First gene therapy for haemophilia A approved

The first gene therapy for haemophilia A has been approved for severe cases by the US Food and Drug Administration (FDA).

Haemophilia A is an X-linked heritable bleeding disorder that mainly affects boys and is caused by mutations in a gene called F8. These mutations inactivate F8's protein product, a molecule involved in blood clotting called Factor VIII, causing patients to bleed more easily and for longer when they are wounded.

'Most severe haemophilia A patients suffer recurrent break-through bleeding into joints despite treatment that ultimately leads to disability and chronic pain' said Professor Amit Nathwani, the leader of the team that developed the new therapy from University College London. 'The approval of Roctavian is an important and long-awaited advance that addresses the genetic cause of the condition.'

Roctavian was approved by the FDA for adults with specific severe forms of the disease and uses an adeno-associated virus (AAV) to insert DNA into patient cells that makes them produce functional Factor VIII.

BioMarin, the company that plans to sell the drug for $2.9 million per dose, showed in a Phase III clinical study of 112 patients that a single dose of Roctavian halved the frequency of bleeding incidents over three years.

However, the treatments effectiveness may decrease over time, and it cannot be administered multiple times or to patients with detectable antibodies against the AAV, as this could trigger a dangerous immune response.

While gene therapies have so far focused on conditions with few or no effective treatments, haemophilia A is often well managed by receiving infusions of blood clotting factors several times a week. However, this can cost $800,000 a year and is not adequate for all patients. It is hoped that Roctavian could address unmet clinical need and save money in the long term due to being single-use and long-lasting, although it remains to be seen if this will be the case.

'Today's approval represents an important advance in providing treatment options for patients with this bleeding disorder, and treatment with gene therapy may reduce the need for ongoing routine therapy' said Dr Peter Marks, the director of the FDA's Centre for Biologics Evaluation and Research.

The approval of Roctavian follows the recent approval of the first gene therapies for Duchenne's muscular dystrophy and dystrophic epidermolysis bullosa (see BioNews 1196 and 1191). The FDA has introduced an accelerated approval process for gene therapies for rare diseases (see BioNews 1184), and in the UK they are also approved under specialised terms as 'Advanced Therapy Medicinal Products'.