First ever successful gene therapy for rare blood clotting disorder

Hundreds of haemophilia A patients in the UK could benefit from the first ever gene therapy for the condition.

A four year trial has shown that patients with the rare haemophilia A condition continue to show a positive and sustained response to gene therapy.

Haemophilia A affects the blood's ability to clot because patients don’t produce a key clotting protein called Factor 8. This leads to severe pain from joint bleeds, bruising and prolonged bleeding from wounds.

Usually an inherited condition, there are more than 2,000 severe haemophilia A patients in the UK. These patients have to be treated with Factor 8 injections three times a week or even more frequently.

Gene therapy has existed for around 15 years for haemophilia B in which Factor 9 is deficient. But haemophilia A has proved more difficult because the Factor 8 gene is very large in comparison to the Factor 9 gene. The missing protein clotting Factor 8 gene has to be inserted into a virus which is used as a vehicle to carry it after being injected into the patient’s blood as a single infusion. It then circulates to the patient’s liver and induces it to start producing the missing Factor 8.

Scientists have made this possible by truncating the Factor 8 gene so that only the much smaller active part is retained and it can fit into the virus.

This new gene therapy for haemophilia A has been tested at several hospitals in the UK, including Guy’s and St Thomas’ NHS Foundation Trust, and has shown very positive results.  One of the first patients to take part in the phase 1 trial is Shaun Busby at Guy’s and St Thomas’. He first received this treatment in February 2016.

The new 3-4 year follow-up data is ‘very impressive’ according to the principal investigator on the gene therapy trial at Guy’s and St Thomas’, consultant haematologist Dr Bella Madan.

Dr Madan said: “It has been extremely successful and beyond our wildest dreams. These are the first patients with haemophilia A to be treated with gene therapy.

“Our patient’s life has been transformed remarkably since receiving a single infusion of gene therapy in February 2016. He has infrequent bleeds, copes well with a very physically demanding job as an engineer. He is no longer dependent on three times a week injections that he was previously requiring, and needs Factor 8 injections only occasionally.”

Shaun Busby, 33, is a patient at Guy’s and St Thomas’ and an engineer from Tooting in south London.

“Living with it is very difficult because you are forever in and out of hospital clinics and appointments. As a child I lost time from school despite trying my best not to. During my adult life I have had severe problems with my knee and have required a knee replacement due to recurrent bleeds.

“It is mentally uplifting for me as I now don’t have to worry about all the things I used to. I have joint bleeds only occasionally and need Factor 8 injections much less frequently.

“I feel more alive after the trial and it has had a huge impact on my quality of life. I can also go away on holidays and go to music festivals without worrying too much about joint bleeds.  I have to pinch myself all the time – four years ago I was struggling – having bleeds and worrying about pain medication and Factor 8 injections.”

The latest results show that the thirteen patients in the study have achieved significant increase in Factor 8 levels such that they do not require regular Factor 8 injections.

Guy’s and St Thomas’ is currently conducting further tests on safety and effectiveness with a larger pool of participants through so called Phase 3 trials. The pharmaceutical firm pioneering the treatment is currently seeking regulatory approval from the European Medicines Agency.

An article on the trial called Multiyear Follow-up of AAV5-hFVIII-SQ Gene Therapy for Hemophilia A was published in the New England Journal of Medicine on 2 January 2020.