Lovotibeglogene autotemcel (Lyfgenia) — coverage and authorization criteria for sickle cell disease
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Policy governs coverage and authorization requirements for lovotibeglogene autotemcel (Lyfgenia) intravenous infusion for patients with sickle cell disease (SCD) age 12–50, detailing medical necessity criteria, documentation, and coding for Blue Cross NC.
Added revenue codes 0891 and 0892 as applicable to the HCPCS code(s) for the policy.
Updated diagnostic confirmation options to include hemoglobin assay showing significant HbS OR molecular genetic testing showing biallelic HBB pathogenic variants with at least one p.Glu6Val allele.
Specified required discontinuation of disease-modifying SCD therapies at least 8 weeks prior to HSC mobilization and myeloablative conditioning.
Clarified HBV and HCV testing/acceptance: allows HBV-vaccinated (HBsAb-positive) patients who are negative for other HBV markers and allows HCV antibody-positive patients if HCV RNA/viral load is undetectable.
Medical Necessity and Coverage Criteria
Medical necessity criteria
Covered when ALL of the following are met:
Severe VOE defined as ≥24-hour hospital or ER observation visit or at least 2 day-unit/ER visits over 72 hours both requiring IV treatment; priapism counts if medical facility visits occur (4 episodes).
Medical record documentation required
Medical record documentation required
Medical record documentation required; distribution from specialty pharmacy provider may be required; contact Blue Cross NC to coordinate.
Exclusions that would preclude coverage include: HIV-1 or HIV-2 positivity (documentation required within the past 3 months); presence of genetic mutations that inactivate two or more α-globin genes; prior allogeneic hematopoietic stem cell transplantation; prior gene therapy for the requested/approved indications. Additional exclusionary conditions include active, clinically significant infection; prior or current malignancy or immunodeficiency (other than non-melanoma skin cancer); severe cerebral vasculopathy; advanced liver disease or liver iron concentration ≥15 mg/g unless biopsy shows no cirrhosis/active hepatitis/significant fibrosis; chronic kidney disease; iron overload defined as cardiac T2* <10 msec or LVEF <45%; and clinically significant pulmonary hypertension.
Situations considered not medically necessary include use in patients who do not meet the age limits (<12 or >50 years), lack required diagnostic confirmation of sickle cell disease (no hemoglobin assay showing significant HbS and no molecular genetic evidence of biallelic HBB variants with at least one p.Glu6Val allele or an acceptable prescriber-submitted rationale), failure to document the required frequency of severe vaso-occlusive events (<4 VOEs in 24 months), or lack of documentation of prior therapy failure/intolerance (no record of uncontrolled disease despite hydroxyurea or crizanlizumab, or absence of documented intolerance/contraindication). Coverage is also not supported when required laboratory, organ function, vaccine/viral testing, or specialist prescriber documentation is missing.
Billing and Coding
| J3394 | lovotibeglogene autotemcel (Lyfgenia) intravenous infusion |
| 0891 | Special Processed Drugs - FDA Approved Cell Therapy (revenue code) |
| 0892 | Special Processed Drugs - FDA Approved Gene Therapy (revenue code) |
Prior Authorization, Documentation, and Provider Requirements
Prior authorization required — document medical necessity and FDA‑label dosing
Prior authorization is required and the request must include documentation that the patient meets all medical necessity criteria and that the requested dose is within FDA‑labeled dosing and maximum units (maximum units = 1).
Required prior therapies — hydroxyurea or crizanlizumab trial or intolerance
Document prior therapy history demonstrating uncontrolled disease despite hydroxyurea OR crizanlizumab at any point in the past, or documentation of intolerance, FDA‑labeled contraindication, or hypersensitivity to hydroxyurea or crizanlizumab.
Required medical record documentation — diagnosis, genotype, VOE history, labs, specialist
Include medical record evidence of SCD diagnosis and diagnostic confirmation (hemoglobin assay showing significant HbS OR molecular genetic testing showing biallelic HBB pathogenic variants with at least one p.Glu6Val allele OR prescriber‑submitted written clinical rationale), genotype information or molecular testing results, VOE history, required labs and organ assessments, and documentation of specialist prescriber or consultation.
- Hemoglobin assay or molecular genetic testing results (or prescriber written clinical rationale) showing diagnostic confirmation
- Molecular genotype (βS/βS, βS/β0, or βS/β+) or prescriber rationale
- VOE history (≥4 severe VOEs in past 24 months) and supportive care measures
- Labs and organ assessments (ANC, platelets within 3 months; HBV/HCV testing; cardiac T2*/LVEF; liver iron concentration; renal function)
- Specialist prescriber or documented consultation
Missing required documentation — denial or delay risk
Failure to provide required documentation — including patient age, confirmed SCD diagnosis and diagnostic test results or prescriber rationale, genotype information, VOE frequency, prior therapy trial or intolerance, and required labs/organ assessments — may result in denial or delay of authorization.
- Age (12–50 years) and SCD diagnosis confirmation
- Hemoglobin assay or molecular genetic testing genotypes (or prescriber rationale)
- VOE history (≥4 severe VOEs in 24 months)
- Prior therapy documentation (hydroxyurea/crizanlizumab) or intolerance/contraindication
- Recent labs/assessments (ANC, platelets within 3 months; HBV/HCV status; liver/cardiac iron or LVEF)
Definitions and Key Terms
Background and Therapy Overview
Lovotibeglogene autotemcel (Lyfgenia) is an autologous, lentiviral vector–based gene therapy consisting of manipulated autologous CD34+ hematopoietic stem and progenitor cells collected after mobilization and administered as a one-time intravenous infusion following myeloablative conditioning. It is indicated for patients with sickle cell disease meeting the policy age criteria and clinical requirements, including documented SCD diagnosis, genotype confirmation or prescriber rationale, and a history of at least four severe vaso-occlusive events in 24 months. Treatment requires coordination of HSC mobilization, conditioning (e.g., busulfan), and a single lifetime dose with a minimum CD34+ cell dose of 3 x 10^6 CD34+ cells/kg and prior authorization.
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