The US Food and Drug Administration (FDA) has approved Vertex Pharmaceuticals/CRISPR Therapeutics and bluebird bio’s respective gene therapies to treat sickle cell disease (SCD) in patients aged 12 years and older.
Affecting approximately 100,000 people in the US, SCD is a life-long, genetic disease that causes red blood cells to take a distinct crescent shape, which can block blood vessels and affect the way oxygen is carried around the body.
The disease can cause serious health problems, including severe pain and organ damage called vaso-occlusive events (VOEs) or vaso-occlusive crises (VOCs).
Vertex/CRISPR’s Casgevy (exagamglogene autotemcel), which is now the first CRISPR-based gene-editing therapy to be approved in the US, has been authorised for use in patients who experience recurrent VOCs, while bluebird’s Lyfgenia (lovotibeglogene autotemcel) has been approved for those with a history of VOEs.
Both therapies are made from patients’ own blood stem cells, which are modified and then given back as a one-time, single-dose infusion as part of a blood stem cell transplant.
The FDA’s decision on Casgevy, which uses ‘molecular scissors’ to trim faulty parts of genes that can then be disabled or replaced with new strands of normal DNA, was supported by an ongoing single-arm, multi-centre trial in adult and adolescent patients with SCD who had a history of at least two protocol-defined severe VOCs during each of the two years prior to screening.
Of 31 evaluable patients, 29 achieved the study’s primary efficacy outcome of freedom from severe VOC episodes for at least 12 consecutive months during the 24-month follow-up period.
The regulator’s approval of Lyfgenia, which inserts modified genes into the body through disabled viruses, was based on data from a single-arm, 24-month multi-centre study in patients with SCD and a history of VOEs between the ages of 12 and 50 years.
Effectiveness was evaluated based on the complete resolution of VOEs between six and 18 months after infusion with Lyfgenia, with 28 of 32 patients achieving this.
Reshma Kewalramani, chief executive officer and president of Vertex, described the US approval of Casgevy as “momentous”.
“It is the first CRISPR-based gene-editing therapy to be approved in the US. As importantly, Casgevy is a first-in-class treatment that offers the potential of a one-time transformative therapy for eligible patients with SCD,” said Kewalramani.
Sharing a similar sentiment, Andrew Obenshain, chief executive officer of bluebird, said: “Bringing Lyfgenia to people living with SCD is a milestone that bluebird has been working toward for almost a decade – and one that members of the SCD community have been waiting on for much longer.”