A one-off treatment with lovotibeglogene autotemcel (LentiGlobinTM) gene therapy leads to sustained production of the anti-sickling hemoglobin HbAT87Q in most red blood cells, resulting in less hemolysis and the complete resolution of severe vaso-occlusive events in patients with sickle cell disease. This is according to interim results from an ongoing phase 1/2 clinical trial.

Lovotibeglogene autotemcel, also known as lovo-cel, consists of autologous hematopoietic stem cells and progenitor cells expressing a modified HBB gene, which codes for HbAT87Q transplanted back into the patient’s body.

Read more about sickle cell disease therapies.

The phase 1/2 trial is a nonrandomized, open-label, multisite, single-dose study in adults and adolescents with severe sickle cell disease. The primary outcome measure is the proportion of patients achieving complete resolution of severe vaso-occlusive events between 6 and 18 months after infusion. 

In the present study, published in The New England Journal of Medicine, researchers report results obtained from a group of 35 patients with severe hemophilia who had at least 4 vaso-occlusive events in the 24 months prior to enrollment. 

According to these results, engraftment occurred in all patients and the median total hemoglobin levels increased from 8.5 g/dL at baseline to at least 11g/dL between 6 and 36 months post-infusion. Almost half (40%) of the total hemoglobin consisted of HbAT87Q and was distributed across a mean of 85% of red blood cells. The results also showed that markers of hemolysis were reduced following treatment.

In all patients who could be evaluated (25 patients), severe vaso-occlusive events were resolved. These patients had between 2 and 14 events per year in the 2 years before enrollment in the study. Three patients had a nonserious adverse event that was related or possibly related to the treatment but resolved within 1 week. The researchers reported there were no cases of hematologic cancer during up to 37.6 months of follow-up.

The trial is ongoing and is expected to be completed in February 2024.

References

Kanter J, Walters MC, Krishnamurti L, et al. Biologic and clinical efficacy of LentiGlobin for sickle cell disease. N Engl J Med. 2022;17;386(7):617-628. doi:10.1056/NEJMoa2117175

A study evaluating the safety and efficacy of bb1111 in severe sickle cell disease. US National Library of Medicine. Last updated December 29, 2021. Accessed March 4, 2022.