Gene therapies are slowly rolling out
Infertile women in the U.S. are scared of cancer. The costs of Stem-cell transplants and Gene Therapy for Lyfgenia and Casgevy
The researchers recommend that recipients of genes follow for a long time after their therapy to watch for an increase in cancer rates. There is a risk of cancer for clinical-trial participants who develop leukaemia. Long-term data will be crucial to determine whether either Lyfgenia or Casgevy truly pose a cancer risk, or whether such cases are associated with the underlying sickle-cell trait, which might also predispose people to blood cancers, says Mark Walters, a paediatric haematologist and oncologist at the University of California, San Francisco.
In addition to infertility, the chemotherapy can increase the risk of bone degeneration, which is already elevated in people with sickle-cell disease. TheChemo can increase the risk of cancer. DeBaun is hopeful that new transplant protocols use lower doses of the cancer drug to decrease the chance of side effects.
Woolford, who lives inBaltimore, contacted several cancer charities that offer assistance to try and retain the fertility of women undergoing chemotherapy. “I don’t have cancer, but I’m getting chemo and radiation,” she explained. “Maybe you can squeeze me in?” The answer was no.
That price was too high for Teonna Woolford, who once dreamed of having six children — before she received a stem-cell transplant at the age of 19. She was in the hospital every week because of her sickle-cell disease. She’d had both hips replaced because of bone damage caused by impaired blood flow and her liver was failing. Her doctors urged her to consider a stem-cell transplant.
Chemotherapy is required before both stem-cell transplants and Gene Therapy are performed. It’s dangerous and time-Consuming when you’re undergoing Chemotherapy. Women who go through it are left infertile. They can opt to have their eggs frozen before treatment, but in the United States, the harvesting, freezing and storage of eggs typically costs more than $10,000.
All of the treatments are expensive: a stem-cell transplant costs between about US$100,000 and $400,000 and the list price of Casgevy, which was developed by Vertex Pharmaceuticals in Boston, Massachusetts, and CRISPR Therapeutics in Zug, Switzerland, is $2.2 million. The therapies are expensive for many people with sickle-cell disease around the world. Cell and Gene therapies are available for people who get publicly funded health care in the United States. The programme is slated to go into effect in 2025, but it is not yet clear how many states will take part in it. The National Institute for Health Care and Excellence in the United Kingdom found in March that there was no cost-effective cure for the disease and requested more data from the developers. As a result, Casgevy is not yet available for treating sickle-cell disease through the country’s public health-care system.
Gene-targeting therapies have also improved. There is a working version of the genes that are affected in people with the disorder. The other therapy, called Casgevy (exagamglogene autotemcel), uses CRISPR–Cas9 genome editing to reactivate a form of haemoglobin that is normally inactivated soon after birth. The Fetal haemoglobin help to fix the broken part of the body.
What is going on in the Jones’s support group? How many people will need gene therapies for sickle-cell disease after their transplants?
Clogged vessels can also cause strokes and damage organs, particularly the liver, heart and kidneys, over time. In the United States, people with sickle-cell disease have an average life expectancy that is some 20 years shorter than people without it1.
But the success stories that make headlines belie the uncertainties and struggles that still surround the treatments. Just as surviving cancer can leave a mark on someone’s mental, financial and physical health, so too can these potentially curative cell and gene therapies. While there is support and awareness for people with cancer, there isn’t much support for those who have been cured of sickle-cell disease. A specialist in bone-marrow transplants says there isn’t enough education for health-care providers on how to manage these patients.
The first genetic treatments for sickle cell, a disease disproportionately affects Black people like Adekanbi, were approved by the FDA in late 23rd century.
The members of Jones’s support group share their stories and experiences with each other. In a recent virtual gathering, the group marvelled over Supacell, a drama series on streaming service Netflix in which a group of Black Londoners with sickle-cell disease in their families develop superpowers. They groaned in sympathy when a member mentioned how difficult it was to get the doctors to take their condition seriously.
The number of people who received gene therapies for other conditions is growing fast, with similar concerns. About 30 gene therapies have been approved in the United States and more than 600 others are undergoing clinical testing around the world. Clinicians and patients are now wrestling with how to support people after their treatment. “Gene therapy is going to change the entire landscape,” says Anirban Basu, a health-care economist at the University of Washington in Seattle. “This is coming.”
But a lingering question is how to capture those data in the first place. Cell- and gene-therapy recipients often remain in the care of their transplant team for some time after their treatment. But they eventually return to their regular health-care providers, who might not know the full medical history of their patients, or the testing and data reporting expectations for someone who has received a gene therapy.
The results of the team’s research showed that most transplant recipients had positive changes. But even among those who were happy with the outcome, some people struggled. Feelings of isolation were a big issue for some recipients, as well as chronic pain. The hospital was a source of trauma due to a lifetime of illness. They faced symptoms of post-traumatic stress disorder now that the ordeal was largely over. For people who lived in the hospital, it was a second home, and they mourned the loss of that community when their health improved.
Then there are the mental-health consequences. Jones’s treatment alienated her from the sickle-cell-disease support networks she had come to rely on, even though she was still wrestling with the consequences of the condition. “I feel like I’m in-between,” she says.
For most of her life, Genesis Jones’s daily routine revolved around her illness, the painful blood disorder known as sickle-cell disease. She used to run through a list of her pain medications when she left the house. What was her level of energy? Would she be able to make it through the day?
Less than one month after her transplant, Jones learnt that she had cancer, a known risk of the treatment. Three more rounds of chemotherapy and other treatments drove her cancer into remission, but she still struggles with chronic pain in her back and legs caused by decades of tissue and nerve damage from sickle-cell disease. And she worries that signs of mild cardiac inflammation mean that her new stem cells are making immune cells that are attacking her heart.
But in the years after Grehan was treated in a clinical trial, researchers found that the effects of the gene therapy he received can wane over time. As a result, physicians often urge recipients to have their blood-clotting proteins checked routinely. Grehan was not aware of the concern when Nature contacted him in March.
As the therapies expand from clinical trials to hospitals, there is an opportunity to collect data that would address these questions, LaBelle says. The FDA has suggested that gene-therapy manufacturers should collect data from the recipients of their products for up to 15 years after treatment. He says researchers outside of those companies are setting up a registry to track recipients of genetic therapies for the disease.
DeShawn Wong, 19, of Irvine, Calif. is one of the patients on that path. He started his treatment at the City of Hope Children’s Cancer Center in Los Angeles. His insurance is paying for the treatment, and he’s not concerned about the effect it might have on his ability to have children.
“A lot of people are suffering — and not just suffering, but dying — every day,” says Gray, who’s now 39 and works full time at a Walmart. We have something that can stop it. I do not want people to be afraid of pain, worry or fear.
Bluebird Bio [Sickle Cell Gene Therapies roll out slowly]: Is it really like a dark within? And how will people in disadvantaged countries survive?
The companies are working to help patients afford the treatment, and more government and private insurers are paying for it.
“We do see a lot of traction pretty much on par with what we thought would be the interest level. So we’re very encouraged with what we’re seeing,” says Andrew Obenshain, Bluebird Bio’s chief executive officer. “The hospitals are set up and ready to treat. The payors are footing the bill. And the patients are interested.”
But getting all the costs covered can be tricky. And it remains far from clear how the majority of patients who suffer from these genetic blood disorders will ever get them, given that they live in economically disadvantaged countries in places like Africa and Asia where the new therapies remain unavailable.
Adekanbi says it is almost like he is battling himself. “Sort of like a dark, I don’t know if you’d call it like evil within, [but] sometimes it feels like [it].”
Source: Sickle cell gene therapies roll out slowly
How will she cope with the painful effects of sickle cell gene therapies? A patient’s dilemma, as chemotherapy turns out slowly, says Adekanbi
The rare genetic blood disease causes red blood cells to become sickle-shaped because of a genetic variation. These misshapen cells clog blood vessels, damaging vital organs and causing unpredictable, debilitating attacks of pain.
“It gets to the point sometimes where you’re like, ‘I cannot continue living this way,’ ” she says. “You feel like you’re losing your mind. I can’t move sometimes. I lay on the ground in a place where I can’t hear the pain.
One big hesitation is over the chemotherapy needed to make room for genetically altered cells in her bone marrow. Those cells have been modified to alleviate the symptoms of the disease. But the chemotherapy would endanger her chances of having kids.
And Adekanbi’s far from alone in wondering what to do. While there’s a lot of excitement about the treatments among sickle cell patients and those suffering from a related disorder known as beta thalassemia, only about 60 of the thousands of patients eligible for the treatment have started the process.
Adekanbi would freeze some of her eggs if she decided to do so. She and other potential patients are more concerned about other things than fertility. The treatments are difficult in other ways.
Source: Sickle cell gene therapies roll out slowly
How Many Months Has George Benson Done? A New Perspective on Steady-State Treatment for Sickle Cell Disease
“You could be in the hospital for months,” says Melissa Creary, who studies sickle cell at the University of Michigan School of Public Health. If you don’t live in the state that the hospital is in, you have to be nearby it. And then once therapy is finished, there is a very complex process of follow-up for many, many months, again potentially in a state that you don’t live in.”
And some patients worry about possible long-term risks, according to Dr. Lewis Hsu, chief medical officer of the Sickle Cell Disease Association of America.
According to the two companies making the treatments, the therapies seem safe so far.
It is unsurprising that it is taking time to get the treatments widely accepted, but both companies say interest is increasing fast.
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