Centene Pombiliti+Opfolda Coverage Update

Coverage Criteria

inv-01: Initial Therapy — Pompe Disease

Covered when ALL of the following are met for Initial Approval for Pompe Disease

Pompe Initial Criteria: 1. Diagnosis of late-onset Pompe disease confirmed by one of the following: (a) enzyme assay confirming low GAA activity; (b) DNA testing; or (c) increased lysosomal glycogen; 2. Age ≥ 18 years; 3. Member weighs ≥ 40 kg; 4. Pombiliti and Opfolda are prescribed together; 5. Pombiliti and Opfolda are not prescribed concurrently with Lumizyme or Nexviazyme; 6. Dose does not exceed weight-based limits: (a) Members weighing ≥ 50 kg: Pombiliti 20 mg/kg IV every other week with Opfolda 260 mg (4 capsules) every other week; (b) Members weighing ≥ 40 kg to < 50 kg: Pombiliti 20 mg/kg IV every other week with Opfolda 195 mg (3 capsules) every other week.

Initial approval durations vary by line of business.

inv-02: Continuation Therapy — Pompe Disease

Covered when ALL of the following are met for Continued Therapy for Pompe Disease

Pompe Continued Therapy: 1. Member meets one of the following: (a) currently receiving medication via Centene benefit or previously met initial approval criteria; or (b) currently receiving medication and enrolled in a state/product with continuity of care regulations; 2. Member is responding positively to therapy as evidenced by improvement in the individual's Pompe disease manifestation profile; 3. Pombiliti and Opfolda are prescribed together; 4. Pombiliti and Opfolda are not prescribed concurrently with Lumizyme or Nexviazyme; 5. If request is for a dose increase, the new dose does not exceed weight-based limits: (a) ≥ 50 kg: Pombiliti 20 mg/kg IV every other week with Opfolda 260 mg every other week; (b) 40 to <50 kg: Pombiliti 20 mg/kg IV every other week with Opfolda 195 mg every other week.

Approval duration: Medicaid/HIM 12 months; Commercial 6 months or to renewal date.

inv-03: Opfolda — Niemann-Pick Disease Type C (off-label)

Covered when ALL of the following are met for Opfolda use in Niemann-Pick Disease Type C (off-label)

NPC Initial/Continued Therapy: 1. Diagnosis of Niemann-Pick disease type C (NPC) confirmed by one of the following: (a) genetic analysis indicating mutation in both alleles of NPC1 or NPC2; or (b) genetic analysis indicating mutation in one allele of NPC1 or NPC2 plus (i) positive filipin staining or (ii) positive biomarker (e.g., oxysterol, lyso-sphingolipid, bile acid); 2. Request is for Opfolda without Pombiliti; 3. Prescribed by or in consultation with a geneticist, neurologist, endocrinologist, or metabolic disease specialist; 4. Member presents with at least one neurological sign or symptom of NPC; 5. Dose does not exceed 585 mg (9 capsules) per day.585 mg/day

Approval duration: 12 months.

inv-04: Initial and Continued Therapy (summary)

Covered when ALL of the following are met (dosing and concomitant prescribing requirements reflected):

Dosing: Pombiliti administered 20 mg/kg IV every other week; Opfolda administered orally every other week with weight-based dose: ≥50 kg: Opfolda 260 mg (4 capsules) per dose; 40 to <50 kg: Opfolda 195 mg (3 capsules) per dose.weight-based

Initial and continued therapy require both agents to be prescribed together per FDA labeling and policy updates.

Authorization duration: Initial authorization duration updated to 12 months for Medicaid/HIM as of 1Q 2026 review.12 months

Referenced in annual review summary.

Non‑FDA approved indications that are not specifically addressed in this policy are not authorized unless the provider supplies sufficient documentation of efficacy and safety in accordance with the applicable off‑label use policies: CP.CPA.09 (commercial), HIM.PA.154 (Health Insurance Marketplace), or CP.PMN.53 (Medicaid), or unless coverage is supported by the member’s evidence of coverage.

For continued therapy the policy explicitly excludes concurrent use of Pombiliti + Opfolda with other recombinant acid α‑glucosidase products. Concurrent administration with Lumizyme® or Nexviazyme® is not allowed and such combinations are not authorized under the continued therapy criteria.

Requests that fail to meet any of the policy’s stated diagnostic, age, weight, concomitant therapy, or dosing requirements are not authorized. Examples include lack of confirmed late‑onset Pompe diagnosis, age under 18 years, weight under 40 kg, failure to prescribe both Pombiliti and Opfolda together when required, concurrent use with excluded enzyme products, or dosing that exceeds the specified weight‑based limits.

The policy does not list specific conditions labeled as “not medically necessary” in this excerpt. Importantly, coding information included in the clinical policy is provided for informational purposes only; inclusion or exclusion of procedure or billing codes does not guarantee coverage and providers should reference current professional coding guidance prior to claim submission.

Initial Therapy Criteria

inv-27: Initial Therapy — Initial therapy requirements for Pompe disease

Initial therapy requirements for Pompe disease

Initial drug nodes: 1. Diagnosis of late-onset Pompe disease confirmed by enzyme assay (low GAA activity) OR DNA testing OR increased lysosomal glycogen; 2. Age ≥ 18 years; 3. Member weighs ≥ 40 kg; 4. Pombiliti and Opfolda must be prescribed together; 5. Concurrent prescription with Lumizyme or Nexviazyme is not allowed; 6. Dosing within specified weight-based limits: (a) ≥50 kg: Pombiliti 20 mg/kg IV every other week + Opfolda 260 mg every other week; (b) 40 to <50 kg: Pombiliti 20 mg/kg IV every other week + Opfolda 195 mg every other week.

inv-28: Initial Therapy — NPC (Opfolda)

Initial therapy requirements for Niemann-Pick Disease Type C (Opfolda alone)

NPC initial nodes: 1. Diagnosis of NPC confirmed by genetic analysis: (a) mutation in both alleles of NPC1 or NPC2; or (b) mutation in one allele plus positive filipin staining or positive biomarker; 2. Request is for Opfolda without Pombiliti; 3. Prescribed by or in consultation with an appropriate specialist (geneticist, neurologist, endocrinologist, or metabolic disease specialist); 4. Member has at least one neurological sign or symptom of NPC; 5. Dose does not exceed 585 mg (9 capsules) per day.

Continuation / Continued Therapy Criteria

inv-30: Continuation Therapy — Criteria for continued coverage

Criteria for continued coverage

Continuation nodes: 1. Member currently receiving medication via Centene benefit or previously met initial approval criteria OR member is currently receiving medication and continuity of care applies; 2. Member is responding positively to therapy as evidenced by improvement in Pompe disease manifestations (see policy appendices for examples); 3. Pombiliti and Opfolda are prescribed together; 4. Pombiliti and Opfolda are not prescribed concurrently with Lumizyme or Nexviazyme; 5. If dose increase requested, new dose must not exceed weight-based limits: (a) ≥50 kg: Pombiliti 20 mg/kg IV every other week + Opfolda 260 mg every other week; (b) 40 to <50 kg: Pombiliti 20 mg/kg IV every other week + Opfolda 195 mg every other week.

inv-31: Continued Therapy — Continued therapy requires that both Pombiliti and Opfolda be prescribed together; exclusion of concurrent enzyme products applies.

Continued therapy requires that both Pombiliti and Opfolda be prescribed together; exclusion of concurrent enzyme products applies.

Concurrent prescribing: 1. Pombiliti and Opfolda must be prescribed together for continued therapy; 2. Concurrent use of Pombiliti and Opfolda with Lumizyme or Nexviazyme is excluded and may trigger denial.

Provider Actions & Documentation

Prior Authorization

Pompe disease — Prior Authorization Required

Prior authorization is required for treatment of Pompe disease. Approval is contingent on documentation confirming late-onset Pompe disease (enzyme assay showing low GAA activity, DNA testing, or increased lysosomal glycogen), age ≥ 18 years, weight ≥ 40 kg, and that Pombiliti and Opfolda are prescribed together. Dosing limits apply by weight. Pombiliti and Opfolda must not be prescribed concurrently with Lumizyme or Nexviazyme.

Initial and continued therapy require Pombiliti + Opfolda prescribed together
Diagnosis confirmation: enzyme assay OR DNA testing OR increased lysosomal glycogen
Age requirement: ≥ 18 years
Weight requirement: ≥ 40 kg
Concurrent use with Lumizyme or Nexviazyme is excluded
Dosing limits by weight: ≥50 kg: Pombiliti 20 mg/kg + Opfolda 260 mg q2wk; 40–<50 kg: Pombiliti 20 mg/kg + Opfolda 195 mg q2wk

Prior Authorization

Niemann-Pick Disease Type C (off-label) — Prior Authorization Required

Coding

Policy HCPCS/J codes (added and removed historically)mixed

G0138	Intravenous infusion of cipaglucosidase alfa-atga, including provider/supplier acquisition and clinical supervision of oral administration of miglustat in preparation of receipt of cipaglucosidase alfa-atga.
J1202	Miglustat, oral, 65 mg.
J1203	Injection, cipaglucosidase alfa-atga, 5 mg.
C9399	Previously referenced HCPCS code removed from policy history.
J3590	Previously referenced HCPCS code removed from policy history.

Weight threshold for treatment

Minimum member weightMembers weighing ≥ 40 kg

Higher-weight dosing tierMembers weighing ≥ 50 kg — dosing uses Pombiliti 20 mg/kg + Opfolda 260 mg every other week

Lower-weight dosing tierMembers weighing 40 to <50 kg — dosing uses Pombiliti 20 mg/kg + Opfolda 195 mg every other week

Weight-based dosing threshold

Primary weight breakpoint≥ 50 kg — Pombiliti 20 mg/kg IV every other week with Opfolda 260 mg (4 capsules) PO every other week

Secondary weight range40 to <50 kg — Pombiliti 20 mg/kg IV every other week with Opfolda 195 mg (3 capsules) PO every other week

Step Therapy

Step	Requirement	Failure criteria / notes
1	Pombiliti (cipaglucosidase alfa-atga) + Opfolda (miglustat) prescribed together for adult members weighing ≥ 40 kg who are not improving on current enzyme replacement therapy (late-onset Pompe disease).	Failure criteria: member does not meet diagnostic confirmation (enzyme assay, DNA testing, or increased lysosomal glycogen), age ≥ 18, or weight ≥ 40 kg; concurrent use with Lumizyme or Nexviazyme is not permitted. Dosing limits: ≥50 kg — Pombiliti 20 mg/kg + Opfolda 260 mg (4 capsules) every other week; 40 to <50 kg — Pombiliti 20 mg/kg + Opfolda 195 mg (3 capsules) every other week.

Section	Note
Template / continued therapy updates	Policy history documents that template changes were applied to other diagnoses/indications and the continued therapy section; no explicit additional step therapy sequence is provided in the excerpt.
Operational coding update	Policy history notes addition of HCPCS/J codes G0138, J1202, J1203 and removal of C9399 and J3590 as part of updates reflected in the continued therapy/template revisions.

Quantity Limits

miglustat (Opfolda) quantity limit

Quantity limit (Opfolda for NPC)585 mg per day

cipaglucosidase alfa-atga (Pombiliti) + miglustat (Opfolda) dosing

Pombiliti regimenPombiliti 20 mg/kg IV every other week

Opfolda regimen (≥50 kg)Opfolda 260 mg (4 capsules) PO every other week

Opfolda regimen (40 to <50 kg)Opfolda 195 mg (3 capsules) PO every other week

Pombiliti (cipaglucosidase alfa-atga) product and dosing

Vial size

Site of Care

Note

Site of care — IV Pombiliti; oral Opfolda

Pombiliti is administered by IV infusion (infusion setting) while Opfolda is an oral capsule intended for outpatient or home administration; ensure authorizations and site‑of‑care documentation reflect these routes.

Pombiliti dosing is 20 mg/kg IV every other week (chunk 18).
Opfolda is oral (65 mg capsules) with weight‑based capsule dosing every other week (chunks 18, 22).

Note

Administration setting — infusion for Pombiliti; oral for miglustat

Document that Pombiliti will be administered via IV infusion in a provider/supplier infusion setting and that miglustat (Opfolda) will be taken orally; billing should align with infusion and oral drug coding guidance.

G0138 describes intravenous infusion of cipaglucosidase alfa‑atga including supervision of oral miglustat administration (chunk 22).
Dosage table specifies Pombiliti IV and Opfolda oral capsule dosing (chunk 18).

Definitions

Pombiliti + Opfolda — combination therapy

Therapy descriptionCombination therapy of hydrolytic lysosomal glycogen-specific recombinant human α‑glucosidase (cipaglucosidase alfa-atga) with an enzyme stabilizer (miglustat)

Indication contextIndicated for adult late-onset Pompe disease patients weighing ≥ 40 kg not improving on current ERT

Concomitant use requirementPolicy requires Pombiliti and Opfolda be prescribed together for Pompe disease initial and continued therapy

Abbreviations

6MWT6-minute walk test

ERTenzyme replacement therapy

Background

Pompe disease is caused by deficiency of the lysosomal enzyme acid α‑glucosidase (GAA), resulting in accumulation of glycogen with variable skeletal muscle, respiratory, and cardiac involvement. Late‑onset Pompe typically affects adolescents and adults and presents with progressive skeletal muscle weakness and respiratory compromise. The regimen described in this policy combines intravenous recombinant GAA (cipaglucosidase alfa‑atga, Pombiliti) with an oral enzyme stabilizer (miglustat, Opfolda) and is indicated for adult patients meeting the policy’s diagnostic and weight criteria.

OpenPayer

Cipaglucosidase alfa-atga + miglustat (Pombiliti + Opfolda) coverage