disease Modifying Therapies in Multiple Sclerosis: Principals and Current Evidence. Updated June 2019. National Multiple Sclerosis Society. Available at: https://www.nationalmssociety.org/NationalMSSociety/media/MSNationalFiles/Brochures/DMT_Consensus_MS_Coalition.pdf.

3

Institute for Clinical and Economic Review (ICER). Oral and monoclonal Antibody Treatments for Relapsing Forms of Multiple Sclerosis: Effectiveness and Value. February 21,2023.

4

Rae-Grant, Alexander, MD, et al. Practice Guideline Recommendations Summary: Disease-Modifying Therapies for Adults with Multiple Sclerosis. Neurology. 2018;90:777-788.

5

Corboy, John R, MD, et al. Comment on 2018 American Academy of Neurology Guidelines on Disease-Modifying Therapies in MS. Neurology. 2018;90:1106-1112.

6

Reference no longer used

7

Thompson AJ, Banwell BL, Barkhof F, et al. Diagnosis of multiple sclerosis:2017 revisions of the McDonald criteria. Lancet Neurol 2018; 17:162-73.

8

National Multiple Sclerosis Society 2017 McDonald MS Diagnostic Criteria. Available at: https://www.nationalmssociety.org/For-Professionals/Clinical-Care/Diagnosing-MS/Diagnosing-Criteria.

9

MS international federation. Types of MS. Last updated 12th March 2022. Accessed at Types of MS | Multiple Sclerosis (msif.org)

10

Conway D, Cohen JA. Combination therapy in multiple sclerosis. Lancet Neurol 2010 Mar;9(3):299-308.

11

Freedman MS, Devonshire V, Duquette P, et al. Treatment Optimization in Multiple Sclerosis: Canadian MS Working Group Recommendations. The Can J Neurol Sci. 2020;47:437-455.

12

Reference no longer used

13

Reference not used

14

Rubin, D. T., MD, FACG, Ananthakrishnan, A. N., M.D., M.PH., Siegel, C. A., M.D., M.S., Sauer, B. G., M.D., M.Sc., FACG, & Long, M.D., M.PH., FACG. ACG Clinical Guideline: Ulcerative Colitis in Adults. The American Journal of Gastroenterology. 2019; 114:384-413. Retrieved March 8, 2019, from http://s3.gi.org/physicians/guidelines/UlcerativeColitis.pdf

15

Ko, Cynthia W., Crockett, Seth, et al. AGA Clinical Practice Guidelines on the Management of Mild-to-Moderate Ulcerative Colitis. Gastroenterology. 2019; 156(3):748-764. Retrieved March 8, 2019, from https://www.gastrojournal.org/article/S0016-5085(18)35407-6/pdf.  

16

Feuerstein, Joseph D. et al. AGA Clinical Practice Guidelines on the Management of Moderate to Severe Ulcerative Colitis. Gastroenterology, Volume 0, Issue 0.

17

Kitzler HH, Wahl H, Eisele JC, et al. Multi-component relaxation in clinically isolated syndrome; Lesion myelination may predict multiple sclerosis conversion. NeuroImage:Clinical 20 (2018)61-70.

18

MS international federation. About MS - Symptoms. Accessed at  MS Symptoms | Multiple Sclerosis (msif.org)

19

National Institute for Health and Care Excellence. NICE Guidance  - Conditions and diseases - Neurological conditions -Multiple sclerosis. Ofatumumab for treating relapsing multiple sclerosis. Technology appraisal guidance [TA699] Published:19 May 2021. Accessed at 3 Committee discussion | Ofatumumab for treating relapsing multiple sclerosis | Guidance | NICE

POLICY AGENT SUMMARY PRIOR AUTHORIZATION

Target Brand Agent(s)

Target Generic Agent(s)

Strength

Targeted MSC

Available MSC

Final Age Limit

Preferred Status

Zeposia ; Zeposia 7-day starter pac ; Zeposia starter kit

ozanimod cap pack  ; ozanimod hcl cap

0.23MG & 0.46MG & 0.92MG ; 0.23MG &0.46MG 0.92MG(21) ; 0.92 MG ; 4 x 0.23MG & 3 x 0.46MG

M ; N ; O ; Y

N

POLICY AGENT SUMMARY QUANTITY LIMIT

Target Brand Agent Name(s)

Target Generic Agent Name(s)

Strength

QL Amount

Dose Form

Day Supply

Duration

Addtl QL Info

Allowed Exceptions

Targeted NDCs When Exclusions Exist

Zeposia

ozanimod hcl cap

0.92 MG

30

Capsules

30

DAYS

Zeposia 7-day starter pac

Ozanimod Cap Pack 4 x 0.23 MG & 3 x 0.46 MG

4 x 0.23MG & 3 x 0.46MG

7

Capsules

180

DAYS

Zeposia starter kit

ozanimod cap pack

0.23MG &0.46MG 0.92MG(21)

28

Capsules

180

DAYS

Zeposia starter kit

Ozanimod Cap Pack 4 x 0.23 MG & 3 x 0.46 MG & 30 x 0.92 MG

0.23MG & 0.46MG & 0.92MG

37

Capsules

180

DAYS

CLIENT SUMMARY – PRIOR AUTHORIZATION

Target Brand Agent Name(s)

Target Generic Agent Name(s)

Strength

Client Formulary

Zeposia ; Zeposia 7-day starter pac ; Zeposia starter kit

ozanimod cap pack  ; ozanimod hcl cap

0.23MG & 0.46MG & 0.92MG ; 0.23MG &0.46MG 0.92MG(21) ; 0.92 MG ; 4 x 0.23MG & 3 x 0.46MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

CLIENT SUMMARY – QUANTITY LIMITS

Target Brand Agent Name(s)

Target Generic Agent Name(s)

Strength

Client Formulary

Zeposia

ozanimod hcl cap

0.92 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Zeposia 7-day starter pac

Ozanimod Cap Pack 4 x 0.23 MG & 3 x 0.46 MG

4 x 0.23MG & 3 x 0.46MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Zeposia starter kit

ozanimod cap pack

0.23MG &0.46MG 0.92MG(21)

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Zeposia starter kit

Ozanimod Cap Pack 4 x 0.23 MG & 3 x 0.46 MG & 30 x 0.92 MG

0.23MG & 0.46MG & 0.92MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

PRIOR AUTHORIZATION CLINICAL CRITERIA FOR APPROVAL

Module

Clinical Criteria for Approval

Zeposia PA with MS Step

Initial Evaluation

Target Agent(s) will be approved when ONE of the following is met:

  1. The requested agent is eligible for continuation of therapy AND ONE of following:

Agents Eligible for Continuation of Therapy

Zeposia (ozanimod)

    1. The patient has been treated with the requested agent within the past 90 days OR
    2. The prescriber states the patient has been treated with the requested agent within the past 90 days AND is at risk if therapy is changed OR
  1. The patient has a diagnosis of multiple sclerosis (MS) AND ONE of the following:
    1. ONE of the following:
      1. The patient has highly active MS disease activity AND BOTH of the following:
        1. The patient has greater than or equal to 2 relapses in the previous year AND
        2. ONE of the following:
          1. The patient has greater than or equal to 1 gadolinium enhancing lesion on MRI OR
          2. The patient has significant increase in T2 lesion load compared with a previous MRI OR
      2. The patient has been treated with at least 3 MS agents from different drug classes (see MS disease modifying agents drug class table)  OR
      3. The patient’s medication history incudes use of ONE preferred generic MS agent*  OR
      4. The patient has an intolerance (defined as an intolerance to the drug or its excipients, not to the route of administration) or hypersensitivity to ONE preferred generic MS agent* OR
      5. The patient has an FDA labeled contraindication to ALL preferred generic MS agents AND
    2. The patient will NOT be using the requested agent in combination with another MS disease modifying agent (DMA) (Please refer to "Multiple Sclerosis Disease Modifying Agents" contraindicated use table) OR  
  2. The patient has a diagnosis of moderately to severely active ulcerative colitis (UC) AND ALL of the following:
    1. ONE of the following:
      1. The patient has tried and had an inadequate response to ONE conventional agent (i.e., 6-mercaptopurine, azathioprine, balsalazide, corticosteroids, cyclosporine, mesalamine, sulfasalazine) used in the treatment of UC for at least 3-months OR
      2. The patient has severely active ulcerative colitis OR
      3. The patient has an intolerance or hypersensitivity to ONE of the conventional agents used in the treatment of UC OR
      4. The patient has an FDA labeled contraindication to ALL of the conventional agents used in the treatment of UC OR
      5. The patient’s medication history indicates use of another biologic immunomodulator agent that is FDA labeled or supported in compendia for the treatment of UC AND
    2. ONE of the following:
      1. The patient has tried and had an inadequate response to TWO Step 1a and/or Step 1b immunomodulatory agents (see Immunomodulatory Agent Step table) OR
      2. The patient has an intolerance (defined as an intolerance to the drug or its excipients, not to the route of administration) or hypersensitivity to at least TWO Step 1a and/or Step 1b immunomodulatory agents OR
      3. The patient has an FDA labeled contraindication to ALL Step 1a AND Step1b immunomodulatory agents AND
    3. The patient will NOT be using the requested agent in combination with another immunomodulatory agent (e.g., TNF inhibitors, JAK inhibitors, IL-4 inhibitors) (Please refer to "Immunomodulatory Agents NOT to be used Concomitantly" table) AND
    4. If the patient has an FDA labeled indication, then ONE of the following:
      1. The patient’s age is within FDA labeling for the requested indication for the requested agent OR
      2. There is support for using the requested agent for the patient’s age for the requested indication AND   
    5. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., gastroenterologist), or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
    6. The patient does NOT have any FDA labeled contraindications to the requested agent

Compendia Allowed: AHFS, or DrugDex 1 or 2a level of evidence

Length of Approval: 12 months. NOTE: The starter dose can be approved for the FDA labeled starting dose and the maintenance dose can be approved for the remainder of 12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

 

Renewal Evaluation

Target Agent(s) will be approved when BOTH of the following are met:

  1. The patient has been previously approved for the requested agent through the plan’s Prior Authorization process (Note: patients not previously approved for the requested agent will require initial evaluation review) AND
  2. ONE of the following:
    1. The patient has a diagnosis of multiple sclerosis (MS) AND BOTH of the following:
      1. ONE of the following:
        1. The requested agent is eligible for continuation of therapy AND ONE of following:

Agents Eligible for Continuation of Therapy

Zeposia (ozanimod)

          1. The patient has been treated with the requested agent within the past 90 days OR
          2. The prescriber states the patient has been treated with the requested agent within the past 90 days AND is at risk if therapy is changed OR
        1. The patient has highly active MS disease activity AND BOTH of the following:
          1. The patient has greater than or equal to 2 relapses in the previous year AND
          2. ONE of the following:
            1. The patient has greater than or equal to 1 gadolinium enhancing lesion on MRI OR
            2. The patient has significant increase in T2 lesion load compared with a previous MRI OR
        2. The patient has been treated with at least 3 MS agents from different drug classes (see MS disease modifying agents drug class table) OR
        3. The patient’s medication history incudes use of ONE preferred generic MS agent* OR
        4. The patient has an intolerance (defined as an intolerance to the drug or its excipients, not to the route of administration) or hypersensitivity to ONE preferred generic MS agent* OR
        5. The patient has an FDA labeled contraindication to ALL preferred generic MS agents* AND
      1. The patient will not be using the requested agent in combination with another MS disease modifying agent (DMA) (Please refer to "Multiple Sclerosis Disease Modifying Agents" contraindicated use table) OR
    1. The patient has a diagnosis of ulcerative colitis AND ALL of the following:
      1. The patient has had clinical benefit with the requested agent AND
      2. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., gastroenterologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
      3. The patient does NOT have any FDA labeled contraindications to the requested agent AND
      4. The patient will NOT be using the requested agent in combination with another immunomodulatory agent (see "Immunomodulatory Agents NOT to be used Concomitantly" table)

Length of Approval:   12 months 

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

 

* Preferred and Non-preferred MS agents

Preferred generic agents
dimethyl fumarate
fingolimod
glatiramer
teriflunomide

Preferred brand agents
Aubagio (teriflunomide)**
Avonex (interferon b-1a)
Betaseron (interferon b-1b)
Kesimpta (ofatumumab)
Mavenclad (cladribine)
Mayzent (siponimod)
Plegridy (peginterferon b-1a)
Rebif (interferon b-1a)
Zeposia (ozanimod)

Non-Preferred Agents
Bafiertam (monomethyl fumarate)
Copaxone (glatiramer)**
Extavia (interferon b-1b)
Gilenya (fingolimod)**
Glatopa (glatiramer)
Ponvory (ponesimod)
Tascenso ODT (fingolimod)
Tecfidera (dimethyl fumarate)**
Vumerity (diroximel fumarate)

** -generic available

Immunomodulatory Agent Step table

Formulary

Step 1a

Step 1b (Directed to ONE TNF inhibitor) NOTE Please see Step 1a for preferred TNF inhibitors

Step 2 (Directed to ONE Step 1 agent)

Step 3a (Directed to TWO Step 1 agents)

Step 3b (Directed to TWO agents from Step 1a and/or Step 1b)

Step 3c  (Directed to THREE step 1 agents)

Blue Partner, Commercial, GenPlus, SourceRx and Health Insurance Marketplace

SQ:
Hadlima, Humira,
Stelara

Oral:
Rinvoq, Xeljanz/Xeljanz XR

SQ:
Simponi
(Hadlima or Humira is required Step 1 agent)

N/A

SQ: Entyvio

Oral: Zeposia (Hadlima, Humira, Rinvoq, Stelara, OR Xeljanz/Xeljanz XR are required Step agents)

SQ: Abrilada*, Amjevita*, Cyltezo*, Hulio*, Hyrimoz*, Idacio*, Omvoh, Yuflyma*, Yusimry*, Zymfentra

Oral:
Velsipity

NetResults A series

SQ:
Cyltezo, Humira,
Stelara

Oral:
Rinvoq, Xeljanz/Xeljanz XR

SQ:
Simponi
(Cyltezo or Humira is required Step 1 agent)

N/A

SQ: Entyvio

Oral: Zeposia (Cyltezo, Humira, Rinvoq, Stelara, OR Xeljanz/Xeljanz XR are required Step 1 agents)

SQ: Abrilada**, Amjevita**, Hadlima**, Hulio**, Hyrimoz**, Idacio**, Omvoh, Yuflyma**, Yusimry**, Zymfentra

Oral:
Velsipity

* Hadlima and Humira are required Step 1 agents

** Cyltezo and Humira are required Step 1 agents

QUANTITY LIMIT CLINICAL CRITERIA FOR APPROVAL

Module

Clinical Criteria for Approval

Zeposia PA with MS Step

Quantity Limit for the Target Agent(s) will be approved when ONE of the following is met:

  1. The requested quantity (dose) does NOT exceed the program quantity limit OR
  2. ALL of the following:
    1. The requested quantity (dose) exceeds the program quantity limit AND
    2. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND
    3. The requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does not exceed the program quantity limit OR
  3. ALL of the following:
    1. The requested quantity (dose) exceeds the program quantity limit AND
    2. The requested quantity (dose) exceeds the maximum FDA labeled dose for the requested indication AND
    3. There is support for therapy with a higher dose for the requested indication

Length of Approval: up to 12 months. NOTE: The starter dose can be approved for the FDA labeled starting dose and the maintenance dose can be approved for the remainder of 12 months.  

CLASS AGENTS

Class

Class Drug Agents

Class Ia antiarrhythmics

Class Ia antiarrhythmics

NORPACE*Disopyramide Phosphate Cap

Class Ia antiarrhythmics

PROCAINAMIDE*Procainamide HCl Inj

Class Ia antiarrhythmics

QUINIDINE*Quinidine

Class III antiarrhythmics

Class III antiarrhythmics

 Cordarone, Pacerone (amiodarone)

Class III antiarrhythmics

BETAPACE*Sotalol HCl Tab

Class III antiarrhythmics

CORVERT*Ibutilide Fumarate Inj

Class III antiarrhythmics

MULTAQ*Dronedarone HCl Tab

Class III antiarrhythmics

TIKOSYN*Dofetilide Cap

MS Disease Modifying Agents drug class: CD20 monoclonal antibody

MS Disease Modifying Agents drug class: CD20 monoclonal antibody

BRIUMVI*ublituximab-xiiy soln for iv infusion

MS Disease Modifying Agents drug classes: CD20 monoclonal antibody

MS Disease Modifying Agents drug classes: CD20 monoclonal antibody

KESIMPTA*Ofatumumab Soln Auto-Injector

MS Disease Modifying Agents drug classes: CD20 monoclonal antibody

OCREVUS*Ocrelizumab Soln For IV Infusion

MS Disease Modifying Agents drug classes: CD52 monoclonal antibody

MS Disease Modifying Agents drug classes: CD52 monoclonal antibody

LEMTRADA*Alemtuzumab IV Inj

MS Disease Modifying Agents drug classes: Fumarates

MS Disease Modifying Agents drug classes: Fumarates

BAFIERTAM*Monomethyl Fumarate Capsule Delayed Release

MS Disease Modifying Agents drug classes: Fumarates

TECFIDERA*Dimethyl Fumarate Capsule Delayed Release

MS Disease Modifying Agents drug classes: Fumarates

VUMERITY*Diroximel Fumarate Capsule Delayed Release

MS Disease Modifying Agents drug classes: Glatiramer

MS Disease Modifying Agents drug classes: Glatiramer

COPAXONE*Glatiramer Acetate Soln Prefilled Syringe

MS Disease Modifying Agents drug classes: Glatiramer

GLATOPA*Glatiramer Acetate Soln Prefilled Syringe

MS Disease Modifying Agents drug classes: IgG4k monoclonal antibody

MS Disease Modifying Agents drug classes: IgG4k monoclonal antibody

TYSABRI*Natalizumab for IV Inj Conc

MS Disease Modifying Agents drug classes: Interferons

MS Disease Modifying Agents drug classes: Interferons

AVONEX*Interferon beta-1a injection

MS Disease Modifying Agents drug classes: Interferons

BETASERON*Interferon beta-1b injection

MS Disease Modifying Agents drug classes: Interferons

EXTAVIA*Interferon beta-1b injection

MS Disease Modifying Agents drug classes: Interferons

PLEGRIDY*Peginterferon beta-1a injection

MS Disease Modifying Agents drug classes: Interferons

REBIF*Interferon beta-1a injection

MS Disease Modifying Agents drug classes: Purine antimetabolite

MS Disease Modifying Agents drug classes: Purine antimetabolite

MAVENCLAD*Cladribine Tab Therapy Pack

MS Disease Modifying Agents drug classes: Pyrimidine synthesis inhibitor

MS Disease Modifying Agents drug classes: Pyrimidine synthesis inhibitor

AUBAGIO*Teriflunomide Tab

MS Disease Modifying Agents drug classes: Sphingosine 1-phosphate (SIP) receptor modulator

MS Disease Modifying Agents drug classes: Sphingosine 1-phosphate (SIP) receptor modulator

GILENYA*Fingolimod HCl Cap

MS Disease Modifying Agents drug classes: Sphingosine 1-phosphate (SIP) receptor modulator

MAYZENT*Siponimod Fumarate Tab

MS Disease Modifying Agents drug classes: Sphingosine 1-phosphate (SIP) receptor modulator

PONVORY*Ponesimod Tab

MS Disease Modifying Agents drug classes: Sphingosine 1-phosphate (SIP) receptor modulator

TASCENSO*fingolimod lauryl sulfate tablet disintegrating

MS Disease Modifying Agents drug classes: Sphingosine 1-phosphate (SIP) receptor modulator

ZEPOSIA*Ozanimod capsule

CONTRAINDICATION AGENTS

Contraindicated as Concomitant Therapy

MS Disease Modifying Agents

Aubagio (teriflunomide)

Avonex (interferon b-1a)

Bafiertam (monomethyl fumarate)

Betaseron (interferon b-1b)

Briumvi (ublituximab-xiiy)

Copaxone (glatiramer)

dimethyl fumarate

Extavia (interferon b-1b)

fingolimod

Gilenya (fingolimod)

Glatopa (glatiramer)

glatiramer

Kesimpta (ofatumumab)

Mavenclad (cladribine)

Mayzent (siponimod)

Plegridy (peginterferon b-1a)

Ponvory (ponesimod)

Rebif (interferon b-1a)

Tascenso ODT (fingolimod)

Tecfidera (dimethyl fumarate)

Vumerity (diroximel fumarate)

Zeposia (ozanimod)

 

Immunomodulatory Agents NOT to be used concomitantly

Abrilada (adalimumab-afzb)

Actemra (tocilizumab)

Adalimumab

Adbry (tralokinumab-ldrm)

Amjevita (adalimumab-atto)

Arcalyst (rilonacept)

Avsola (infliximab-axxq)

Benlysta (belimumab)

Bimzelx (bimekizumab-bkzx)

Cibinqo (abrocitinib)

Cimzia (certolizumab)

Cinqair (reslizumab)

Cosentyx (secukinumab)

Cyltezo (adalimumab-adbm)

Dupixent (dupilumab)

Enbrel (etanercept)

Entyvio (vedolizumab)

Fasenra (benralizumab)

Hadlima (adalimumab-bwwd)

Hulio (adalimumab-fkjp)

Humira (adalimumab)

Hyrimoz (adalimumab-adaz)

Idacio (adalimumab-aacf)

Ilaris (canakinumab)

Ilumya (tildrakizumab-asmn)

Inflectra (infliximab-dyyb)

Infliximab

Kevzara (sarilumab)

Kineret (anakinra)

Litfulo (ritlecitinib)

Nucala (mepolizumab)

Olumiant (baricitinib)

Omvoh (mirikizumab-mrkz)

Opzelura (ruxolitinib)

Orencia (abatacept)

Otezla (apremilast)

Remicade (infliximab)

Renflexis (infliximab-abda)

Riabni (rituximab-arrx)

Rinvoq (upadacitinib)

Rituxan (rituximab)

Rituxan Hycela (rituximab/hyaluronidase human)

Ruxience (rituximab-pvvr)

Siliq (brodalumab)

Simponi (golimumab)

Simponi ARIA (golimumab)

Skyrizi (risankizumab-rzaa)

Sotyktu (deucravacitinib) 

Stelara (ustekinumab)

Taltz (ixekizumab)

Tezspire (tezepelumab-ekko)

Tremfya (guselkumab)

Truxima (rituximab-abbs)

Tysabri (natalizumab)

Velsipity (etrasimod)

Wezlana (ustekinumab-auub)

Xeljanz (tofacitinib)

Xeljanz XR (tofacitinib extended release)

Xolair (omalizumab)

Yuflyma (adalimumab-aaty)

Yusimry (adalimumab-aqvh)

Zeposia (ozanimod)

Zymfentra (infliximab-dyyb)

This pharmacy policy is not an authorization, certification, explanation of benefits or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All pharmacy policies are based on (i) information in FDA approved package inserts (and black box warning, alerts, or other information disseminated by the FDA as applicable); (ii) research of current medical and pharmacy literature; and/or (iii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

The purpose of Blue Cross and Blue Shield of Alabama’s pharmacy policies are to provide a guide to coverage. Pharmacy policies are not intended to dictate to physicians how to practice medicine. Physicians should exercise their medical judgment in providing the care they feel is most appropriate for their patients.  

Neither this policy, nor the successful adjudication of a pharmacy claim, is guarantee of payment.

 

 

 

Commercial _ PS _ Zeposia_(ozanimod)_PAQL _ProgSum_ 07-01-2024