Antidrug antibodies against PCSK9 antibody did not affect efficacy and safety
Antidrug Antibodies in Patients Treated with Alirocumab
Letter to the editorLiterature - Roth EM, Goldberg AC, Catapano AL, et al. - NEJM 2017, Epub ahead of print
Important positive outcome data of the FOURIER trial, in which the fully human PCSK9 antibody evolocumab had been used, have just been published . On the other hand, clinical development of a second murine-derived PCSK9 antibody, bococizumab, had been discontinued due to immunogenicity . Also alirocumab, another PCSK9 antibody but also fully human, provoked immunogenicity at very low rates in the ODYSSEY trials.
To assess the potential effect of antidrug antibodies against alirocumab on efficacy – in terms of LDL-lowering – and safety, antidrug antibody levels were evaluated in 4747 patients of 10 ODYSSEY trials and related to these parameters.
- 5.1% of alirocumab-treated patients and 1.0% of control patients presented with antidrug antibodies. This presence was persistent (≥12 weeks in at least 2 consequent samples) in 1.4% and 0.2% of patients, respectively.
- Antidrug antibodies did not interfere with efficacy, as comparable reductions in LDL-c levels were maintained over the course of the studies, regardless of antidrug antibody levels. For patients treated with 150 mg every 2 weeks, the least squares (LS) mean LDL-c level at 78 weeks was 52.2 mg/dL (95% CI 50.0-54.3) in patients that did not develop antidrug antibodies, 58.6 mg/dL (95% CI 47.3-69.9, P=0.2752) for those who had transient antidrug antibodies and 60.1 mg/dL (95% CI 41.9-78.2, P=0.3981) for those who had persistent antidrug antibodies, in which P corresponds to the comparison with the no antidrug antibody group. These numbers were 65.3 (95% CI 61.8-68.9), 56.2 (95% CI 44.1-68.3, P=0.1414) and 65.7 mg/dL (95% CI 47.0-84.5, P=0.9677) respectively, for patients who received 75 mg alirocumab every 2 weeks with possible dose increase to 150 mg.
- Regarding safety, no enhanced frequency of adverse events were observed in patients with or without antidrug antibodies (any treatment-emergent adverse event 79.7, 80.6 and 77.3% for no, transient and persistent), although injection-site reactions were more frequent among patients with antidrug antibodies (11.6% for transient and 15.9% for persistent) compared to without (5.9%).
Although antidrug antibodies were present in some patients treated with alirocumab, this did not affect the magnitude and duration of LDL-lowering. However, it should be noted that the number of patients with immunogenicity was very small.