Sickle cell treatment made with gene editing wins UK approval

Regulators in Britain on Thursday approved the first treatment derived from CRISPR, the revolutionary gene editing method. The treatment, called Casgevy, is intended to cure sickle cell disease and a related condition, beta-thalassemia.

The manufacturers, Vertex Pharmaceuticals, based in Boston, and CRISPR Therapeutics, based in Switzerland, say around 2,000 patients in Britain with sickle cell disease or beta-thalassemia are expected to be eligible for its treatment.

The companies expect the Food and Drug Administration to approve Casgevy for sickle cell patients in the United States in early December. The agency will decide on beta-thalassemia approval next year.

In late December, the FDA is expected to approve a new sickle cell gene therapy by Bluebird Bio of Somerville, Massachusetts. This treatment does not depend on gene editing, but on a method that inserts new DNA into the genome.

Sickle cell disease is caused by a defective gene that leads to the production of abnormal hemoglobin, the oxygen-carrying component in red blood cells. The cells themselves become malformed, causing episodes of extreme pain. About 100,000 Americans, mostly black and Hispanic, are believed to have the disease.

In beta thalassemia, the defective gene leads to a deficiency of hemoglobin in the red blood cells. The condition is rare.

Casgevy relies on CRISPR to hack the DNA, activating a gene that produces an alternative form of hemoglobin. To receive sickle cell treatment, patients in the UK must be at least 12 years old and have experienced repeated episodes of extreme pain.

There is no upper age limit, nor are patients excluded because they have suffered too much organ damage from sickle cell disease, says Dr. David Altshuler, chief scientific officer of Vertex.

But patients should have no other options. Sickle cell disease can be cured with a bone marrow transplant, but few patients have compatible donors.

For people struggling with the disease, the Vertex and Bluebird treatments have been a long time coming. Pain is not the only complication; people with sickle cell disease also suffer from bone and organ damage and stroke. The misshapen blood cells do not survive for long, resulting in anemia.

Still, the CRISPR and Bluebird treatments are burdensome and require expertise that most hospitals lack.

Patients must receive intensive chemotherapy to clear their bone marrow of abnormal stem cells and make room for the genetically modified cells. Then patients must stay in a hospital for a month or more while their bone marrow regrows.

And gene editing is expensive. Vertex and CRISPR Therapeutics have not yet set a price in Britain — that will depend on discussions with those who will pay for it, said Stuart Arbuckle, executive vice president and chief operating officer at Vertex.

However, the price in the United States is expected to be millions of dollars per patient. However, sickle cell disease itself is expensive and is estimated to cost the U.S. healthcare system $3 billion per year.

In the United States, Bluebird has already approved a gene therapy for beta-thalassemia. It costs $2.8 million per patient.

Dr. Altshuler said Vertex was testing its sickle cell treatment in children ages 5 to 11, hoping to prevent the irreversible organ damage that occurs over time.

The company’s first sickle cell patient, Victoria Gray, said Thursday that the treatment changed her life.

Ms. Gray, a Walmart employee in Forest, Miss., was diagnosed with sickle cell disease when she was three months old and suffered a pain crisis. Those episodes became part of her life, resulting in frequent hospital admissions.

“I couldn’t achieve a lot of my dreams,” she said. “The smallest things – cold, changeable weather – landed me in hospital.”

She underwent the gene editing treatment in 2019, when she was 33. Now, she said, all her symptoms are gone.

“It marked a new beginning,” Ms Gray said. “It’s more than I could ever have imagined, having it all gone.”