Lovo-cel gene therapy shows near-complete VOE resolution in sickle cell disease

A single infusion of lovotibeglogene autotemcel (lovo-cel) resulted in near-complete resolution of vaso-occlusive events (VOEs) among patients with sickle cell disease (SCD), according to the combined analysis of phase I/II HGB-206 group C and phase III HGB-210 studies presented at ASH 2023.

Within 6–18 months following lovo-cel infusion, 88.2 percent of patients experienced complete resolution of all VOEs, while 94.1 percent had complete resolution of severe VOEs.

Among the 10 adolescents (aged ≥12 to <18 years) included in the study, 100 percent achieved complete resolution of both VOEs and severe VOEs.

Overall, the majority of patients remained free of VOE after a median follow-up of 35.5 months.

“This is a one-time, truly transformative treatment with lovo-cel resulting in near-complete resolution of VOEs and severe VOEs for all patients,” said lead author Dr Julie Kanter from the Division of Hematology and Oncology at the University of Alabama in Birmingham, Alabama, US.

On December 8, 2023, even before the current study was presented at ASH 2023, the FDA approved lovo-cel gene therapy as a treatment for SCD in patients aged ≥12 years with a history of VOEs, Kanter mentioned. [https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease]

Gene therapy with lovo-cel consists of autologous transplantation of hematopoietic stem and progenitor cells, which are transduced with the BB305 lentiviral vector encoding a modified β-globin gene that produces an antisickling haemoglobin, HbA^T87Q. [N Engl J Med 2022;386:617-628] “HbA^T87Q has near identical oxygen affinity to wild-type adult haemoglobin,” said Kanter.

The current study comprised 47 adult and adolescent patients (median age 23 years, 59.6 percent male) with SCD and recurrent severe VOEs who received a one-time infusion of lovo-cel. [ASH 2023, abstract 1051]

A total of 33 patients achieved globin response (defined as a composite endpoint evaluating HbA^T87Q percentage and total Hb), of whom all patients maintained stable HbA^T87Q levels from 6 months to the last follow-up.

Kanter noted that “biologic efficacy was sustained for up to 60 months, with patients demonstrating stable therapeutic levels of HbA^T87Q, increased levels of total Hb, and normalization of haemolysis markers.”

At 36 months, more than half of the participants reported clinically meaningful improvements in pain intensity (57 percent) and in pain interference and fatigue (64 percent each). “It is very important to discuss patient-reported outcomes because looking at these laboratory values, biologic outcomes, and VOEs are important, but what we all need to know is how our patients feel,” said Kanter.

In terms of safety, grade ≥3 treatment-emergent adverse events occurred in 93.6 percent of patients within 1 year after lovo-cel infusion, but these were generally consistent with busulfan conditioning, Kanter noted.

Of note, there were no cases of veno-occlusive liver disease, graft failure, or graft-versus-host disease reported.

“The safety profile of lovo-cel treatment is consistent with the underlying SCD and the known effects of myeloablative conditioning,” said Kanter.

“Using gene therapy through lovo-cel, we have been able to essentially rid individuals with SCD of VOEs. It results in normal Hb levels and people just feeling amazing,” she said in a press release.

Kanter also pointed out that many of these patients had significant diseases and end-organ complications prior to receiving this therapy, and that after undergoing this treatment, these  patients experienced “life-changing transformative therapy.”

“[However, we still] need to follow these individuals long-term in SCD centres … [in order] to confirm previously reported findings regarding its efficacy, safety, and patient experience with lovo-cel, including adolescent patients,” Kanter noted.