Amgen has announced that the phase 3 GAUSS-2 ( Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects-2 ) trial evaluating Evolocumab in patients with high cholesterol who cannot tolerate statins met its co-primary endpoints: the percent reduction from baseline in low-density lipoprotein cholesterol ( LDL-C ) at week 12 and the mean percent reduction from baseline in LDL-C at weeks 10 and 12.
The mean percent reductions in LDL-C, compared to Ezetimibe ( Ezetrol, Zetia ) were consistent with results observed in the Phase 2 GAUSS study.
Evolocumab is an investigational fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 ( PCSK9 ), a protein that reduces the liver's ability to remove LDL-C from the blood.
The GAUSS-2 trial evaluated safety, tolerability and efficacy of Evolocumab in 307 patients with high cholesterol who could not tolerate effective doses of at least two different statins due to muscle-related side effects.
Patients were randomized to one of four treatment groups: subcutaneous Evolocumab 140 mg every two weeks and oral placebo daily; subcutaneous Evolocumab 420 mg monthly and oral placebo daily; subcutaneous placebo every two weeks and oral Ezetimibe 10 mg daily; or subcutaneous placebo monthly and oral Ezetimibe 10 mg daily.
Safety was generally balanced across treatment groups. The most common adverse events ( greater than 5% in Evolocumab combined group ) were headache ( 7.8% Evolocumab; 8.8% Ezetimibe ), myalgia ( 7.8% Evolocumab; 17.6% Ezetimibe ), pain in extremity ( 6.8% Evolocumab; 1.0% Ezetimibe ), and muscle spasms ( 6.3% Evolocumab; 3.9% Ezetimibe ).
The positive GAUSS-2 results suggest that Evolocumab may offer a new lipid-lowering treatment to meet an important medical need for high-risk patients who cannot tolerate effective doses of statins.
According to the Centers for Disease Control and Prevention ( CDC ), more than 71 million American adults have high LDL-cholesterol. Elevated LDL-cholesterol is recognized as a major risk factor for cardiovascular disease.
While statins are effective, it is estimated that 5 to 15% of patients cannot tolerate statins, primarily due to muscle-related side effects. ( Xagena )
Source: Amgen, 2014