Revolutionary Gene Therapies for Sickle Cell Disease Approved by FDA

Lyfgenia and Casgevy, two novel cell-based gene treatments, have just been authorized by the FDA for the treatment of sickle cell disease (SCD) in individuals aged 12 and above. Casgevy, the first medication to use a novel genome editing approach, was authorized by the FDA—a watershed moment in medical history that heralded a new age of gene therapy.  

Sickle cell disease is a congenital blood illness that disproportionately affects African Americans and Hispanic Americans; it affects around 100,000 persons in the United States. The condition is distinguished by a mutation in the gene responsible for producing hemoglobin, the oxygen-carrying protein in red blood cells. Mutant red blood cells clog blood arteries and reduce tissue oxygen supply due to their aberrant crescent or “sickle” form.

As a result, crisis circumstances or vaso-occlusive events (VOEs) emerge, causing extreme discomfort, organ damage, and even death. Despite the fact that both medicines are groundbreaking, Casgevy is the first to use CRISPR/Cas9 genome editing technology in gene therapy. Casgevy is a therapy that alters hematopoietic stem cells using the CRISPR/Cas9 system for those who have periodic vaso-occlusive crises.

This approach has enabled the exact modification of DNA by deleting, adding, or replacing sequences. After being altered, stem cells are reintroduced into the body. Through a bone marrow transplant, they engraft and stimulate the production of extra fetal hemoglobin (HbF). Patients with sickle cell disease (SCD) are less likely to have VOEs, which assist in preventing red blood cell sickling since their HbF levels are more significant.  

Lyfgenia, the second gene therapy, alters DNA with a lentiviral vector. It develops HbAT87Q, a gene-therapy hemoglobin that works similarly to normal adult hemoglobin, by genetically editing the patient’s blood stem cells. This therapy is only for people who have had a history of vaso-occlusive events. Red blood cells containing HbAT87Q assist in preventing blood flow obstruction, lowering the risk of sickling.  

Casgevy and Lyfgenia are similar in that they both entail high-dose chemotherapy, known as myeloablative conditioning, followed by processing and reinfusion of the patient’s blood stem cells as a single-dose infusion. Conditioning the modified cells to replace the current bone marrow cells is critical to their success. A multicenter trial is now conducted to establish Casgevy’s efficacy and safety. There is only one arm to the trial.

The number of consecutive months without severe VOC episodes was the most important outcome of the 24-month follow-up period used to measure efficacy. During the specified follow-up period, 29 of 44 Casgevy-treated patients (93.5%) were successful in meeting this goal. Aches and pains in the muscles and joints, nausea, oral sores, and exhaustion were among the most prevalent adverse effects reported by patients.  

Lyfgenia was shown to be both safe and effective in a 24-month multicenter trial. The efficacy was determined by determining if the VOEs recovered entirely between 6 and 18 months after injection. This result was obtained by 88 of 32 patients, or 28%. The majority of the adverse effects were the same as with Casgevy, with the addition of a black box warning about the possibility of hematological malignancy.  

With the FDA’s clearance, these new cell-based gene therapies to combat terminal illnesses have taken a big step forward in medicine. These activities demonstrate the FDA’s commitment to aiding in the development of safe and effective medications for illnesses with significant ramifications for human health.

Casgevy and Lyfgenia were given the titles Orphan Drug, Fast Track, Regenerative Medicine Advanced Therapy, and Subject to Priority Review in recognition of their relevance in treating a potentially fatal illness.

Casgevy, manufactured by Vertex Pharmaceuticals Inc., and Lyfgenia, manufactured by Bluebird Bio Inc., have been approved by the Food and Drug Administration. Patients who have had these therapies will be followed over an extended length of time to determine the safety and efficacy of each therapy, allowing for ongoing monitoring and evaluation of these innovative medications. 

News Reference  

Commissioner, O. of the. (n.d.). FDA Approves First Gene Therapies to Treat Patients with Sickle Cell Disease. Retrieved from https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease