Neighborhood Health Plan RI Lyfgenia Coverage

Coverage Criteria for Lyfgenia (lovotibeglogene autotemcel)

Initial Approval Criteria

Covered when ALL of the following are met

Age: Member is at least 12-50 years of age

Diagnosis: Confirmed diagnosis of sickle cell disease (includes genotypes βS/βS, βS/β0, βS/β+) by hemoglobin assay showing significant HbS OR identification of biallelic HBB pathogenic variants with at least one p.Glu6Val pathogenic variant by molecular genetic testing

Member must NOT have disease with more than two alpha-globin gene deletions

VOE frequency: Member experienced four or more vaso-occlusive events/crises (VOE/VOC) in the previous two years while adherent to recommended therapy>=4 VOEs in 2 years

VOE defined as facility visit for acute pain, acute chest syndrome, acute splenic or hepatic sequestration, or priapism >2 hours requiring interventions (e.g., opioids, NSAIDs, RBC transfusion)

Prior therapy / step therapy: Member has symptomatic disease despite treatment with hydroxyurea and formulary add-on therapy (e.g., crizanlizumab) OR has a contraindication to or is not indicated for Casgevy (exagamglogene autotemcel)

Medicare members previously treated with this medication within the past 365 days are not subject to step therapy requirements

Prior gene therapy and transplant history: Member has not received other gene therapy (e.g., exagamglogene autotemcel) and has no prior hematopoietic stem cell transplant

Requests after prior exagamglogene autotemcel will be evaluated case-by-case

HSCT candidacy and donor status: Member is a candidate for autologous HSCT (no major organ dysfunction) and does NOT have a known 10/10 HLA matched related donor willing to proceed to allogeneic HSCT

Transfusion and hematologic preparation: Member will be transfused at least twice (once each month) prior to mobilization to reach target hemoglobin 8-10 g/dL (and <12 g/dL) and <30% HbSHb 8-10 g/dL and <30% HbS

Mobilization and conditioning: Mobilization should occur using a CXCR4 agent (e.g., plerixafor) in the absence of G-CSF; myeloablative conditioning (e.g., busulfan) should not occur until Lyfgenia and back-up cell collection are received; Lyfgenia must be administered at least 48 hours after the last conditioning dose

Consider prophylaxis for hepatic VOD/SOS

Contraindications and concomitant therapies: No history of hypersensitivity to DMSO or dextran 40; HIV negative by non-PCR testing prior to mobilization; member will not receive listed concomitant therapies (e.g., hydroxyurea within 2 months prior to mobilization until apheresis completed, myelosuppressive chelators withheld 7 days prior and 6 months post-treatment, disease-modifying agents withheld 2 months prior to mobilization, prophylactic ART stopped ≥1 month prior to mobilization, G-CSF mobilization prohibited, erythropoietin withheld 2 months prior to mobilization)

Specific timing and agents are detailed in the policy

Treatment setting and provider: Member will undergo treatment at a manufacturer-approved Qualified Treatment Center and Lyfgenia is prescribed by or in consultation with a hematology specialist

Prior consideration and monitoring: Provider has considered seizure prophylaxis prior to myeloablative conditioning; member will be monitored periodically for hematologic malignancies after treatment

Dose and product requirements: Single-dose therapy only; Lyfgenia dose must contain at least 3.0 × 10^6 CD34+ cells/kg per infusion>= 3.0 x 10^6 CD34+ cells/kg

Mobilization and administration instructions per product labeling

Coverage contingent on FDA labeling and clinical criteria

Covered when use aligns with FDA-approved labeling and plan criteria adopted by P&T Committee; Medicare NCD/LCD take precedence.

Primary coverage conditions: Use must conform to FDA-approved labeling AND be consistent with relevant clinical literature; requests will be individually considered by the plan based on prescriber-submitted information

For Medicare members, applicable NCDs/LCDs/LCAs supersede plan criteria.

Coverage excludes members with more than two alpha-globin gene deletions and members who have a known 10/10 HLA matched related donor willing to proceed to allogeneic hematopoietic stem cell transplant; these situations remove eligibility for autologous gene therapy under this policy. Requests must also meet the policy’s contraindication and concurrent-therapy restrictions (for example, no history of hypersensitivity to DMSO or dextran 40, HIV negative testing prior to mobilization, and avoidance of prohibited concomitant agents such as G-CSF mobilization, certain myelosuppressive iron chelators, disease-modifying agents, and prophylactic ART during mobilization) as described in the initial approval criteria.

Providers should confirm the member is a candidate for autologous HSCT (no major organ dysfunction) and that required pre-treatment steps will be followed (for example, transfusions to achieve target hemoglobin and HbS thresholds, treatment at a manufacturer‑approved Qualified Treatment Center, and prescription by or consultation with a hematology specialist) because failure to meet these conditions will preclude coverage.

For Medicare members, coverage determinations for outpatient Part B drugs follow Medicare policy and any applicable National Coverage Determinations (NCDs) or Local Coverage Determinations (LCDs)/Local Coverage Articles (LCAs). Where an NCD or LCD/LCA exists and applies to the requested service, those Medicare determinations take precedence over the plan’s non‑Medicare criteria. Providers may search CMS NCD/LCD/LCA documents at https://www.cms.gov/medicare-coveragedatabase/search.aspx to confirm applicability.

Renewal or continued therapy with Lyfgenia is not covered under this policy. Coverage is limited to a single treatment course and coverage cannot be renewed.

Medicare determinations may render a requested use non‑covered if it is inconsistent with an applicable NCD, LCD, or LCA. When such Medicare guidance exists, the plan will follow those Medicare policies for Medicare members; providers should verify Medicare coverage rules before submitting a request for a Medicare beneficiary.

Billing and Diagnosis Codes

Covered HCPCS CodesHCPCSCovered

J3394

injection, lovotibeglogene autotemcel, per treatment

NDCNDCCovered

73554-1111xx

Lyfgenia NDC (20 mL infusion bag, frozen autologous CD34+ cells) (partial range)

Covered Diagnosis CodesICD-10Covered

D57.00	Hb-SS disease with crisis unspecified
D57.01	Hb-SS disease with acute chest syndrome
D57.02	Hb-SS disease with splenic sequestration
D57.03	Hb-SS disease with cerebral vascular involvement
D57.04	Hb-SS disease with crisis with other specified complication
D57.1	Sickle-cell disease without crisis
D57.20	Sickle-cell/Hb-C disease without crisis
D57.211	Sickle-cell/Hb-C disease with acute chest syndrome
D57.212	Sickle-cell/Hb-C disease with splenic sequestration
D57.213	Sickle-cell/Hb-C disease with cerebral vascular involvement

1–10 of 37

1/4

Medicare Part B covered diagnosis codesmixed

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

MAC jurisdictions and contractorsmixed

MAC Jurisdictions list

Medicare Part B Administrative Contractor jurisdictions and contractors as listed in the appendix (state/territory groupings mapped to contractors)

Minimum CD34+ cell dose

Minimum per-dose CD34+ cell contentMinimum recommended dose: >= 3.0 x 10^6 CD34+ cells/kg (single dose, may be supplied in one to four infusion bags)

Dose formatSingle dose for infusion containing a suspension of CD34+ cells in one to four infusion bags

Administration timing relative to conditioningLyfgenia must be administered at least 48 hours after the last dose of myeloablative conditioning

Provider Responsibilities and Authorization

Prior Authorization

Prior Authorization Required

Prior Authorization Required — single treatment course. Coverage is provided when the plan’s clinical criteria and required documentation are met. Requests without the required medical records will be denied.

Prior Authorization required prior to initiation
Single-course gene therapy authorization; coverage when clinical criteria satisfied

Step Therapy

Use Cost‑Effective Alternatives First

Use of cost‑effective alternatives is encouraged. The plan’s P&T‑adopted criteria prioritize safer and more cost‑effective therapies (e.g., hydroxyurea, formulary add‑on agents) before authorization of this therapy when clinically appropriate.

Step therapy implication: consider hydroxyurea and formulary add‑on therapy prior to approval where indicated
Medicare members: these criteria do not supersede applicable Medicare NCD/LCD/LCA — follow CMS policy when present

Genetic and Laboratory Requirements

HBB pathogenic variants / HbS

Required genetic confirmationIdentification of biallelic HBB pathogenic variants where at least one allele is p.Glu6Val on molecular genetic testing

Alternate diagnostic methodIdentification of significant quantities of HbS with or without an additional abnormal β-globin chain variant by hemoglobin assay

Included genotypesDocumented genotypes include βS/βS, βS/β0, or βS/β+

Key Definitions

Vaso-occlusive event (VOE/VOC) definition

Clinical setting requiredEvent requires a visit to a medical facility for evaluation with documentation of the diagnosis

Qualifying clinical diagnosesAcute pain, acute chest syndrome, acute splenic sequestration, acute hepatic sequestration, or priapism > 2 hours

Required interventionsInterventions such as opioid pain management, non-steroidal anti-inflammatory drugs (NSAIDs), or red blood cell (RBC) transfusion must be necessitated by the event

Background

Lyfgenia (lovotibeglogene autotemcel) is an autologous, ex vivo lentiviral vector gene therapy indicated for patients with sickle cell disease aged 12 years and older who have a history of vaso‑occlusive events. The product is supplied as one to four frozen infusion bags containing genetically modified autologous CD34+ cells and is administered as a single dose per treatment course (HCPCS code J3394).

Approval in this policy requires that treatment be delivered at a manufacturer‑approved Qualified Treatment Center, prescribed by or in consultation with a hematology specialist, and that the single infused dose meet the product specifications (including a minimum target CD34+ cell content per policy thresholds). Clinical benefit in the pivotal studies included marked reductions in vaso‑occlusive events, but treatment is associated with potential Grade ≥3 adverse events (for example, cytopenias, febrile neutropenia, stomatitis, and anemia) and requires specific pre‑treatment preparation and monitoring as described in the initial approval criteria.

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Lyfgenia (lovotibeglogene autotemcel) — coverage criteria for sickle cell disease