FDA Approves First Gene Therapies for Treatment in Patients With Sickle Cell Disease

Last week, the FDA approved exagamglogene autotemcel (exa-cel; Casgevy), from Vertex Pharmaceuticals, and lovotibeglogene autotemcel (Lyfgenia), from bluebird bio, as the first cell-based gene therapies indicated for the treatment of sickle cell disease in patients aged 12 years and older.¹

Beyond sickle cell disease, the approval of exa-cel marks an innovative advancement in the field of gene therapy, as it has become the first FDA-approved treatment to utilize CRISPR/Cas₉ genome editing technology.

Sickle cell disease, the most common inherited red blood cell disorder in the United States, affects 1 out of every 365 Black or African American births and 1 out of every 16,300 Hispanic American births.² The FDA-approval of these landmark drugs represents a critical turning point in the ongoing effort to manage the disease.

“Sickle cell disease is a rare, debilitating and life-threatening blood disorder with significant unmet need, and we are excited to advance the field especially for individuals whose lives have been severely disrupted by the disease by approving 2 cell-based gene therapies today,” said Nicole Verdun, MD, director of the Office of Therapeutic Products within the FDA’s Center for Biologics and Research.¹ “Gene therapy holds the promise of delivering more targeted and effective treatments, especially for individuals with rare diseases where the current treatment options are limited.”

Some have called for an increased focus on accessibility to coincide with the drugs’ approval, citing current shortcomings that may threaten the drugs' full potential.

“The approval of the first gene therapies for [sickle cell disease] represent a tremendous step forward for the [sickle cell disease] community, which has been historically overlooked and underfunded. While these new gene therapies are potentially life-changing for individuals living with [sickle cell disease], they must be accessible to be effective,” said Robert A. Brodsky, MD, president of the American Society of Hematology, Johns Hopkins University.²

“Despite the recent progress in expanding [sickle cell disease] therapies, current treatments and treatment models do not adequately address the many barriers to care people living with [sickle cell disease] face, including access to providers that understand their condition, hydroxyurea for symptom management, pain medication during pain crises, and specialized and high-quality care,” he continued.²

The safety and effectiveness of exa-cel were confirmed in an ongoing single-arm, multi-center trial in adult and adolescent patients with sickle cell disease.¹ Among 31 patients treated with exa-cel who met sufficient conditions for evaluation, 29 (93.5%) satisfied the primary efficacy outcome, freedom from severe veno-occlusive disease episodes for at least 12 consecutive months during a 24-month follow up period. All treated patients included for evaluation underwent successful engraftment, and no patients experienced graft failure or graft rejection.

The safety and effectiveness of lovotibeglogene autotemcel was evaluated in a single-arm, 24-month multicenter study among patients with sickle cell disease and history of vaso-occlusive episodes aged between 12 and 50 years old.¹ Out of 32 patients, 28 (88%) satisfied the measure for effectiveness, based on complete resolution of vaso-occlusive episodes between 6 and 18 months after infusion with the drug.

Both exa-cel and lovotibeglogene autotemcel are made from the patients’ own blood stem cells, which undergo genetic modification and are administered back to the patient as a 1-time, single-dose infusion as part of a hematopoietic (blood) stem cell transplant. A study will evaluate the long-term safety and effectiveness of both exa-cel and lovotibeglogene autotemcel among patients who received the drugs.¹

References

1. FDA approves first gene therapies to treat patients with sickle cell disease. News release. FDA. December 8, 2023. Accessed December 12, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease

2. ASH statement on FDA’s approval of new sickle cell disease gene therapies. News release. American Society of Hematology. December 8, 2023. Accessed December 12, 2023. https://www.hematology.org/newsroom/press-releases/2023/ash-statement-on-fda-approval-of-new-sickle-cell-disease-gene-therapies