Gene-editing therapy Casgevy approved in 2nd country: Bahrain

U.S. Food and Drug Administration decision on treatment expected this week

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

Share this article:

Share article via email
A woman makes an announcement using a megaphone.

Health regulators in the Kingdom of Bahrain have approved the gene-editing therapy Casgevy (exagamglogene autotemcel) to treat people with sickle cell disease (SCD) and transfusion-dependent beta thalassemia (TDT).

This decision makes Bahrain, a small island nation in the Persian Gulf, the second country to approve Casgevy. The therapy was approved in the U.K last month for adults and children, ages 12 and older, who are eligible for a stem cell transplant but lack a donor. Those with SCD also must have recurrent vaso-occlusive crises (VOCs).

Details on therapy eligibility among patients in Bahrain were not available.

“The approval of the use of Casgevy in Bahrain marks a significant turning point in the cluster of treatments on offer to Bahrainis. It is a testament to the country’s visionary leadership, dedication to innovation, and unwavering commitment to improving the lives of its citizens, while ushering in the highest quality of health care and wellbeing for them,” Ahmed Alansari, CEO of the country’s National Health Regulatory Authority, said in a press release.

Recommended Reading
An adult stands at the bedside of a child receiving an intravenous infusion in a hospital bed.

SCD linked to longer wait for kidney transplant in children, youth

Gene-editing sickle cell therapy works to restore fetal hemoglobin production

Jaleela Jawad, Bahrain’s Minister of Health, added that the approval “showcases Bahrain’s progressive approach to healthcare and its determination to remain at the forefront of scientific breakthroughs.”

Casgevy, also known as exa-cel, is under priority review for approval in the U.S., with a decision expected this week. Applications seeking the therapy’s approval in the European Union and Saudi Arabia also are under review.

Sickle cell is caused by mutations that lead to the production of an abnormal form of adult hemoglobin — the protein that red blood cells use to carry oxygen through the bloodstream. The abnormal protein forms clumps inside red blood cells, changing their shape and making it harder for them to circulate through blood vessels, which can lead to VOCs and other disease symptoms.

Casgevy is designed to increase the production of fetal hemoglobin, an alternative form of the protein usually only made during early fetal development and more effective at transporting oxygen than its adult counterpart. This is expected to lessen hemoglobin clumping.

The therapy entails collecting and engineering patients’ hematopoietic stem cells, which can be found in the bone marrow and are responsible for giving rise to new blood cells. Harvested cells are engineered using the CRISPR gene editing tool to increase fetal hemoglobin production. Then, the modified cells are returned to the patient via a stem cell transplant so they can give rise to new blood cells capable of producing fetal hemoglobin.

No VOCs for a year in 29 of 30 SCD patients treated in clinical trial

Regulatory approvals of Casgevy have been supported mainly by data from two ongoing Phase 1/2/3 clinical trials: one called CLIMB-121 (NCT03745287) that involved people with SCD, and another called CLIMB–111 (NCT03655678) in people with TDT. Participants who complete either study may enter an extension study called CLIMB-131 (NCT04208529) that’s collecting long-term safety data on the therapy.

CLIMB-121, due to end in October 2024, is assessing the safety and efficacy of a single dose of Casgevy in people with severe SCD who had at least two VOCs in each of the two years before enrollment.

According to trial data given the U.S. Food and Drug Administration, 29 out of 30 evaluable patients were free of VOCs in the first year after treatment with Casgevy, meeting CLIMB-121’s main goal.