An advisory committee of the US Food and Drug Administration (FDA), the agency that regulates medication in the United States, agreed on Tuesday that a CRISPR drug for sickle cell disease is safe. The medication, called Exa-cel, could be approved for sale by early December.
It would mark the first CRISPR treatment deemed acceptable for clinical use on a genetic disease if approved.
Globally, more than 7.7 million people live with sickle cell disease, which overwhelmingly impacts people of African or Caribbean descent.
Sickle cell has a high mortality rate, especially among children — it is the 12th leading cause of death in kids under five globally. In general, sickle cell patients die around 20 years earlier compared to the average population.
How sickle cell disease impacts the body
Sickle cell patients have elongated blood cells that resemble sickles rather than the typical donut-shape of normal blood cells. These misshaped cells can get stuck in the blood vessels and block oxygen supply, causing patients to experience excruciating pain, strokes and organ damage. It is often impossible to predict when pain will start.
A 42-year-old sickle cell patient, who spoke at the advisory committee meeting on Tuesday but did not provide his name, said the disease has had an enormous impact on his life — not only physically, but financially. He said he spends more than $10,000 (€9,409) per year on medical treatments. He was diagnosed with sickle cell at the age of two.
"I had pneumonia as a kid. I had my gallbladder removed as a kid and I dealt with excruciating pain crises that would have me in and out of hospital for days to weeks at a time because the pain was so excruciating," he said.
Even on pain medications like Percocet, he said, he often "felt like I was being hit with a hammer." The only way to deal with his pain was through frequent hospital visits, which he said took an enormous toll on his family.
He said he still experiences strong pain so frequently he has to go to the hospital; pain that, if it's in his legs, prevents him from even being able to walk across the room.
How the CRISPR treatment works
At Tuesday's meeting, Vertex Pharmaceuticals and CRISPR Therapeutics researchers presented the findings of their Exa-cel clinical trial. Of the 32 participants, 31 hadn't experienced a pain crisis nine months after the treatment.
The treatment works like this: A person's stem cells are removed, then those cells are treated with exa-cel in a lab, which, using the CRISPR gene editing tool, essentially cuts out the sections of DNA that cause the sickle shape. The patient receives chemotherapy to rid the body of the sickle cells. The treated stem cells are reintroduced into the body.
The treatment alters a person's own blood cells using the CRISPR gene editing tool, which cuts out sections of a patient's DNA to delete the mutation causing the sickle shape. The process requires over a month's stay in the hospital and chemotherapy.
Right now, there is only one approved cure for sickle cell disease: bone marrow transplant. But it can be very hard for sickle cell disease patients to find suitable donors for this procedure, which comes with a number of potential complications.
The fact the CRISPR treatment doesn't have a donor requirement makes it attractive to patients and doctors, experts say.
"The potential of gene editing treatments for sickle cell disease would be of tremendous benefit to individuals suffering from this painful condition," said Edward Ivy, Vice Chief Medical Officer of the Sickle Cell Disease Association of America. But, he added, the potential risk benefit analysis must continue to be evaluated.
A treatment for a certain type of patient
James Taylor, director of the Howard University Center for Sickle Cell Disease in Washington DC, said that although this treatment is an exciting development, he told DW, he has reservations.
"They have evaluated 30 patients. It's not a large number," he said.
He said the pool of patients treated was very specific, which could mean results may not transfer to others.
"It's always important to look at how the trials were run; and what they excluded are any patients who had more than 10 painful episodes a year,” he said, explaining this isn't fully representative of the adult population of people with sickle cell disease. Many, he said, have many more episodes annually.
He also said the cost of the treatment — estimates are around $2 million (€1.882.390) per person — is prohibitively high.
"You're dealing with a patient population that, at least once they become adults, they're almost always on public assistance programs," he said.
He added that the majority of patients who have sickle cell disease in the US live in areas very far away from the facilities that would be able to perform the CRISPR therapy. Most treatment centers are located in the northeast of the US and the west, while the vast majority of US patients are concentrated in the south. And, he said, the bulk of people who experience this disease aren't located in the US or Europe at all — they're in Africa, where CRISPR facilities are sparse, if not non-existent.
Many on Tuesday's committee shared similar concerns about affordability and access to the drug should it be approved. And although Exa-cel has been effective among patients over a relatively short period of time, it is unclear whether it will remain so in the long run. Others have expressed concern that the CRISPR scissor-like tool will cut out unintended parts of patients' DNA, causing complications.
However, given all the unknown, the FDA advisory committee members seemed generally supportive of getting the treatment out sooner rather than later.
"We want to be careful to not let the perfect be the enemy of the good," said committee member Gil Wolfe, a professor of neurology at the University of Buffalo in the US state of New York.