FDA approves treatments for sickle cell anemia – 12/09/2023 – Health

The FDA, the American agency that regulates medicines and foods, approved this Friday (8) the first gene editing therapy to be used in humans for sickle cell anemia, a debilitating blood disease caused by a single mutated gene.

The agency also approved a second treatment using conventional gene therapy for sickle cell anemia, which does not use gene editing.

For the 100,000 Americans with the disease, most of them Black, the approvals offer hope of finally living without an affliction that causes excruciating pain, organ damage and strokes.

While patients, their families, and their doctors welcome the FDA approvals, obtaining either treatment will be difficult and expensive.

“It’s practically a miracle that this is possible,” says Stephan Grupp, chief of the cell therapy and transplantation section at Children’s Hospital of Philadelphia. Grupp, who consults for Boston-based Vertex Pharmaceuticals, said his medical center hopes to begin treating patients with sickle cell anemia next year. But, he added, “I’m very realistic about how difficult this is.”

Obstacles to treatment are numerous: an extremely limited number of medical centers authorized to provide it, the requirement that each patient’s cells be edited or have a gene added individually, procedures so onerous that not everyone can tolerate them, and a multi-million dollar cost and potential insurance hurdles.

As a result, sickle cell experts have said that only a small fraction of patients in the United States should receive the new treatment (not to mention the millions of sickle cell patients abroad, especially in Africa, for whom it may be completely out of reach because of while).

The FDA estimates that about 20,000 patients aged 12 and over who have had episodes of debilitating pain will be eligible for the therapies.

The gene-editing treatment, called Exa-cel and using the brand name Casgevy, was jointly developed by Vertex and Crispr Therapeutics of Switzerland.

It uses Crispr, a Nobel Prize-winning gene editing tool, to cut patients’ DNA. For a small number of people in clinical trials, it corrected the effects of the mutation, which results in sickle- or crescent-shaped red blood cells that get stuck in blood vessels, blocking them. Casgevy is the first approved treatment that uses Crispr.

Patients will also require expensive, intensive medical care and long hospitalization.

The other treatment, called Lyfgenia and made by Bluebird Bio of Somerville, Massachusetts, uses a common gene therapy method to add a good hemoglobin gene to patients’ DNA.

Vertex says its price for editing a patient’s genes will be $2.2 million; for Bluebird Bio, it will be US$3.1 million. But living with the disease is also extremely costly — on average, $1.7 million for those with commercial insurance over the patient’s lifetime.

Patients themselves may pay about $44,000 out of pocket, on average, over their lifetime.

For patients and the doctors who treat them, it is tempting to think about being free from the complications of sickle cell anemia. So despite the many uncertainties, medical centers say they are compiling lists of interested patients who are ready to seek treatment when it becomes available.

“We’re talking about survival for the first time,” says Sharl Azar, medical director of the Comprehensive Sickle Cell Center at Massachusetts General Hospital. Patients, says Azar, who previously consulted for Vertex, are starting to hope that they might live into their 70s or 80s instead of dying young.

Opportunities and Obstacles

Treatment will begin with hospital visits to collect the patients’ bone marrow stem cells — the precursors to red blood cells that are treated to enable the production of healthy blood cells.

Stem cells must be released from the bone marrow into the blood before they can be collected. To release them, doctors inject patients with a medicine called plerixafor.

It can take months to obtain enough stem cells to send to a central facility for treatment. And Vertex has just one gene-editing facility in the United States, in Tennessee; and one in Europe, in Scotland. The Bluebird Bio facility is in New Jersey.

After editing a patient’s cells with Crispr, technicians perform a sequence of quality checks. About 16 weeks after the process begins, the cells will be sent back to the medical center to be infused into the patient, says Julie Kanter, director of the adult sickle cell anemia center at the University of Alabama at Birmingham.

At this point, doctors must cleanse the patient’s bone marrow with intensive chemotherapy to make way for the new cells. Patients remain in the hospital for a month or more while their edited stem cells repopulate their marrows, during which time they do not have a functional immune system. That’s if they can find a medical center that offers the new therapy. Most hospitals will not be able to offer Casgevy even if they want to. So far, Vertex has authorized only nine centers to provide its treatment. The company says it will eventually authorize about 50.

Bluebird Bio has 27 authorized centers and also plans to add more.

Gene-editing treatment is so challenging and resource-intensive that major medical centers say that even if they were authorized to provide it, they would likely only be able to treat a small number of patients per year. “We can’t do more than 10 a year,” said Kanter, who has consulted for Vertex and Bluebird Bio in the past.

Vertex has not revealed how many patient cells it will be able to edit each year, saying only that it is confident it can meet demand by the time the treatment is introduced. Bluebird Bio also did not reveal it.

But, according to Grupp, Bluebird’s gene therapy for thalassemia, a genetic disorder in which the body doesn’t produce enough hemoglobin, provides a clue.

Bluebird, he said, has only been able to treat the cells of 50 patients a year since the drug was approved in August 2022. And that’s “for the entire country,” Grupp said.

Insurance payments present another obstacle. Before treatment can begin, the patient’s insurance must agree to pay. That could take months, says David Jacobsohn, chief of the blood and bone marrow transplant division at Children’s National Hospital in Washington. Your medical center is among those authorized to provide Vertex and Bluebird Bio treatments.

Most patients with sickle cell anemia are insured through Medicaid, notes John DiPersio, director of the Center for Gene and Cell Immune Therapy at Washington University School of Medicine in St. Louis. DiPersio consults for Vertex and Bluebird.

“If every patient with sickle cell disease in Missouri was treated, the state could not afford it,” he said.

Another concern involves the unknowns about the new therapy. Although an FDA panel of experts concluded that the benefits outweigh the risks, doctors remain on the lookout for unexpected results.

“We don’t yet know what the long-term effects will be,” says DiPersio. “We don’t follow patients long enough, just a few years.”

And stem cells, he added, “will live forever,” so if Crispr or Bluebird’s gene therapy causes genetic damage, it will remain.

This article was originally published in The New York Times.