The U.S. Food and Drug Administration (FDA) has approved a gene therapy to treat an inherited blood disorder, even as the agency earlier expressed concerns about the technology leading to “unintended” gene edits.
A patient’s blood stem cells are extracted, modified, and transplanted back into the individual’s bone marrow where they attach and multiply.
Modified cells then boost the production of fetal hemoglobin, which facilitates oxygen delivery and decreases the severity of anemia.
The FDA noted that the therapy comes with certain side effects, the most common being mouth sores, decreased appetite, and febrile neutropenia—fever associated with a low level of certain white blood cells.
Exa-cel works by using CRISPR-Cas9 technology. The process involves cutting into DNA and then inserting small bits of new code into it as the cell tries to repair the DNA.
“Since unintended edits can disrupt gene expression,” it is critical that the specificity of the exa-cel’s targeting component “be thoroughly screened to ensure off-target genome editing is minimized,” the FDA said.
Side Effects Listed
Casgevy therapy comes with several side effects. As part of the treatment, the patient is given conditioning medicine, which Vertex claims could lead to infertility.“After receiving the conditioning medicine, it may not be possible for you to become pregnant or father a child,” the company said in a Jan. 16 press release.
The level of platelet cells in the body can decrease, reducing the ability of blood to clot. This may result in uncontrollable bleeding. The patient’s white blood cell level may also fall, “which may make you more susceptible to infection.”
The company recommends consulting a healthcare provider in case a person who received Casgevy therapy experiences fever, chills, infections, severe headache, abnormal or prolonged bleeding, and bleeding without injury like nosebleeds, coughing up blood, or bleeding from gums.
Vertex also advises Casgevy patients to avoid donating blood, organs, cells, or tissues anytime in the future.
Back in 2022, biotech firm Bluebird Bio’s Zynteglo was the first cell-based gene therapy that received FDA approval for treating adults and children with transfusion-dependent beta-thalassemia. The treatment was priced at $2.8 million.
More than 100,000 people worldwide have transfusion-dependent thalassemia, with at least 1,200 of them in the United States.
For one, genetic modifications can trigger unexpected health issues. There is also a possibility that the altered DNA of an individual is passed to future generations, which in the long term poses unknown risks to gene pools.
The technology also raises ethical concerns. Genetic modification can lead to eugenics, demand for designer babies, and alteration of human traits, raising questions about what should be allowed and what must be restricted.