PCSK9-Hemmung mit Antikörpern: Die Resultate der Phase-III-Studienprogramme

The approval of PCSK9 inhibitors has led to a substantial increase of therapeutic options in the management of blood lipid levels. This is especially important for high-risk patients and patients with familiar hyperlipidemia, who cannot achieve adequate LDL-C lowering with other lipid lowering therapies. In the PROFICIO study program, the fully human anti-PSCK9 antibody evolocumab led to a significant reduction of LDL-C. Good tolerability and a significant reduction in LDL-C levels were maintained during long-term treatment. In addition, a reduction in cardiovascular events compared to standard therapy was noted. A significant reduction of LDL-C was also observed during the ODYSSEY study program with the fully human anti-PCSK9 antibody alirocumab. Combination therapy with statins or other lipid lowering treatment or monotherapy with both antibodies were well tolerated. A post hoc analysis of long-term data showed preliminary evidence for positive effects on cardiovascular risk. The data of the prospective randomised FOURIER study showed a significant reduction of the clinical outcomes. The ODYSSEY Outcomes study will provide further insights in the future. Bococizumab, a humanized anti-PCSK9 antibody similarly showed a significant benefit in high risk patients in SPIRE, but not in SPIRE 1 with low risk patients. However, the SPIRE-2 program was prematurely terminated. Because of undesired side effects.