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SAN DIEGO -- A one-time treatment with lovotibeglogene autotemcel (Lyfgenia, lovo-cel) achieved near complete resolution of severe pain crises in patients with sickle cell disease (SCD) in an analysis presented here.

Of 34 evaluable patients, 88.2% (95% CI 72.5-96.7) achieved complete resolution of all vaso-occlusive events (VOEs) and 94.1% (95% CI 80.3-99.3) experienced complete resolution of severe VOEs during a 6 to 18 month assessment period following lovo-cel infusion, reported Julie Kanter, MD, of the University of Alabama at Birmingham.

Patients who experienced any kind of acute pain event or vaso-occlusive event post-treatment experienced a reduction of at least 50% compared with baseline, as well as a reduction in hospital admissions (2.5 to 0.4) and days in hospital (15.75 to 2.20).

All 10 adolescents (≥12 years to <18 years) in the study experienced a complete resolution of VOEs during the assessment period, showing the therapy was also effective in younger patients.

"When you talk to the individuals who have experienced this therapy, they will tell you it is a life-changing, transformative therapy." Kanter said during press briefing at the annual meeting of the American Society of Hematology. "We will need to follow these individuals long term in sickle cell disease centers so that they can be appropriately followed and managed to confirm previous findings of the efficacy, safety, and patient experience with lovo-cel, including adolescent patients."

Patients underwent plerixafor mobilization and apheresis, followed by myeloablative busulfan conditioning and lovo-cel infusion. "What we are doing is inserting a gene that makes hemoglobin A (HBA) labeled with T87Q," Kanter explained. "This has a near identical oxygen affinity to wild-type adult healthy hemoglobin."

Regarding biologic response, "we couldn't ask for too much better," Kanter said, noting that median percent of HBA^T87Q of non-transfused total hemoglobin was 40% or more, representing the amount of healthy hemoglobin being produced from the gene therapy.

All patients maintained a stable hemoglobin level from 6 months to the last follow-up, with some maintaining that level up to 60 months. "So we are really talking about a highly durable therapy," Kanter said.

About 87% of patients achieved a globin response (a composite endpoint evaluating HbA^T87Q percentage and total hemoglobin), with all of those patients maintaining that response through the last follow-up.

No patients with a history of stroke experienced a stroke post-treatment.

Effectiveness was also demonstrated by quality of life results, Kanter said, with clinically meaningful improvements in pain intensity, pain interference, and fatigue reported in 57%, 64%, and 64% of patients, respectively. These outcomes "really demonstrate what is important to our patients and those individuals living with sickle cell," she said.

Most adverse events occurred within one year of lovo-cel infusion and were consistent with side effects exhibited with busulfan conditioning. Two patients had lovo-cel related serious AEs.

There were no cases of veno-occlusive liver disease, graft failure, or graft-versus-host disease, and there were no vector-related complications, no insertional oncogenesis, or vector-mediated replication-competent lentivirus. There was one death of a patient who had significant baseline SCD-related cardiopulmonary disease that was not considered related to lovo-cel.

"But it's important to highlight that many individuals came into this therapy with significant and/or organ complications, and this will really be something we need to follow long-term to understand how much this therapy can reverse or stabilize these complications."

This analysis included 47 patients with SCD and recurrent severe VOEs, or history of overt stroke (median age 23 years, 60% male) from 2 studies -- the phase and phase studies -- who received a lovo-cel infusion as of Feb 13, 2023. The median follow-up was 35.5 months.

Kanter noted the eligibility criteria changed during the course of the studies, starting with traditional SCD criteria such as hospitalizations, a history of stroke, significant cardiopulmonary disease, as well as VOEs, and then shifting to include only those individuals who had four VOEs in the last 2 years. "We wanted to enrich our population with those individuals who had experienced significant painful events," she said.

The FDA recently approved lovo-cel as one of the first gene therapies for the treatment of SCD, though approval of lovo-cel came with a black box warning concerning the risk of hematologic malignancy. The agency's approval of a second gene therapy -- exagamglogene autotemcel (Casgevy, exa-cel) -- came with no such warning.

When asked to comment, Kanter -- saying it was her personal opinion -- suggested the black box warning "should have been in both therapies."

"We've seen multiple reasons now that these individuals may be at increased risk ... at baseline and that there is a risk when you take out those cells and manufacture them, regardless of which therapy you're using," she said. "While it is applied to Bluebird Bio (the therapy's developer), due to the previous manufacturing process that's not being used, I think it's important to note that it's something we really need to pay attention to as we see this also in our allogeneic transplant setting."

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