LOS ANGELES — When administered every 4 weeks, AMG 145 provided rapid and significant reductions to LDL and was well tolerated by patients with heterozygous familial hypercholesterolemia, researchers reported here.
Results from the phase 2 RUTHERFORD trial demonstrated LDL reductions of up to 56% with AMG 145 (Amgen, Inc.) in combination with statin therapy, with or without ezetimibe (Zetia, Merck), for patients with heterozygous familial hypercholesterolemia. At 12 weeks, LDL reduction, as measured by preparative ultracentrifugation, was 43% and 55% with AMG 145 in the 350-mg and 420-mg doses, as compared with a 1% increase with placebo (P<.001 for both dose groups), according to a press release.
The target goal of LDL <100 mg/dL was achieved by 70% of patients assigned AMG 145 350-mg and 89% assigned AMG 145 420 mg. Further, 44% and 65% achieved LDL <70 mg/dL, respectively, compared with 2% and 0% of patients assigned placebo in the same doses.
“Virtually all patients had a robust response to AMG 145,” Frederick Raal, MD, PhD, from the carbohydrate and lipid metabolism research unit at the University of Witwatersrand, Johannesburg, South Africa, said during a presentation at the American Heart Association Scientific Sessions 2012.
Favorable reductions in total cholesterol, non-HDL, Lp(a) and apolipoprotein B were consistent with reductions in LDL.
The most common treatment-emergent adverse events among patients assigned AMG 145 were nasopharyngitis, pain at the injection site and headache.
“These results suggest that AMG 145 may offer a new effective treatment to further reduce LDL in heterozygous familial hypercholesterolemia patients unable to achieve optimal LDL targets on current medications,” Raal said.
RUTHERFORD was a 12-week, randomized, double blind, placebo-controlled trial designed to examine the efficacy, safety and tolerability of AMG 145. Researchers recruited 167 patients (mean age, 50 years; 53% men) with heterozygous familial hypercholesterolemia with LDL >100 mg/dL who were on a stable dose of statin, alone or with ezetimibe. Patients were randomly assigned to three treatment groups: subcutaneous AMG 145 at 350 mg (n=55); AMG 145 at 420 mg (n=56); or placebo (n=56) every 4 weeks. – by Samantha Costa
For more information:
Raal F. Late-breaking clinical trials: Novel treatments for managing lipid disorders. Presented at: the American Heart Association Scientific Sessions; Nov. 3-7, 2012; Los Angeles.
Disclosure: Raal reports consulting fees from Amgen and Sanofi related to PCSK9 inhibitors, and his institution has received research funding related to PCSK9 inhibitor clinical trials from Amgen and Sanofi.