‘One-shot’ therapy for haemophilia A developed in UCL gets FDA approval

30 June 2023

Blood samples

A gene therapy drug, developed from research at UCL and St Jude Children’s Research Hospital, has been licensed for use in the United States.

Roctavian, which already has approval for use in Europe, is now cleared for use by the US Food and Drug Agency (FDA).

It means that thousands of US patients with a severe form of the blood clotting disease are now potentially eligible for the one-off treatment that corrects its genetic cause.

Access to the US market increases hopes of a wider rollout of the therapy for haemophilia A patients around the world.

The ‘one-shot’ gene therapy can eliminate the need for injections and is potentially curative.

Roctavian is based on technology licensed by UCL’s commercial subsidiary, UCLB, to BioMarin Pharmaceutical Inc based on research from Professor Amit Nathwani and his team at the UCL Cancer Institute.

Prof Nathwani pioneered a successful gene therapy for haemophilia B, but adapting the technology for use to treat haemophilia A required several further key innovations to the gene therapy which works by using deactivated viruses (viral vectors) to deliver the modified genes.

“Haemophilia A is caused by a deficiency of clotting factor VIII (factor 8). The factor 8 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,” Prof Nathwani explained.

“The factor VIII protein is also expressed at much lower levels, so there was a challenge of how to increase expression.”

Meeting that challenge led to the development of a much smaller codon optimised factor 8 gene which when delivered to the liver by the virus harnessed the liver’s ability to produce clotting proteins in sufficient quantities.

Gaining US approval crowns a 10-year collaboration overseen by UCLB between Prof Nathwani and BioMarin, Biomarin licensed the technology and conducted clinical trials which led to the marketing authorisation in Europe and now the USA.

Richard Fagan is UCLB’s Director of BioPharm, and led on the licensing deal. He said:

“This news is a great example of industry and academic collaboration delivering real patient benefit. Roctavian, a one-time therapy, is a historic achievement, based on decades of research by Professor Amit Nathwani, his team, and scientific colleagues in the USA: first licensed by UCLB to the biotech company, BioMarin in 2013.”

Anne Lane, CEO, UCLB added: “I’m delighted that Roctavian, a gene therapy developed at UCL by Professor Amit Nathwani and his team, and licensed to BioMarin via UCLB, has today received FDA approval for the treatment of severe haemophilia A. The therapy has already been approved for use in Europe. This is a great step forward in the treatment of this disease and should bring significant benefit to patients. This development also demonstrates the enormous role research commercialisation and knowledge transfer has to play in addressing the global challenges we all share.”

Professor Nathwani said: “It is humbling to be involved in the creation of the first gene therapy for patients with severe haemophilia A. Current treatment is effective but highly demanding requiring regular lifelong injections. Most severe haemophilia A patients suffer recurrent break-through bleeding into joints despite treatment that ultimately leads to disability and chronic pain. The approval of Roctavian, is an important and long-awaited advance that addresses the genetic cause of the condition. Roctavian is a one-time gene therapy that offers patients long term protection from bleeds and avoids the burden of regular infusions.”