Dec 9, 2023 - Health

New sickle cell gene therapies pose cost and access questions

A patient suffering from complications of sickle cell disease gets an echocardiogram. Photo: Michael Williamson/The Washington Post via Getty Images.

The Food and Drug Administration took a big step toward ending the most common inherited blood disorder on Friday by approving a pair of gene therapies for sickle cell disease.

Yes, but: The one-time treatments are both grueling and could cost millions of dollars, raising questions about equity and access.

The big picture: The approvals of Casgevy and Lyfgenia mark a milestone in the treatment of a debilitating disease that affects an estimated 100,000 Americans, mostly of African descent, and 20 million people around the world.

  • The condition distorts red blood cells that become misshapen and stiff due to a genetic mutation, causing blockages and damaging organs and tissue. Patients experience sudden and severe pain attacks, known as pain crises.
  • Until now, they've have had to turn to bone marrow transplants. But the new therapies edit genes directly in a patient's body and expand the kinds of diseases and conditions researchers can target to other blood disorders, certain cancers and infectious diseases.
  • President Biden, in a statement, said the developments showed "tremendous promise for developing additional life-saving treatments and it gives hope to the millions of Americans who live with other rare diseases."

How it works: Casgevy, from Vertex Pharmaceuticals and CRISPR Therapeutics, is a one-time treatment in which stem cells are harvested from a patient's bone marrow, then edited to produce fetal hemoglobin, which can offset the effects of patients' defective hemoglobin.

  • It's the first FDA-approved therapy using the CRISPR gene-editing system, a kind of genetic scissors whose discovery won a Nobel Prize in 2020 and is being applied for a range of diseases and conditions.
  • Lyfgenia, from bluebird bio, uses a viral vector to modify the patient's stem cells and help the red blood cells produce normal hemoglobin.

The catch: The newly approved treatments aren't for everyone. Patients first have to undergo extensive chemotherapy to rid their bodies of the defective cells and make way for reengineered ones — a process that may not be appropriate for older or frail patients.

  • There's also the risk of "off target" edits that zero in on the wrong genetic sequence and could increase the risk of developing cancer. Patients who receive Casgevy and Lyfgenia will be tracked in long-term risk studies, and the label for Lyfgenia includes a black box warning about cancer risk.
  • And there's the not insubstantial issue of buy-in from members of a historically underserved Black population that's experienced discrimination at the hands of the American medical establishment and may be distrustful of new treatments.

What we're watching: How much the cost of the new treatments will pose challenges to commercial and public insurers and limits access to the cures.

  • Vertex said Casgevy will be priced at $2.2 million.
  • Bluebird set the wholesale price of Lyfgenia at $3.1 million.
  • The Institute for Clinical and Economic Review, which advises drugmakers and payers, estimated an appropriate price for Casgevy would be between $1.35 million and $2.05 million per patient.
  • About half of the people living with sickle cell are lower-income individuals on Medicaid. The Biden administration in September launched an effort to expand access and coverage to this cohort.
  • Longer term, researchers are looking at expanding access by creating treatments that would enable the gene editing to happen entirely inside the body, without the need for the stem cell harvesting and processing.
  • "We need to focus on ensuring all patients can benefit," said Michael Santos, senior vice president and chief population health science officer for the Foundation for the National Institutes of Health, which is involved in next-generation treatments.
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