A gene-therapy trial by London researchers has seen remarkable success in finding a long-term cure for hemophilia A. The trial, by researchers at Barts Health NHS (National Health Service) Trust and Queen Mary University of London, used gene therapy to inject one dose of a missing gene in patients with the condition, and the gene continued functioning in the body for more than a year.
This is the first successful gene therapy to treat the condition. Hemophilia is a hereditary genetic disorder, mostly affecting men, causing people to have low levels of clotting factor VIII, needed for their blood to clot. Lack of the protein factor results in excessive bleeding from even minor injuries and can cause internal bleeding, which is life-threatening.
To date, there is no permanent cure for hemophilia, and patients have to take multiple weekly injections of clotting factor VIII to prevent and control bleeding. “I’m very optimistic that we can deliver long-term treatment benefits,” said John Pasi, Haemophilia Centre director at Barts Health NHS Trust and lead author of the study published Saturday in the New England Journal of Medicine.
“To say that it’s going to be an absolute cure would be a bit rash, but I’m extremely optimistic that we will follow these patients and hopefully see great results continuing.”
Record success in trial
More than 400,000 people around the world are estimated to suffer from hemophilia A, which is six times as common as hemophilia B, according to an accompanying editorial. Type A sufferers lack factor VIII clotting protein, while those with type B lack factor IX. In the UK, where the study was conducted, around 2,000 people suffer from severe hemophilia A.
During the trial, 13 patients received high-dose injections containing a copy of the gene that in turn codes the missing clotting protein. The patients were followed for 19 months to monitor success. All 13 patients were off their treatment one year on, while 11 showed near-normal levels of the clotting protein and the remaining two showed stable levels, said Pasi.
The only side-effect Pasi said his team noticed was a sudden spike in liver enzymes, by up to three times. This did not result in external symptoms and eventually stabilized. “We’re trying to understand why [the spike] might happen but it’s something that’s fairly well recognized across gene therapy,” he adds.
Breakthrough in curing hemophilia
Treatiing people with hemophilia A is very expensive, and the patients themselves face numerous lifestyle hurdles. “The clotting factors are incredibly expensive, costing about £100,000 ($130,000) per patient per year, without ancillary care,” said Simon Waddington, reader in gene transfer technology at University College London, who was not involved in the trial.
“They inject the factors and of course, you have peaks and drops in the circulatory levels of the factors so they are at risk of bleeding through their joints when the levels drop out.” With gene therapy, he explained, a single injection could provide the steady levels needed, and be more cost-effective.
Jake Omer, a father of two, was diagnosed with hemophilia A when he was two years old and suffers from arthritis in his ankles because of repeated internal bleeding. Participation in the trial has dramatically changed his life. “I now have hope for my future. It is incredible to now hope that I can play with my kids, kick a ball around and climb trees well into my kids’ teenage yeaars and beyond,” he said in a statement.
Gene therapy has high success
“Gene therapy has now turned the corner completely in terms of showing incredible results in a variety of different early clinical trials,” said Waddington. “For this trial, it is delightful that such high levels [of success] have been achieved because factor VIII has always been considered a much tougher target using gene therapy… [because it is a] more difficult molecule to manipulate.”
Another common side-effect of gene therapy is an immune response to the injections that some patients have, he added. This can be countered using steroids or immune suppressants, to prevent the body from flushing the gene out.
Pasi regards durability as the big question in this trial the only other hemophilia trial on humans, done seven years ago, has continued to show stability, he said, which makes him hopeful. The team is in talks with BioMarin Pharmaceutical, which manufactured the injection for this study, for investment in larger facilities. They aim to expand to patients in Europe, the US, Africa and South America, with 60 new patients in the next trial.