Gene therapy transforms lives for people with haemophilia A

Blood samples

“A normal life.” That, in the words of a clinical trial patient, is what a world-first gene therapy for severe haemophilia A can offer. ROCTAVIAN received marketing approval in Europe in 2022 and US FDA approval in 2023 and is now available to patients commercially. ROCTAVIAN (valoctocogene roxaparvovec) is a ‘one and done’ treatment approach: patients who previously needed regular protein injections to manage the bleeding disorder are experiencing life-changing benefits.

Taking on the challenge

The technology was licensed by UCLB to BioMarin Pharmaceuticals Inc in 2013 using research from Professor Amit Nathwani and his team at UCL and St. Jude Children’s Research Hospital. They published a pivotal study in 2011 reporting the first clear evidence of successful gene therapy for haemophilia B. For Amit, tackling haemophilia A was the natural next step. But this posed some challenges, as he explains:

“Haemophilia A is caused by a deficiency of clotting factor VIII. The F8 gene is very complicated, it’s larger than the gene for haemophilia B, so we had to do quite a bit of engineering to get the viral vector to the right size. The factor VIII protein is also expressed at much lower levels, so there was a challenge of how to increase expression.”

Part of the answer turned out to be a process called ‘codon optimisation’ whereby the researchers changed some of the gene’s ‘code’ to replicate that of proteins which are synthesised at high levels in the liver. Once injected, the virus delivers the recombinant F8 gene to several tissues. Because the promoter is liver-specific, the factor VIII protein is only synthesised in liver cells, then released back into the bloodstream. The result was a tenfold increase in factor VIII expression – enough to almost eliminate the risk of bleeding in patients.

A model for industry-academic collaboration

It was also enough to interest BioMarin, who opened discussions about licensing the technology. Richard Fagan is UCLB’s Director of BioPharm, and led on the licensing deal.

“BioMarin didn’t have experience in gene therapy at the outset. But they’ve been great to work with and very collaborative. In ten years, they’ve taken this therapy all the way through clinical development to marketing authorisation. They’ve run the largest clinical trials for a gene therapy for the treatment of haemophilia A in the world. So it’s a great example of an industry-academic partnership which has delivered real patient benefit.”

Having experienced an alternative commercialisation model as founder of gene therapy spinout Freeline Therapeutics, Amit reflects that each has its benefits:

“Licensing is great for my mental health because I throw it over the wall, and someone else does the work while I watch from the sidelines. But it does mean you have less influence over the process.”

He is grateful to BioMarin, who he says have fostered an open and respectful long-term relationship:

“I’m very proud of the fact that we’ve maintained a good, collaborative relationship with BioMarin for almost 10 years. This is a company that really moved the [gene therapy] field forward in a substantial manner and continues to invest in it. We had a meeting a couple of weeks ago on other research areas, and it’s refreshing to see how much effort they’re putting into getting this right and getting it better.”

A lifeline for patients around the world

The relationship with BioMarin will be key if Amit is to realise his ultimate ambition for Roctavian, to make it available to everyone in the world who needs it. He is driven by the potentially transformative impact on patients’ lives:

“With the standard of care treatment (FVIII concentrates), patients for example who were going to take part in physical activity would have to inject themselves with an additional dose. Whereas with gene therapy, they don’t even think about it anymore. They just go out and run or play.”

Life-changing for patients in high-income countries, gene therapy could be life-saving for people without access to ongoing treatment. Around 80% of haemophilia cases are among patients in the developing world, and many will die young.

“We can give somebody a vaccine against smallpox and that will protect them for the rest of their lives. And that’s what I wanted to do for the inherited diseases.”

Amit Nathwani


Gene therapies currently come with a hefty price tag. Although over the long term they offer cost-savings over the current standard of care, they remain out of reach for low- and middle-income countries.

“With BioMarin’s support, we’re exploring an opportunity to evaluate haemophilia gene therapy in patients in Uganda, which is where I was born. So I’m very excited about that. And if we can get this programme to work we’ll continue spreading it across the world.”

It’s a quest that, if fulfilled, could see many more people receive the gift of a “normal life”.

Learn more about the impact of this gene therapy. Hear from Professor Amit Nathwani, Richard Fagan, and a patient who has benefitted from the treatment.

Discover more, listen to Professor Amit Nathwani's interview in Episode 13 of the UCLB Big Talks on Big Impacts podcast series.