Results of the clinical-trial program with the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor bococizumab (Pfizer), including final data from the major outcome trials SPIRE 1 and 2, show that antidrug antibodies developed in a large proportion of patients and significantly attenuated the LDL-lowering effect[1,2].
But the drug had no effect on cardiovascular events in SPIRE-1 (HR 0.99, P=0.94), which included patients with lower LDL levels at baseline (>70 mg/dL) who were followed for a shorter duration (median 7 months).
Lead investigator of the SPIRE 1 and 2 studies and lead author of both papers on bococizumab, Dr Paul Ridker (Harvard Medical School, Boston, MA) commented to heartwire from Medscape: "Despite antidrug antibody development, bococizumab nonetheless significantly reduced vascular events by 21% among those with higher risk and higher LDL levels.
Because the bococizumab data are being published we wanted to get our data on alirocumab out there too so people can see immunogenicity is not necessarily such a big problem with the other drugs." He and his colleagues report data from 10 trials with alirocumab in a total of 4747 patients (3039 who received active drug), in which antidrug antibodies were observed in 5.1% of alirocumab patients vs 1.0% of control patients.
Commenting on the studies for heartwire , Dr Jeffrey S Berger (New York University School of Medicine, NY) said: "In light of the data demonstrating antidrug antibody formation with bococizumab and its mitigating effect on the reduction of LDL-cholesterol levels, the alirocumab data are timely and important and are certainly reassuring." He added, however, that "these data are derived from small populations with antidrug antibodies, and thus caution needs to be applied.