First gene therapy to treat severe haemophilia A

News 24/06/2022

EMA has recommended granting a conditional marketing authorisation in the European Union (EU) for Roctavian (valoctocogene roxaparvovec) for the treatment of severe haemophilia A in adults who do not have factor VIII inhibitors (auto-antibodies produced by the immune system which make factor VIII medicines less effective) and no antibodies to adeno-associated virus serotype 5 (AAV5).

Patients with haemophilia A cannot produce factor VIII (an essential protein required for blood to clot and stop bleeding); they are more prone to bleeding and have prolonged bleeding, e.g. after injury or surgery. Haemophilia A is a rare debilitating disease affecting approximately 0.7 in 10,000 people in the EU. It is life long and may be life threatening when bleeding occurs in the brain, the spinal cord or the gut.

Medicines currently authorised for treating haemophilia A mostly contain factor VIII, to replace the missing protein. Available treatments require one or more injections per week or per month and are lifelong. Therefore, there is an unmet medical need for new therapeutic approaches that might free patients from frequent injections.   

Roctavian is the first gene therapy to treat haemophilia A. The active substance in Roctavian, valoctocogene roxaparvovec, is based on a virus (adeno-associated virus or AAV) which has been modified to not cause disease in humans. The virus contains the gene for factor VIII; once given to a patient as a one-off infusion, it is expected to carry the factor-VIII gene into the liver cells, enabling them to produce the missing factor VIII. This helps the blood to clot more easily and prevents bleeding or reduces bleeding episodes. It is yet unknown how long the treatment effect from this single infusion will last in an individual patient. A sustained positive treatment effect of up to two years following a single infusion has been reported in approximately one hundred patients in the main study and up to five years in a few patients in a supportive trial conducted by the applicant. Longer-term follow-up tests may be required to verify a continued safe and effective response to the medicine.

EMA’s recommendation is based on the results of a Phase 3 single-arm (main study), non-randomised study in 134 male patients with haemophilia A without a history of factor VIII inhibitor and without detectable pre-existing antibodies to AAV5. Two years after the administration, efficacy data showed that the therapy significantly increased factor VIII activity levels in the majority of patients. Bleeding rates were reduced by 85% and most patients (128) no longer needed factor VIII replacement therapy.

Hepatotoxicity (liver damage), a common side effect due to immune reaction induced by these AAV-based gene therapies and characterised so far by an increase in the levels of a liver enzyme called alanine aminotransferase (ALT), has been reported with Roctavian. The condition can be treated successfully with corticosteroids. Other common side effects include headache, joint pain and nausea.

Patients treated with Roctavian will be monitored for 15 years, to ensure the long-term efficacy and safety of this gene therapy.

Roctavian was supported through EMA's PRIority MEdicines (PRIME) scheme, which provides early and enhanced scientific and regulatory support to medicines that have a particular potential to address patients' unmet medical needs.

In its overall assessment of the available data, the Committee for Advanced Therapies (CAT), EMA's expert committee for cell- and gene-based medicines, found that the benefits of Roctavian outweighed the possible risks in patients with haemophilia A.

The CHMP, EMA’s human medicines committee, agreed with the CAT’s assessment and positive opinion, and recommended approval of this medicine.

The opinion adopted by the CHMP is an intermediary step on Roctavian’s path to patient access. The opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorisation. Once a marketing authorisation has been granted, decisions about price and reimbursement will take place at the level of each Member State, taking into account the potential role or use of this medicine in the context of the national health system of that country.


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