New data presented at the 66th American Society of Hematology (ASH) Annual Meeting & Exposition demonstrate the durable efficacy of Lyfgenia (lovotibeglogene autotemcel) gene therapy in patients with sickle cell disease (SCD). The findings indicate that the majority of patients treated with Lyfgenia in clinical trials remained free from vaso-occlusive events (VOEs) for a median of over 3.5 years.
Sustained Resolution of VOEs with Lyfgenia
The data, presented by Bluebird Bio, included results from 58 SCD patients who participated in the Phase 1/2 HGB-206 and Phase 3 HGB-210 clinical trials. All patients received Lyfgenia, a gene therapy that introduces a gene into the patient's blood stem cells to produce a sickling-resistant version of hemoglobin. This approach aims to reduce the frequency of VOEs, a common and debilitating complication of SCD.
The analysis focused on 38 patients who had experienced at least four VOEs in the two years prior to entering the trial and had been followed for at least 18 months post-treatment. Results showed that 86.8% (33 out of 38) of these patients were completely free from VOEs, and all but two experienced no severe vaso-occlusive events, with a median follow-up of over 3.5 years.
Notably, all 10 children and adolescents treated with Lyfgenia were completely free from VOEs, including severe events, as of the latest follow-up. These results highlight the potential of Lyfgenia to provide significant and lasting relief from the complications of SCD, particularly in younger patients.
Impact on Stroke Risk
Stroke is a severe complication of SCD, resulting from disrupted blood flow to the brain. A separate poster presentation at the ASH meeting evaluated the impact of Lyfgenia on stroke risk in patients with a history of stroke. The analysis included six patients with a history of overt stroke and 21 patients with a history of silent stroke prior to Lyfgenia treatment.
With a median follow-up time of up to 6.5 years, no patients experienced recurrent strokes following treatment with Lyfgenia, even after discontinuing transfusions. This finding is particularly significant, as these patients face a high risk of subsequent strokes, and transfusions alone provide limited protection.
Long-Term Hemoglobin Production and Safety
As of the most recent follow-up, all patients treated with Lyfgenia were producing the sickling-resistant version of hemoglobin, and average hemoglobin levels were within a normal range without the need for blood transfusions. The therapy's safety profile was consistent with SCD and the known effects of conditioning regimens used before stem cell transplantation.
According to Richard Colvin, MD, PhD, Bluebird’s chief medical officer, these data continue to distinguish Lyfgenia as the most deeply studied gene therapy for sickle cell disease, with the most patients treated, longest follow-up, and broadest range of clinical presentations evaluated across the field.
Stacey Rifkin-Zenenberg, a hematologist-oncologist from Hackensack Meridian Health in New Jersey, emphasized the durability of the clinical benefits, stating, "These data demonstrate that the significant clinical benefits of [Lyfgenia] for people living with sickle cell disease are durable through continued long-term follow-up."
