FDA approves gene therapies for sickle cell disease (with a warning)


The US Food and Drug Administration (FDA) has approved the first cell-based gene therapies for the treatment of sickle cell disease (SCD), Casgevy and Lyfgenia.

Casgevy, from Vertex Pharmaceuticals and CRISPR Therapeutics, is also the first FDA-approved treatment to use CRISPR gene editing technology.

However, the FDA added a black box warning for Lyfgenia due to the risk of blood cancer in these patients, which resulted in the value of stocks in Bluebird Bio dropping steeply since the approval on 8 December. The treatment is also more expensive than Casgevy, which may have led to some market concerns.

In a statement, the company explained that two patients treated with an earlier version of the therapy using a different manufacturing process and transplant procedure (Study 1, Group A) developed acute myeloid leukaemia (AML).

Bluebird has initiated a post-marketing long-term follow-up study to assess the risk of malignancies.

“SCD 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, Director of the Office of Therapeutic Products within the FDA’s Center for Biologics Evaluation and Research. “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.”


Casgevy, a cell-based gene therapy, is approved for the treatment of SCD in patients 12 years of age and older with recurrent vaso-occlusive crises (VOCs). The approval is the second marketing authorisation for Casgevy, which was given the OK by the UK’s Medicines and Healthcare Regulatory Agency (MHRA) in November.

A total of 44 patients were treated with Casgevy in clinical trials, though only 31 had sufficient follow-up time to be evaluable. Of these, 29 (93.5%) achieved the primary endpoint of freedom from severe VOC episodes for at least 12 consecutive months. No patients experienced graft failure or graft rejection.

“It has been remarkable to be part of this groundbreaking programme,” said Stephan Grupp, Section Chief of the Cellular Therapy and Transplant Section and Director of the Kelly Center for Cancer Immunotherapy at the Children’s Hospital of Philadelphia. “Casgevy has the potential to be a transformative treatment for patients, and I look forward to continuing the work to ensure eligible patients can access this therapy across the country.”


Lyfgenia uses a lentiviral vector for genetic modification and is approved for the treatment of patients 12 years of age and older with sickle cell disease and a history of vaso-occlusive events (VOEs).

With Lyfgenia, the patient’s blood stem cells are genetically modified to produce HbAT87Q, a gene-therapy derived haemoglobin that functions similarly to haemoglobin A. In trials, twenty-eight (88%) of 32 patients achieved complete resolution of VOEs between six and 18 months after infusion.

“After decades of waiting we finally have a therapy that addresses the underlying cause of this devastating disease,” said John Tisdale, Chief, Cellular and Molecular Therapeutics Branch at the National Heart, Lung, and Blood Institute (NHLBI), principal investigator on the HGB-206 study. “The development of this therapy has been marked by transparency and collaboration that laid the groundwork for other technologies to follow.”

Diana Spencer, Senior Digital Content Editor, DDW

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