General Information

Lyfgenia (lovotibeglogene autotemcel) is an autologous hematopoietic stem cell-based gene therapy.

Lyfgenia is specifically indicated for the treatment of patients 12 years of age or older with sickle cell disease and a history of vaso-occlusive events. 

Dosing/Administration

• Lyfgenia is supplied as a suspension for intravenous infusion. For autologous use only. 
• Patients are required to undergo hematopoietic stem cell (HSC) mobilization followed by apheresis to obtain CD34+ cells for Lyfgenia manufacturing.
• Dosing of Lyfgenia is based on the number of CD34+ cells in the infusion bag(s) per kg of body weight. 
• The minimum recommended dose is 3 × 106 CD34+ cells/kg.
• Myeloablative conditioning must be administered before infusion of Lyfgenia. 
• Following myeloablative conditioning, allow a minimum of 48 hours of washout before Lyfgenia infusion. 
• Verify that the patient’s identity matches the unique patient identification information on the Lyfgenia infusion bag(s) prior to infusion.
• Do not sample, alter, irradiate, or refreeze Lyfgenia.
• Do not use an in-line blood filter or an infusion pump.
• Administer Lyfgenia within 4 hours after thawing.

Mechanism of Action

Lyfgenia works by permanently adding a functional β-globin gene to patients’ own hematopoietic (blood) stem cells (HSCs).

Lyfgenia adds functional copies of a modified βA-globin gene (threonine [T] replaced with glutamine [Q] at position 87, T87Q or βA-T87Q-globin) into patients’ hematopoietic stem cells (HSCs) through transduction of autologous CD34+ cells with BB305 LVV. After Lyfgenia infusion, the transduced CD34+ HSCs engraft in the bone marrow and differentiate to produce red blood cells containing biologically active βA-T87Q-globin that will combine with α-globin to produce functional Hb containing βA-T87Q-globin (HbAT87Q). βA-T87Q-globin can be distinguished from wildtype βA-globin and from βS -globin through reverse-phase high-performance liquid chromatography (RPHPLC) or ultra-high performance liquid chromatography (UPLC). HbAT87Q has similar oxygen-binding affinity and oxygen hemoglobin dissociation curve to wild type HbA, reduces intracellular and total hemoglobin S (HbS) levels, and is designed to sterically inhibit polymerization of HbS thereby limiting the sickling of red blood cells.

Side Effects

Adverse effects associated with the use of Lyfgenia may include, but are not limited to, the following:

• stomatitis
• thrombocytopenia
• neutropenia
• febrile neutropenia
• anemia
• leukopenia

The Lyfgenia drug label comes with the following Black Box Warning: Hematologic malignancy has occurred in patients treated with Lyfgenia. Monitor patients closely for evidence of malignancy through complete blood counts at least every 6 months and through integration site analysis at Months 6, 12, and as warranted. 

Clinical Trial Results

The FDA approval of Lyfgenia was based on data from patients from the Phase 1/2 HGB-206 study. Safety data supporting the application includes data from 54 patients who initiated stem cell collection. Efficacy for Lyfgenia was supported by data from 36 patients in the Phase 1/2 HGB-206 Group C study following enhancements to the treatment and manufacturing processes made through the course of the clinical development program. 32 patients were evaluable for the endpoints of complete resolution of VOEs and severe VOEs in the 6-18 months post-infusion including 8 adolescent patients. In this cohort:

• Severe vaso-occlusive events were resolved in 30/32 patients (94%)
• 28/32 patients (88.2%) experienced no vaso-occlusive events at all