On Wednesday, Kendric Cromer, a 12-year-old boy from suburban Washington, became the first person in the world with sickle cell disease to begin a commercially approved gene therapy that could cure the condition.
For the estimated 20,000 people with sickle cell disease in the United States who are eligible for the treatment, the start of Kendric's months-long medical journey could offer hope. But it also highlights the difficulties patients face when seeking out some new sickle cell treatments.
For a lucky few, like Kendric, the treatment could make possible the lives they've longed for. As a solemn and shy teenager, he had learned that ordinary activities – cycling, going outside on a cold day, playing football – could trigger episodes of searing pain.
“Sickle cell disease always steals my dreams and interrupts all the things I want to do,” he said. Now he feels like he has a chance at a normal life.
Late last year, the Food and Drug Administration said gave two companies permission to sell gene therapy to people with sickle cell disease – a genetic disorder of red blood cells that causes debilitating pain and other medical problems. An estimated 100,000 people in the United States have sickle cell disease, most of whom are black. People are born with the disease if they inherit the mutated gene for the condition from each parent.
The treatment helped patients in clinical trials, but Kendric is the first commercial patient for Bluebird Bio, a Somerville, Massachusetts-based company. Another company, Boston-based Vertex Therapeutics, declined to say whether it had started treatment for patients approved CRISPR-based gene editing cure.
Kendric – whose family insurance agreed to cover the procedure – began his treatment at Children's National Hospital in Washington. Wednesday's treatment was just the first step. Doctors removed his bone marrow stem cells, which Bluebird will then genetically modify in a specialized laboratory for his treatment.
That will take months. But before it starts, Bluebird will need hundreds of millions of stem cells from Kendric, and if the initial collection — which takes six to eight hours — isn't enough, the company will try one or two more times.
If there is still not enough, Kendric will have to prepare for another stem cell extraction for another month.
The entire process is so complicated and time-consuming that Bluebird estimates it can treat the cells of just 85 to 105 patients per year – and that includes not just sickle cell patients, but also patients with a much rarer disease – beta thalassemia – who have this can receive treatment. a similar gene therapy.
Medical centers also have the capacity to treat only a limited number of gene therapy patients. Every person needs expert and intensive care. After a patient's stem cells have been treated, the patient must stay in the hospital for a month. Most of that time, patients are seriously ill from powerful chemotherapy.
Children's National can only accept about 10 gene therapy patients per year.
“This is a major effort,” said Dr. David Jacobsohn, chief of the medical center's blood and bone marrow transplant division.
At the top of the waiting list
Last week Kendric was prepared for the stem cell collection. He spent many weeks in this hospital being treated for pain so severe that at his last visit even morphine and oxycodone could not control it. He brought his special pillow with a Snoopy pillowcase given to him by his grandmother and his special Spider-Man blanket. And he had a purpose.
“I want to be healed,” he said.
Bone marrow stem cells, the source of all the body's red and white blood cells, normally reside in a person's bone marrow. But Kendric's doctors gave him a drug, plerixafor, which loosened them and allowed them to float in his bloodstream.
To isolate the stem cells, hospital staff inserted a catheter into a vein in Kendric's chest and attached it to an apheresis machine, a box-shaped device next to his hospital bed. It spins blood and divides it into layers: a plasma layer, a red cell layer and a stem cell layer.
Once enough stem cells have been collected, they will be sent to Bluebird's laboratory in Allentown, NJ, where technicians will add a healthy hemoglobin gene to correct the mutated genes that cause his sickle cell disease.
Three months later they return the modified cells. The goal is to give Kendric red blood cells that don't turn into fragile crescent-shaped shapes and get trapped in his blood vessels and organs.
While it only takes a few days to add a new gene to stem cells, it takes weeks to complete testing for purity, potency and safety. Technicians must grow the cells in the laboratory before performing these tests.
Bluebird quotes a price of $3.1 million for its gene therapy, called Lyfgenia. It is one of the highest prices ever for a treatment.
In spite of the astronomical price and the grueling processmedical centers have waiting lists of patients hoping for relief from a disease that can cause strokes, organ damage, bone damage, episodes of agonizing pain and shortened lives.
At Children's National, Dr. Jacobsohn that at least twenty patients were eligible and interested. The choice of who would go first came down to who was sickest and whose insurance came through.
Kendric qualified on both counts. But even though his insurance quickly approved the treatment, the insurance payments are only part of what it will cost his family.
Opportunities and hope
Deborah Cromer, a real estate agent, and her husband, Keith, who works in law enforcement for the federal government, had no idea they might have a child with sickle cell disease.
They only found out when Deborah was pregnant with Kendric. Tests showed that their baby would have a one in four chance of inheriting the mutated gene from each parent and developing sickle cell disease. They can terminate the pregnancy or take a chance.
They decided to take a chance.
The news that Kendric had sickle cell disease was devastating.
He had his first crisis when he was three. Sickle-shaped blood cells were stuck in his legs and feet. Their baby was inconsolable and in so much pain that Deborah could not even touch him.
She and Keith took him to Children's National.
“Little did we know, this was our introduction to many ER visits,” Deborah said.
The pain crises became more and more severe. It seemed like anything could set them off: ten minutes of volleyball, a dip in a pool. And when they occurred, Kendric sometimes needed five days to a week of hospital treatment to control his pain.
His parents always stayed with him. Deborah slept on a narrow bench in the hospital room. Keith was sleeping in a chair.
“We would never dream of leaving him.” said Deborah.
Eventually the disease began to cause serious damage. Kendric developed avascular necrosis in his hips – bone death that occurs when the bone runs out of blood. The condition spread to his back and shoulders. He started taking a large daily dose of gabapentin, a drug for nerve pain.
His pain never stopped. One day he said to Deborah, “Mommy, I hurt every day.”
Kendric wants to be like other children, but the fear of pain crises holds him back. He became increasingly sedentary, spending his days on his iPad, watching anime or building elaborate Lego structures.
Despite his many absences, Kendric stayed in school, with an A average.
Deborah and Keith began hoping for gene therapy. But when they found out what it would cost, they lost some of their hope.
But their insurer approved the treatment within a few weeks, they said.
Now it has started.
“We always prayed for this day to come,” Deborah said. But she added: “We are nervous as we read through the consents and what he will have to go through.”
However, Kendric is looking forward to the future. He wants to become a geneticist.
And he said, “I want to play basketball.”