Exclusion criteria that preclude coverage include specified laboratory abnormalities, organ dysfunction, infectious or immunologic conditions, family history, and treatment contraindications. Specifically, members are excluded for any of the following: absolute neutrophil count (ANC) <1 × 10^9/L (<0.5 × 10^9/L for subjects receiving hydroxyurea); platelet count <100 × 10^9/L; baseline left ventricular ejection fraction (LVEF) <45%; estimated glomerular filtration rate (eGFR) <70 mL/min/1.73 m^2; history of iron overload or serum ferritin >1000 ng/mL with cardiac MRI T2* <10 ms; or advanced liver disease as defined by persistent transaminases/direct bilirubin >3× ULN, coagulation abnormality >1.5× ULN attributable to liver disease, MRI evidence of cirrhosis, MRI findings suggestive of active hepatitis/significant fibrosis/inconclusive cirrhosis, or liver iron concentration ≥15 mg/g (and biopsy evidence when indicated, including cirrhosis, bridging fibrosis, or significant active hepatitis).

Additional exclusion conditions include active clinically significant bacterial, viral, fungal, or parasitic infection; any prior or current malignancy except previously treated non–life‑threatening cured tumors; any prior or current immunodeficiency disorder; positive HIV‑1/2, detectable HBV DNA, detectable HTLV‑1/2, or detectable HCV viral load; >2 α‑globin gene deletions; inability to receive RBC transfusion; contraindication to plerixafor, busulfan, or anesthesia; an immediate family member with a known or suspected familial cancer syndrome; need for therapeutic anticoagulation during conditioning through platelet engraftment; clinically significant pulmonary hypertension requiring treatment or supplemental oxygen; pregnancy or breastfeeding; and a history of a significant bleeding disorder.

BSWHP considers only one treatment per lifetime to be medically necessary. Repeat administration of lovotibeglogene autotemcel (Lyfgenia) is considered experimental and investigational because effectiveness of repeat dosing has not been established.

Lovotibeglogene autotemcel for any indications not specifically listed in this policy is considered experimental and investigational and therefore not medically necessary, because effectiveness for other uses has not been established.

Coverage for lovotibeglogene autotemcel (Lyfgenia) is available when all policy-level eligibility requirements are met. Key requirements include: member age between 12 and 50 years; prescription by or consultation with a board‑certified hematologist; documented contraindication to exagamglogene (Casgevy); confirmed SCD genotype of βS/βS, βS/β0, or βS/β+ by molecular or genetic testing; performance status of Karnofsky ≥60% for persons ≥16 years or Lansky ≥60% for persons <16 years; attestation that therapy will be delivered at an activated qualified treatment center; evidence of hydroxyurea failure, intolerance, or contraindication; eligibility for autologous HSCT and absence of an available HLA‑matched related donor; no prior HSCT, gene therapy, or investigational cellular therapy for SCD; adherence to FDA‑approved dosing and administration; and history of ≥4 severe vaso‑occlusive events in the prior 2 years while on appropriate supportive care.

Requests must also demonstrate the member does not meet any exclusion conditions (laboratory thresholds, infections, malignancy, immunodeficiency, pregnancy/breastfeeding, family cancer syndrome, etc.) and that all required baseline organ assessments and labs meet the policy thresholds (ANC, platelets, LVEF, eGFR, ferritin and cardiac MRI T2*, liver assessment). Prior authorization is required and all requests are subject to review by a clinical pharmacist and medical director.

For prior authorization, submit documentation that supports each eligibility criterion: contraindication to exagamglogene, board‑certified hematologist involvement, age, performance status, confirmed SCD genotype (βS/βS, βS/β0, or βS/β+), attestation of treatment at an activated qualified treatment center, hydroxyurea failure/intolerance/contraindication, eligibility for aHSCT and lack of an HLA‑matched related donor, clinical records documenting ≥4 severe vaso‑occlusive events in the prior 2 years, and baseline laboratory and organ assessment results meeting policy thresholds (including ANC, platelet count, LVEF, eGFR, ferritin/cardiac MRI T2*, and liver studies).

Incomplete documentation or failure to meet ALL listed criteria may result in denial of the request.

Not covered: repeat administrations of lovotibeglogene autotemcel and use of lovotibeglogene for indications not described in this policy are considered experimental and investigational and are not medically necessary because effectiveness for these strategies has not been established.

Background: Sickle cell disease (SCD) is an inherited single‑gene hemoglobin disorder characterized by red blood cell sickling, hemolysis, vaso‑occlusion, and multiorgan complications that shorten life expectancy. Lovotibeglogene autotemcel (Lyfgenia) is an autologous CD34+ hematopoietic stem cell‑based gene therapy intended as a one‑time administration for patients ≥12 years with SCD and a history of recurrent vaso‑occlusive events; it introduces a modified β‑globin gene (A‑T87Q) to produce anti‑sickling hemoglobin and reduce HbS polymerization.