When Great Ormond Street hospital (Gosh) published the results of its gene therapy trial for “bubble baby” syndrome it was hailed as a medical breakthrough. The treatment 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 had been dropped by the pharmaceutical company that planned to bring it to market.
Now, Gosh is taking the unprecedented step of attempting to license the therapy itself on a non-profit basis and without industry involvement, in order to make it more widely available to babies and children worldwide.
“We’ve been developing the treatments, seeing the amazing results in trial and then we hit this roadblock,” said Prof Claire Booth, of Gosh and University College London, who was a principal investigator on the trial. “We’re seeing more and more companies pulling out of the field. So we needed to find a way to get it to patients.”
The move comes amid concern about the affordability of gene therapies, which could leave them out of reach for many patients. The spinal muscular atrophy drug Zolgensma is priced at £1.6m, while the National Institute for Health and Care Excellence recently declined to approve NHS funding for Casgevy, a newly licensed gene editing therapy for sickle cell disease.
But, said Booth, these treatments “don’t literally cost £1m” and could cost one-tenth of this under the approach Gosh is hoping to pioneer.
The hospital plans to apply next year to the UK regulator, the Medicines and Healthcare products Regulatory Agency, for its treatment for ADA-SCID, a devastating genetic condition that affects about one in every 500,000 people, equivalent to one to three people born in England each 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-off treatment in which stem cells are harvested, genetically reprogrammed and reintroduced to the patient. “The cells go back into the patient, bed into the bone marrow and then grow a whole new working immune system that should last them for the rest of their life,” said Booth.
Currently the treatment can be offered to patients on a compassionate use basis, but “that’s not a sustainable way to do it”, said Booth. A licence could make it the standard, approved treatment.
Booth and colleagues have received £350,000 from the 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, the head of rare disease at LifeArc, said: “It is not acceptable to us that there are proven treatments failing to reach 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 being dropped or not developed for commercial reasons.
“We are incredibly pleased to partner with Gosh to see if this model could lay the foundations for an entirely new way of giving more people access to life-changing treatments. If successful, we hope that this might be a proof of concept that would then allow other gene therapies to be made available for rare genetic diseases.”
‘Let’s give these children a chance’
The first hints that something was wrong were not alarming: baby Sarah had nappy rash, thrush and was not gaining weight. “I tried to be relaxed thinking every child has those things,” recalls her mother, Maria-Luiza Prioteasa. But when, at a month old, Sarah was still losing weight and had developed a chest infection, she was admitted to hospital for testing. A blood test revealed Sarah had ADA-SCID, sometimes called “bubble boy syndrome”, meaning she had no working 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 provide a cure. “We signed the papers because it was the only option at the time,” Prioteasa says.
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 lab, and reintroducing them to her body. The treatment was successful and after six months Sarah was able to reduce her immune medication and was allowed to go out for the first time since diagnosis without having a plastic cover over her pram. “I used to cross the road if someone was coming towards me,” says Prioteasa.
Sarah recently turned eight and is a happy, healthy, active child. “She’s doing really well,” says Prioteasa. “She’s been to nursery, 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 has met through patient forums still live under the shadow of the illness. “I can see in other places they don’t have this. These children stay in the house, you can’t have a life as a child and a life as a parent,” she says. “There are plenty who wait ages to get treatment. It’s not fair. Let’s give these children a chance.”
