During the discussion, the expert panel raised concerns about the Adnectin molecule's immunogenicity, drawing parallels with a previous case involving a humanized monoclonal antibody. Additional questions were asked about the program's size and scope, including patient numbers and therapy duration. The presenter Dr Klug, responded that the program was substantial, citing a study presented at ESC and published in the European Heart Journal involving familial hypercholesterolemic patients, which showed no evidence of anti-drug or neutralizing antibodies. A third trial in the high-risk group, yet to be presented, also indicated no increase in such antibodies, aligning with phase two study findings.

A question was also raised by the panel expert regarding the ongoing long-term extension to continue observing the development. Dr Klug stated that following the trial, a one-year ongoing longitudinal study was conducted, which was open-label, with all patients placed on Lerodalcibep, and they were monitored for similar antibodies. The panel expert inquired about the median reduction in free LDL, noting a difference compared to the median of 96%. Variability in LDL reduction was mentioned, with a request for information on standard deviations and consideration of waterfall plots to assess consistency. Dr Klug responded that a waterfall plot was available, showing that nearly 70% of patients experienced a reduction in LDL cholesterol of more than 50%. He emphasized that the reduction in LDL cholesterol was consistent in the trial, with a reminder of factors such as PCSK9 levels potentially affecting LDL lowering capacity.

The final comment was added by the panel expert, emphasizing the challenge of access and dealing with prior authorizations for monoclonals and an sRNA, despite their excellent efficacy. It was expressed that having an oral agent available would be beneficial, allowing for easier prescription and access for patients. The hope is for future improvements in accessibility for these drugs, as current processes are still cumbersome.

American College of Cardiology (ACC) Congress 2024, 6th April – 8th April 2024, Atlanta, Georgia, USA