EMA has recommended granting a conditional marketing authorisation in the European Union (EU) for Durveqtix (fidanacogene elaparvovec) to treat severe and moderately severe haemophilia B in adults who do not have factor IX inhibitors (auto-antibodies produced by the immune system against factor IX replacement medicines) and who have no detectable antibodies to variant adeno-associated virus serotype Rh74 (AAVRh74var).
Haemophilia B is a rare inherited bleeding disorder. The condition is caused by the lack of coagulation factor IX, a protein needed to produce blood clots to stop bleeding and seal wounds. Without that protein, patients with haemophilia B bruise easily and bleed more frequently and for longer periods of time. It can lead to serious complications, such as bleeding in joints, muscles or internal organs, including the brain.
Most of the currently authorised medicines for haemophilia B require frequent and lifelong intravenous infusions to prevent or treat bleeding. Patients need more new treatments that provide sustained bleed protection, reduce frequency of infusions and improve their quality of life.
Durveqtix is a gene therapy delivered as a single infusion that aims at enabling the body to produce factor IX itself and prevent and control bleeding.
The recommendation is based on the results of an ongoing single-arm, open-label, phase 3 trial in 45 adult male patients with moderately severe or severe haemophilia B who tested negative for neutralising antibody to AAVRh74var and received a single intravenous infusion of fidanacogene elaparvovec. The study compares the annualised bleeding rate (ABR), which included both treated and untreated bleeding events, in participants treated with gene therapy versus the period when they were treated with routine factor IX prophylaxis regimen, administered as part of standard care, in a lead-in study.
Results show that Durveqtix substantially reduces the frequency of bleeding compared to standard care. ABR was 1.44 for fidanacogene elaparvovec versus 4.50 for prophylaxis treatment. Over time, 60% of patients remained without a bleeding event in the individual observation period (ranging from two to up to four years) compared to 29% of patients when they received routine prophylaxis treatments during the lead-in period. The consumption of prophylactic factor IX was reduced by 92.4% after treatment with Durveqtix.
Patients treated with Durveqtix will be followed up for 15 years, including six years in the pivotal clinical trial and an additional nine years as part of a separate study to monitor the long-term efficacy and safety of this gene therapy.
The most common side effect is an increase in the levels of liver enzymes (transaminases). The condition can be treated with corticosteroids. Other common side effects include headache and flu-like symptoms, increased levels of creatinine (a marker for impaired kidney function) and lactate dehydrogenase (a marker for tissue damage). Patients should be monitored for infusion-related reactions.
Durveqtix 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 Durveqtix outweighed the possible risks in patients with haemophilia B. 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 Durveqtix’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.
Notes
1. The applicant for Durveqtix is Pfizer Europe MA EEIG.
2. Durveqtix was granted eligibility to PRIME on 23 February 2017 for the treatment of severe haemophilia B.