Date: 2014-10-01
Type of
information: Publication of results in a medical journal
phase: 3
Announcement: publication of results in The Lancet
Company: Amgen (USA - CA)
Product: evolocumab
Action
mechanism:
- monoclonal antibody/RNAi/PCSK9 inhibitor. Evolocumab is a fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 is a protein that targets LDL receptors for degradation and thereby reduces the liver's ability to remove LDL-C, or "bad" cholesterol, from the blood. Evolocumab, being developed by Amgen scientists, is designed to bind to PCSK9 and inhibit PCSK9 from binding to LDL receptors on the liver surface. In the absence of PCSK9, there are more LDL receptors on the surface of the liver to remove LDL-C from the blood.
Disease: heterozygous familial hypercholesterolemia
Therapeutic
area: Cardiovascular diseases - Genetic diseases - Rare diseases
Country: Australia,Canada,France,Germany, Hong Kong, Netherlands, New Zealand, Norway, South Africa, Spain, Sweden, Switzerland, UK, USA
Trial
details:
- RUTHERFORD-2 (RedUction of LDL-C with PCSK9 InhibiTion in HEteRozygous Familial HyperchOlesteRolemia Disorder Study-2) is a Phase 3 randomized, multicenter, double-blind, placebo-controlled trial designed to evaluate the safety, tolerability and efficacy of evolocumab in 329 patients with HeFH and an LDL-C >100 mg/dL who were on a stable dose of statin therapy and lipid-lowering medication. Patients were randomized to one of four treatment groups to compare subcutaneous evolocumab (140 mg every two weeks or 420 mg monthly) with subcutaneous placebo (every two weeks or monthly). The co-primary endpoints were the percent reduction from baseline in LDL-C at week 12 and the mean percent reduction from baseline in LDL-C at weeks 10 and 12. Co-secondary efficacy endpoints included means at weeks 10 and 12 and at week 12 for the following: absolute change from baseline in LDL-C; LDL-C < 70 mg/dL; and the percentage change from baseline in non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), total cholesterol (TC)/HDL-C ratio, ApoB/apolipoprotein A1 (ApoA1) ratio, lipoprotein(a), triglycerides, HDL-C and very low-density lipoprotein cholesterol (VLDL-C). (NCT01763918)
Evolocumab phase III program, PROFICIO (Program to Reduce LDL-C and Cardiovascular Outcomes Following Inhibition of PCSK9 In Different POpulations), includes 13 trials, with a combined planned enrollment of more than 28,000 patients. The Phase 3 studies will evaluate evolocumab administered every two weeks and monthly in multiple patient populations, including in combination with statins in patients with hyperlipidemia (LAPLACE-2), in patients with hyperlipidemia who cannot tolerate statins (GAUSS-2), as a stand-alone treatment in patients with hyperlipidemia (MENDEL-2), and in patients whose elevated cholesterol is caused by genetic disorders called heterozygous (RUTHERFORD-2) and homozygous (TESLA and TAUSSIG) familial hypercholesterolemia.
- Five studies of evolocumab will provide long-term safety and efficacy data. These include FOURIER (Further Cardiovascular OUtcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk), which will assess whether treatment with evolocumab in combination with statin therapy compared to placebo and statin therapy reduces recurrent cardiovascular events in approximately 22,500 patients with cardiovascular disease, DESCARTES (Durable Effect of PCSK9 Antibody CompARed wiTh PlacEbo Study) in patients with hyperlipidemia at risk for cardiovascular disease, and GLAGOV (GLobal Assessment of Plaque ReGression with a PCSK9 AntibOdy as Measured by IntraVascular Ultrasound), which will determine the effect of evolocumab on coronary atherosclerosis in approximately 950 patients undergoing cardiac catheterization.
Latest
news:
- • On October 1, 2014, Amgen announced The Lancet published data from two Phase 3 studies, RUTHERFORD-2 and TESLA, that showed treatment with evolocumab resulted in a statistically significant reduction in LDL-C compared to placebo in patients with different types of familial hypercholesterolemia (FH). The RUTHERFORD-2 study evaluating 329 patients with heterozygous FH (HeFH) showed that adding subcutaneous evolocumab (140 mg every two weeks or 420 mg monthly) to a stable dose of statin and other lipid-lowering therapies significantly reduced mean LDL-C by 59-66 percent from baseline compared to placebo at week 12 and weeks 10 and 12 (p<0.001). At week 12, an LDL-C level of 70 mg/dL (1.8 mmol/L) was achieved by 68 percent of patients treated with evolocumab 140 mg every two weeks and by 63 percent of patients treated with evolocumab 420 mg monthly, versus 2 percent of patients in the placebo groups (p
- • On March 29, 2014, Amgen has announced new detailed data from three Phase 3 studies that showed treatment with its novel investigational cholesterol-lowering medication, evolocumab (AMG 145), resulted in a statistically significant reduction of 55-66 percent in low-density lipoprotein cholesterol (LDL-C) compared to placebo in patients with high cholesterol. Results from the three separate Phase 3 studies, MENDEL-2, DESCARTES and RUTHERFORD-2, were presented as Featured Clinical Research in a Special Session at the American College of Cardiology's 63rd Annual Scientific Session (ACC.14). The RUTHERFORD-2 study showed that in 329 HeFH patients on a stable dose of statin and other lipid-lowering therapies, treatment with subcutaneous evolocumab significantly reduced mean LDL-C by 59-66 percent from baseline compared to placebo (p<0.001). Data show the mean percent reduction from baseline in LDL-C at weeks 10 and 12 were 60 percent for evolocumab 140 mg every two weeks and 66 percent for evolocumab 420 mg monthly compared to placebo. At week 12, the percent reduction from baseline in LDL-C was 59 percent for evolocumab 140 mg every two weeks and 61 percent for evolocumab 420 mg monthly compared to placebo.
- The most common AEs (=2 percent in the combined evolocumab group) were nasopharyngitis (8.6 percent evolocumab; 4.6 percent placebo), headache (4.1 percent evolocumab; 3.7 percent placebo), contusion (i.e., bruise) (4.1 percent evolocumab; 0.9 percent placebo), back pain (3.6 percent evolocumab; 0.9 percent placebo), nausea (3.6 percent evolocumab; 0.9 percent placebo), influenza (3.2 percent evolocumab; 0 percent placebo), myalgia (2.7 percent evolocumab; 0 percent placebo) and pain in the extremity (2.3 percent evolocumab; 2.8 percent placebo).
Is
general: Yes
