A new study led by Wolfgang Miesbach, published in Molecular Therapy – Methods and Clinical Development, explores AAV5 antibodies in haemophilia B gene therapy.

Recent research shows that nearly half of patients with haemophilia B had neutralizing antibodies (NAbs) at screening, with levels remaining stable over eight months, which is crucial for therapy planning.

The study, supported by CSL and led by Robert Klamroth and Sandra Le Quellec, emphasizes the importance of NAb screening in gene therapy planning.

While the presence of AAV5 NAbs isn't an absolute barrier to using etranacogene dezaparvovec, very high titers can reduce transduction efficiency, making NAb screening essential for determining eligibility.

NAb test results are consistent over several months, allowing screening up to eight months before gene therapy infusion, which offers greater clinical flexibility.

The study analyzed how AAV5 NAb levels behave over time in adults with haemophilia B, based on the HOPE-B phase 3 trial involving 67 patients across the US and Europe.

NAb positivity was more prevalent in patients aged 50 and above, with statistical significance (p=0.0065), indicating age-related differences.

There is a very strong correlation (r=0.96) between NAbs and IgG levels, with less than 5% of patients switching from negative to positive NAb status, and about 10% reverting from positive to negative.