Drugs Xagena
The phase 3 GAUSS-3 ( Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects-3 ) trial evaluating Evolocumab ( Repatha ) in patients with high cholesterol who cannot tolerate statins met its co-primary endpoints: mean percent reductions from baseline in low-density lipoprotein cholesterol ( LDL-C ) at weeks 22 and 24, and the percent reduction from baseline in LDL-C at week 24.
The mean percent reductions in LDL cholesterol, compared to Ezetimibe, were consistent with results observed in the 12-week phase 2 GAUSS-1 and phase 3 GAUSS-2 trials.
GAUSS-3 is a three-part trial that is evaluating the safety, tolerability and efficacy of Evolocumab, an injectable proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) inhibitor, in patients with high cholesterol who could not tolerate statins due to muscle-related side effects ( MRSE ).
The active-controlled part of the trial evaluated the effect of 24 weeks of treatment with Evolocumab compared to Ezetimibe on percent change from baseline in LDL cholesterol.
In the GAUSS-3 trial there were no new safety findings. The most common adverse events that occurred in greater than 5% of patients in the Evolocumab group were myalgia, nasopharyngitis, muscle spasms, arthralgia, pain in extremity, fatigue, headache and back pain.
Evolocumab is a human monoclonal antibody that inhibits PCSK9. Evolocumab binds to PCSK9 and inhibits circulating PCSK9 from binding to the low-density lipoprotein ( LDL ) receptor ( LDLR ), preventing PCSK9-mediated LDLR degradation and permitting LDLR to recycle back to the liver cell surface.
By inhibiting the binding of PCSK9 to LDLR, Evolocumab increases the number of LDLRs available to clear LDL from the blood, thereby lowering LDL cholesterol levels.
GLAGOV, the intravascular ultrasound study, is underway to determine the effect of Evolocumab on coronary atherosclerosis in approximately 950 patients undergoing cardiac catheterization to test the hypothesis of robust LDL cholesterol reduction leading to a reduction or a change in the build-up of plaque in the arteries.
The FOURIER outcomes trial is designed to evaluate whether treatment with Evolocumab in combination with statin therapy, compared to placebo plus statin therapy, reduces the risk of cardiovascular events in patients with high cholesterol and clinically evident cardiovascular disease, and completed patient enrollment in June 2015. ( Xagena )
Source: Amgen, 2016
XagenaMedicine_2016
