When Great Ormond Street hospital (Gosh) published the results of his gene therapy trial for “bubble baby” syndrome was considered a medical breakthrough. The treatment has had a more than 95% success rate for treating the life-threatening disorder in which children have no immune system. But less than a year later, the therapy was abandoned by the pharmaceutical company that had planned to bring it to market.
Now Gosh is taking the unprecedented step of trying to license the therapy itself on a non-profit basis and without industry involvement, to make it more widely available to babies and children worldwide.
“We developed the treatments, saw the amazing results in the trial and then we hit this roadblock,” says Prof Claire Booth, from Gosh and University College London, who was a lead investigator in the trial. “We are seeing more and more companies pulling out of the field. So we had to find a way to get it to patients.”
The move comes amid concerns about the affordability of gene therapies, which could leave them out of reach for many patients. The spinal muscular atrophy drug The price of Zolgensma is £1.6 millionwhile the National Institute for Health and Care Excellence recently refused to approve NHS funding for Casgevya newly licensed gene editing therapy for sickle cell disease.
But, Booth said, these treatments “don’t literally cost £1m” and could cost a tenth of that under the approach Gosh hopes to pioneer.
The hospital plans to apply to the UK regulator, the Medicines and Healthcare Products Regulatory Agency, next year for its treatment for ADA-SCID, a devastating genetic condition that affects around one in 500,000 people, equivalent to one in three people born in England. every year. Children with the condition have no immune system and the condition can be fatal within the first two years of life if left untreated. Everyday activities such as going to school or playing with friends can lead to a dangerous infection.
The standard treatment involves either weekly injections of an enzyme or a bone marrow transplant, if a donor can be found. Both options require lifelong medication and carry risks of complications.
The gene therapy approach is a one-time treatment in which stem cells are harvested, genetically reprogrammed and reintroduced to the patient. “The cells go back into the patient, bed in the bone marrow and then grow a whole new working immune system that should last them for the rest of their lives,” Booth said.
Currently, the treatment can be offered to patients on a compassionate use basis, but “it’s not a sustainable way to do it”, Booth said. A license can make it the standard, approved treatment.
Booth and colleagues received £350,000 from medical charity LifeArc and Gosh’s charitable arm to prepare an application to regulators. The hope is that this will pave the way for a similar approach to bringing other gene therapies to market.
Dr Catriona Crombie, Head of Rare Diseases at LifeArc, said: “It is not acceptable for us to have proven treatments not reaching patients due to commercial challenges, and we are determined to drive change. Unfortunately, we know that this is not the only gene therapy drug for a rare disease that is abandoned or not developed for commercial reasons.
“We are incredibly pleased to be working with Gosh to see if this model can lay the foundation for an entirely new way of giving more people access to life-changing treatments. If successful, we hope it will be proof of concept that will then allow other gene therapies for rare genetic diseases to be made available.
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‘Let’s give these kids a chance’
The first hints that something was wrong weren’t alarming: baby Sarah had diaper rash, thrush and wasn’t gaining weight. “I tried to be relaxed and think every child has those things,” recalls her mother, Maria-Luiza Prioteasa. But when Sarah continued to lose weight at one month old and developed a chest infection, she was admitted to hospital for testing. A blood test revealed that Sarah had ADA-SCID, sometimes called “bubble boy syndrome,” which means she has no functioning immune system.
The standard treatment for the condition is a bone marrow transplant, but there was no matching donor on the register and neither Prioteasa nor Sarah’s father were compatible. “I know the feeling, as a parent, when you think everything is gone,” says Prioteasa. But at this point the family learned of a gene therapy trial at Gosh, which doctors hoped could offer a cure. “We signed the documents because it was the only option at the time,” says Prioteasa.
At just six months old, Sarah became one of the first babies in the world to receive the therapy, which involved removing her bone marrow cells, genetically reprogramming them in the laboratory and reintroducing them to her body. The treatment was successful and after six months Sarah was able to reduce her immune medication and for the first time since diagnosis was allowed to go out without a plastic cover over her pram. “I crossed the road if someone came to me,” says Prioteasa.
Sarah recently turned eight and is a happy, healthy, active child. “She is doing very well,” says Prioteasa. “She was in kindergarten, she goes to school, I’m not afraid of her catching things in the winter. I let her be like everyone else. I owe [Gosh] her life.”
However, other families she met through patient forums still live under the shadow of the disease. “I can see in other places they don’t have it. These children stay in the house, you cannot have a life as a child and a life as a parent,” she says. “There are many who wait ages to get treatment. It’s not fair. Let’s give these kids a chance.”
