For Wedam Minyila, hospital rooms have always meant blinding pain. “It’s like someone stuck a knife in me,” he says.
But for a brief moment on a recent December morning, Wedam, 19 and suffering from sickle cell anemia, allowed himself to believe what his doctors had been telling him for months: This visit could be the first step toward a cure. As one of the first patients in the world to undergo a commercial treatment for this genetic disease, he could begin to imagine a future without excruciating pain.
“I choose to partially believe it,” he said the day he entered Children’s National Hospital in Washington DC for his stem cell extraction, the first big step in the revolutionary gene therapy process for sickle cell anemia. “But that also comes with skepticism: Will it really work?”
It’s the same question sickle cell patients across the country have been asking since the Food and Drug Administration approved two gene therapies a little more than a year ago that could cure the symptoms of the disease.
Since then, only a few dozen patients across the United States have been able to access them. Bureaucratic hurdles, a multimillion-dollar price tag and patient concerns about serious side effects mean that only a limited number of hospitals have treated patients so far.
More than 100,000 people in the United States – 9 in 10 black – have sickle cell anemia. This inherited disease causes the normally round red blood cells to twist into a crescent or sickle shape. Sickle cells often build up in blood vessels, causing excruciating pain, stroke, organ damage, and shortened life. New gene therapies, one from Boston-based Vertex Pharmaceuticals and the other from Somerville-based Bluebird Bio, both in Massachusetts, offer a possible cure.
So Wedam overcame his skepticism and worked for months to get insurance approval and medical consultations.
“I know what it can mean to me,” he said quietly as a team of medical professionals began to crowd around his bed. “But until it happens, I’m not really as excited as everyone else.”
His mother, Sylvia, watched him from the corner of the room, holding her breath. “This is something new,” he said. “And I never thought we would be one of the pioneers. It seems unreal.”
But the first step in what she describes as her “miracle” was happening before her eyes: Nursing staff gave her son a medication to mobilize stem cells normally trapped in the bone marrow and make them flow into the bloodstream. A couple of hours later, Wedam was hooked up to what’s known as an apheresis machine, which draws blood from the body and then spins it at high speed to separate the millions of stem cells before returning the rest of the blood to the cells. veins.
Dr. Andrew Campell approached Wedam as the first light orange liquid containing his stem cells began to pool in an IV bag hanging next to him.
“You are one of the few in the country, and even the world, who has taken this big step: gene therapy,” said Campbell, director of the hospital’s Comprehensive Sickle Cell Program. “It took a lot of courage, because I know that this is still very new in the process.”
Wedam was unfazed. “I had to do it,” he said. “There was nothing I could pass up. So I really had no choice.”
A learning curve for hospitals
In the coming months, Wedam’s cells will be sent to a lab in Tennessee, where technicians will use a gene-editing tool called CRISPR to modify a gene in the stem cells so they make red blood cells that are less likely to develop sickle cell disease. and block blood flow, causing pain crises.
Wedam will need intensive chemotherapy to eliminate his existing stem cells and make room in his bone marrow for the gene-edited cells, which a team at Children’s National Hospital will reintroduce into his bloodstream intravenously.
“To be able to give a therapy that is a cure and will keep you out of the hospital and probably prolong life, is amazing,” said Dr. David Jacobsohn, chief of blood and marrow transplantation at Children’s National. “What we can offer now is very, very powerful compared to five or 10 years ago.”
Still, Jacobsohn acknowledged that few patients have started gene therapy treatment. At Children’s National, which jumped ahead of the competition after participating in clinical trials for Bluebird Bio, only 10 people, including Wedam, have started or completed the process. That’s from a group of about 1,500 sickle cell patients the team treats in the Washington area.
“At first, hospital leaders were very excited. They said, ‘We have dozens and dozens of eligible patients. We need to build more beds!’ And I have a feeling that eventually we will, but it’s not going to happen right away,” he said. “It has been a learning curve for the hospitals and for the insurance companies.”
Jacobsohn said his team is picking up speed to begin treating one or two patients a month, a pace he called “exciting.”
“This is a very high-risk treatment that requires high-dose chemotherapy with the potential for complications,” he explained. “So it’s not something we want to ramp up too quickly.”
Vertex Pharmaceuticals’ Casgevy treatment, which lasts one month, has a list price of $2.3 million. Bluebird Bio’s Lyfgenia has a list price of $3.1 million. None include the cost of care to stay in the hospital or chemotherapy.
To handle the high price, insurers have implemented extensive preauthorization procedures. Both pharmaceutical companies assured NBC News that they have not yet seen a “definitive denial” for their drugs.
The procedure is resource-intensive for the limited number of hospitals authorized to administer it, requiring several days in the hospital for stem cell collection and, months later, hospital stays of several weeks for chemotherapy and stem cell reintroduction, Jacobsohn noted. Meanwhile, the stem cell processing lab needs several months to genetically alter the cells and perform safety checks before sending them back to the hospital for infusion.
For patients like Wedam, there are other considerations as well. Intensive chemotherapy lasts four days and makes patients extremely sick and susceptible to infections. Many develop ulcerative sores in the mouth, throat and esophagus that make eating almost impossible. In the long term, chemotherapy increases the risk of cancer and infertility.
For all those reasons, only one patient has completed the process at City of Hope Children’s Cancer Center in Los Angeles. Dr. Leo Wang, a pediatric hematologist-oncologist at the center, says he expects that number to increase rapidly in the coming months after “early adopters” begin to show success.
“We’re very hopeful that acceptance will increase and become more acceptable to people who are maybe a little more risk-averse,” Wang said. “And we’ve already seen patients come and ask us about it and say, ‘ Well, I’d really like to talk to someone who’s been through this and get their perspective, and then I might be interested in doing it.’”
‘God, you did this for me’
That’s one of Wedam’s motivations for becoming an “early adopter.” “If all those people could look at me and see that it works, they would have some hope,” he said. “Even if it’s just a little bit.”
The disease has robbed him of his ability to do almost anything, including getting out of bed. But the idea of a cure makes him dream of one day becoming a filmmaker.
In the short term, his ambitions are much smaller: He would like to attend his college classes in person rather than online.
“Now, I don’t really keep in touch with most of my friends, so I might make new ones,” he said. “I could learn the material better if I were in person, asking the teacher real questions. “I think being a normal person, doing what a normal person would do, is what really excites me.”
The disease plagued the Minyila family for almost two decades. In addition to Wedam, his 14-year-old brother, Wekem, also has sickle cell anemia.
“He has taken almost everything,” said Sylvia Minyila. “He has taken our joy”
Wedam, he said, was once a happy child who loved school and dancing. But once his grief attacks began around high school, he said, he changed.
“He became withdrawn. “Anywhere there was bone, I could feel pain,” he added. “Anywhere you were in the house you could hear him moaning. And this is something I used to think about regularly: ‘Am I going to lose him?’ Because I was in a lot of pain.”
Until gene therapy, the only cure for sickle cell anemia was a stem cell transplant from a donor. That worked for Wekem after Sylvia discovered he was a match for her youngest son. After some scary complications, the procedure was successful.
But antibodies in Wedam’s bloodstream prevented him from receiving the same cure.
“I was ecstatic. I said, ‘God, you did this for me. But what about my other son?’” Sylvia recalled, with tears in her eyes. “I wanted the same for Wedam.”
The woman said that when doctors at Children’s Hospital called her a few months later to inform her that Wedam might be a good candidate for the new gene therapy, it felt like a double miracle: an answer to her prayers.
“The only thing I was asking was, ‘Is it curative? Is this something you will still have to take medication for? Are you going to have a pain crisis?’ They said, ‘No.’ And I said, ‘We’re ready. “We are ready.”
Wedam has seen his younger brother transform since his treatment, even using his newfound energy to learn to ride a bike. The excruciating pain before Wekem’s stem cell transplant had made it impossible.
Wekem assured that he is looking forward to seeing his older brother healthy.
“I feel like it changed the life he’s going to live,” Wekem said. “I really didn’t think there was going to be anything else available to us so that he could receive treatment and be cured.”
But Wedam remains skeptical. “Maybe 60%,” he mentioned about his chances of being cured.
Still, even with the life-threatening complications that can arise, if there’s any chance of a less painful future, it’s worth a try.
