First patient begins FDA-approved sickle cell gene therapy

On Wednesday, Kendric Cromer, a 12-year-old boy from a Washington suburb, became the first person in the world with sickle cell disease to start a commercially approved gene therapy that could cure the disease.

For the approximately 20,000 people with sickle cell disease in the United States who qualify for treatment, the start of Kendric's months-long medical journey may offer hope. But it also signals the difficulties patients face when trying a pair of new treatments for sickle cell disease.

For a lucky few, like Kendric, treatment could make the life they longed for possible. As a solemn and shy teenager, he had learned that ordinary activities – riding a bicycle, going out on a cold day, playing football – could cause episodes of excruciating pain.

“Sickle cell anemia always steals my dreams and stops all the things I want to do,” she said. Now she feels as if she has the opportunity to lead a normal life.

Late last year, the Food and Drug Administration gave two companies permission to sell gene therapy to people with sickle cell anemia, a genetic disorder of the 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 them black. People are born with the disease when they inherit the mutated gene for the condition from each parent.

The treatment has helped patients in clinical trials, but Kendric is the first commercial patient for Bluebird Bio, a company in Somerville, Massachusetts. Another company, Vertex Pharmaceuticals of Boston, declined to say whether it has started treating any patients with its approved CRISPR gene-editing remedy.

Kendric, whose family health insurance agreed to cover the procedure, began treatment at Children's National Hospital in Washington. Wednesday's treatment was just the first step. Doctors removed stem cells from her bone marrow, which Bluebird will then genetically modify in a specialized laboratory to treat her.

It will take months. But before it gets started, Bluebird needs hundreds of millions of stem cells from Kendric, and if the first harvest, which takes six to eight hours, isn't enough, the company will try once or twice more.

If they still don't have enough, Kendric will have to spend another month preparing for another stem cell extraction.

The entire process is so complicated and time-consuming that Bluebird estimates it can process cells from only 85 to 105 patients each year – and this includes not only patients with sickle cell disease, but also patients with a much rarer disease – beta thalassemia – who can receive similar gene therapy.

Medical centers also have the capacity to handle only a limited number of gene therapy patients. Every person needs specialized and intensive care. After a patient's stem cells have been processed, the patient must remain in the hospital for a month. Most of the time, patients are seriously ill due to powerful chemotherapy.

Children's National can only accept about 10 gene therapy patients per year.

“This is a big effort,” said Dr. David Jacobsohn, chief of the medical center's blood and marrow transplant division.

Last week, Kendric came prepared for his stem cell collection: He spent many weeks in this hospital being treated for pain so severe that at his last visit, not even morphine and oxycodone could control it. He brought his special pillow with the Snoopy pillowcase that his grandmother gave him and his special Spider-Man blanket. And he had a goal.

“I want to heal,” he said.

Bone marrow stem cells, the source of all the body's red and white blood cells, are normally nestled in a person's bone marrow. But Kendric's doctors infused him with a drug, plerixafor, that released them and let them float through his circulatory system.

To isolate the stem cells, hospital staff members inserted a catheter into a vein in Kendric's chest and connected it to an apheresis machine, a box-like device next to his hospital bed. It spins the blood, separating it into layers: a layer of plasma, a layer of red blood cells, and a layer of stem cells.

Once enough stem cells are collected, they will be sent to Bluebird's lab in Allendale, NJ, where technicians will add a healthy hemoglobin gene to correct the mutated ones that cause sickle cell anemia.

They will send the modified cells back three months later. The goal is to provide Kendric with red blood cells that don't turn into fragile crescent shapes and get trapped in his blood vessels and organs.

Although it only takes a couple of 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 lists a price tag of $3.1 million for its gene therapy, called Lyfgenia. It is one of the highest prices ever for a treatment.

Despite the astronomical price and grueling process, medical centers have waiting lists of patients hoping for relief from a disease that can cause strokes, organ damage, bone damage, episodes of excruciating pain and shortened lives.

At Children's National, Dr. Jacobsohn said at least 20 patients were eligible and interested. The choice of who would go first depended on who was the sickest and who was insured.

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.

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 child would have a one in four chance of inheriting the mutated gene from each parent and having sickle cell anemia. They could terminate the pregnancy or risk it.

They decided to take a risk.

The news that Kendric had sickle cell anemia was devastating.

He had his first seizure when he was 3 years old. Sickle cell blood cells were trapped in his legs and feet. Their child was inconsolable, she was in so much pain that she Deborah could not even touch him.

She and Keith took him to Children's National.

“Little did we know that was our introduction to many emergency room visits,” Deborah said.

The painful crises became more and more serious. It seemed like anything could set them off: 10 minutes of volleyball, a dip in the pool. And when they occurred, Kendric sometimes needed five days or a week of hospital treatment to control the pain.

His parents always stayed with him. Deborah slept on a narrow bench in the hospital room. Keith was asleep in a chair.

“We wouldn't dream of leaving him,” Deborah said.

Eventually the disease began to cause serious damage. Kendric developed avascular necrosis in his hips: bone death that occurs when the bone is deprived of blood. The condition has spread to his back and shoulders. He began taking a large daily dose of gabapentin, a medicine for nerve pain.

His pain never subsided. One day he said to Deborah, “Mom, I suffer every single day.”

Kendric wants to be like other children, but fear of grief has held him back. He has become increasingly sedentary, spending his days on his iPad, watching anime or building elaborate Lego structures.

Despite his numerous absences, Kendric continued to study, maintaining an A average.

Deborah and Keith began to hope for gene therapy. But when they found out how much it would cost, they lost some hope.

But their insurer approved the treatment within weeks, they said.

Now it has begun.

“We always prayed for this day to come,” Deborah said. But, she added, “We are nervous to read the consensus and what will have to go through.”

Kendric, however, is looking ahead to the future. He wants to become a geneticist.

And, he said, “I want to play basketball.”

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