First Gene Therapies Approved to Treat Adult, Pediatric Patients With Sickle Cell Disease

In December 2023, the FDA approved the first cell-based gene therapies for the treatment of sickle cell disease in patients aged 12 years and older, with one of the treatments utilizing a novel editing technology.

“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 two cell-based gene therapies today,” said Nicole Verdun, MD, director of the Office of Therapeutic Products within the FDA’s Center for Biologics Evaluation and Research, in a press release. “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.”

One of the treatments—Casvegy—uses CRISPR/Cas9, which is a type of genome editing technology that modifies a patient’s hematopoietic stem cells. It is approved for patients aged 12 years and older with recurrent vaso-occlusive crises (VOCs). The safety and efficacy of treatment was evaluated in an ongoing single-arm, multicenter trial that included adult and adolescent patients with sickle cell disease. A total of 44 patients were treated with the approved treatment. Of the 31 patients that had sufficient follow-up time, 29 (93.5%) did not experience severe VOC episodes for at least 12 months—the main outcome of the study.

The most common side effects reported were low levels of platelets and white blood cells, mouth sores, nausea, musculoskeletal pain, abdominal pain, vomiting, febrile neutropenia, headache, and itching.

The second approved treatment—Lyfgenia—uses a lentiviral vector for genetic modification and is approved for patients aged 12 years and older with sickle cell disease and a history of vaso-occlusive events. The approval follows a single-arm, 24-month multicenter study in patients aged between 12 and 50 years old. The analysis of the study found that 88% of patients achieved completed resolution of vaso-occlusive events after receiving treatment.

The common side effects of the treatment are stomatitis, low levels of platelets, white blood cells, and red blood cells, and febrile neutropenia.

Reference:
FDA approves first gene therapies to treat patients with sickle cell disease. News release. US Food and Drug Administration; December 8, 2023. Accessed March 19, 2024. www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease?utm_medium=email&utm_source=govdelivery