FDA Approves Gene Therapy for Inherited Blood Disorder

Staff members at Oregon Health & Science University's Casey Eye Institute perform the first-ever in vivo CRISPR gene edit procedure on March 21, 2020. (OHSU/Kristyna Wentz-Graff)

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.

“Casgevy, a cell-based gene therapy,“ was approved ”for the treatment of patients 12 years of age and older with transfusion-dependent beta-thalassemia, an inherited disorder characterized by life-long anemia requiring frequent blood transfusions,” the FDA said in a Jan. 16 announcement.

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.

This is the second time the FDA has approved Casgevy. In December, the agency gave it the green light for treating patients aged 12 years and older with sickle cell disease, another inherited blood disorder.

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Casgevy was developed by biotech firm CRISPR Therapeutics and biopharmaceutical company Vertex Pharmaceuticals. The therapy is also called exagamglogene autotemcel, shortened to “exa-cel.”

Before the FDA approved Casgevy for sickle cell disease, documents from the agency raised concerns about potential negative consequences of unintended gene edits.

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.

Casgevy’s use for treating transfusion-dependent beta-thalassemia (TDT) was approved under the “Fast Track” process, which according to the FDA is designed to “facilitate the development, and expedite the review of drugs to treat serious conditions and fill an unmet medical need.”

The treatment also received the “Regenerative Medicine Advanced Therapy” designation that is granted to medications “intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition.”

“On the heels of the historic FDA approval of CASGEVY for sickle cell disease, it is exciting to now secure approval for TDT,” said Reshma Kewalramani, chief executive officer of Vertex.

“TDT patients deserve new, potentially curative treatment options, and we look forward to bringing CASGEVY to eligible patients who are waiting.”

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.

Casgevy will be administered only through authorized treatment centers that have experience in stem cell transplantation. The therapy is expected to be available in the United States this year at a cost of $2.2 million, Vertex told CNBC.

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.

According to Boston Children’s Hospital, around 300 million people globally have the “thalassemia trait,” putting them at risk of having children with some form of thalassemia.

More than 100,000 people worldwide have transfusion-dependent thalassemia, with at least 1,200 of them in the United States.

Following the FDA’s approval of Casgevy for transfusion-dependent beta-thalassemia on Jan. 16, Vertex’s stock price rose. The company’s shares opened on Jan. 16 at $431.78 and were trading at $437.55 as of 11:12 a.m. ET on Jan. 17.

During this period, shares of CRISPR fell from $63.20 to $62.43.

Like Casgevy, many gene editing medical applications are under development globally. While the technology holds a lot of promise, it presents many risks as well.

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.