PCSK9 Inhibitor Shows Positive Results in Statin-Intolerant Patients With High Cholesterol

A successful phase 3 drug trial for a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor achieved its co-primary endpoints for patients who suffer from high cholesterol and cannot tolerate statins.

The GAUSS-3 trial examined the safety, efficiency, and tolerability of evolocumab (Repatha), which is manufactured by Amgen. Researchers evaluated the mean percent reductions at weeks 22 and 24 from baseline in low-density lipoprotein cholesterol (LDL-C), and the percent reduction from baseline in LDL-C at week 24.

The results of the study showed that the mean percent reductions in LDL-C, compared with ezetimibe, were consistent with the results that were found in the phase 2 GAUSS-1 and phase 3 GAUSS-2, 12-week trials.

The human monoclonal antibody binds to PCSK9 and to inhibit it from binding to the LDL receptor (LDLR), which stops PCSK9-mediated LDLR degradation and allows LDLR to recycle back to the liver cell surface.

By inhibiting the binding of PCSK9 to LDLR, Repatha increases the number of LDLRs available to clear LDL from the blood, thereby lowering LDL-C levels.

"The positive results from the GAUSS-3 study contribute to the growing body of evidence supporting Repatha as an innovative treatment option for patients who have not been able to adequately lower their LDL cholesterol through diet and statins alone," said Executive Vice President at Amgen, Sean E. Harper, MD. "Many patients with high LDL cholesterol are unable to tolerate effective doses of statins, and the findings from the rigorously-designed GAUSS-3 study confirm the results in the previous GAUSS studies. We look forward to exploring these data further."

During the trial there were no new safety findings. The most common adverse events occurring in greater than 5% of patients in the Repatha group were, muscle spasms, fatigue, myalgia, nasopharyngitis, arthralgia, pain in extremity, headache, and back pain.