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New Drugs Online Report for evolocumab
Information
Generic Name:
evolocumab 
Trade Name:  
Synonym: AMG 145 
Entry Type: New molecular entity  
 
Developmental Status
UK: Phase III Clinical Trials 
EU: Phase III Clinical Trials 
US: Pre-registration (Filed) 
UK launch Plans: Available only to registered users
Actual UK launch date:  
Comments
Aug 14: Biologics License Application (BLA) submitted to US FDA for evolocumab, seeking approval for the treatment of high cholesterol. The BLA contains data from approximately 6,800 patients, including>4,500 patients with high cholesterol in 10 Phase 3 trials. The Phase 3 studies evaluated the safety and efficacy of evolocumab in patients with elevated cholesterol on statins with or without other lipid-lowering therapies; patients who cannot tolerate statins; patients with heterozygous familial hypercholesterolemia (HeFH); and patients with homozygous familial hypercholesterolemia (HoFH), a rare and serious genetic disorder.[6] 
29/08/2014 09:10:24
 
Trial or other data
Apr 14: In the RUTHERFORD-2 study in 329 HeFH patients on a stable dose of statin and other lipid-lowering therapies , the mean % reduction from baseline in LDL-C at weeks 10 and 12 were 60% for evolocumab 140 mg every two weeks and 66% for evolocumab 420 mg monthly vs placebo (p<0.001). [5] 
02/04/2014 11:52:40
Jan 14: Results reported from the PIII RUTHERFORD-2 (RedUction of LDL-C with PCSK9 InhibiTion in HEteRozygous Familial HyperchOlesteRolemia Disorder Study-2) trial. The study met its co-primary endpoints: % reduction from baseline in LDL-C at week 12 and mean % reduction from baseline in LDL-C at weeks 10 and 12. RUTHERFORD-2 trial evaluated safety, tolerability and efficacy of evolocumab in 329 HeFH patients on a stable dose of statin and other lipid-lowering therapies. Patients were randomized to 1 of 4 treatment groups: evolocumab (140mg every two weeks or 420mg monthly) with subcutaneous placebo (every two weeks or monthly). Safety was balanced across treatment groups except for the following most common AEs (≥ 2% in evolocumab combined group and ≥ 2% vs placebo): nasopharyngitis (8.6% evolocumab vs 4.6% placebo), contusion (4.1 vs 0.9%), back pain (3.6 vs 0.9%), nausea (3.6 vs 0.9%), influenza (3.2 vs 0%), and myalgia (2.7 vs 0%). In a separate PIII study that enrolled 164 patients with high cholesterol on statin therapy, 95% of patients were able to self-administer at least one full home administration of evolocumab 420mg subcutaneously by one injection with an automated mini-doser or by three injections with a standard spring-based autoinjector [4].  
04/02/2014 18:03:43
Jan 13: NCT01763918 (RUTHERFORD-2) is a PIII double-blind, randomized, placebo-controlled, multicentre study to evaluate safety, tolerability and efficacy of AMG 145 on LDL-C in 300 subjects with heterozygous familial hypercholesterolemia. The primary outcome is % change from baseline in LDL-C at 12 weeks. The study starts Feb 13 and is due to complete Dec 13 [3]. 
10/01/2013 11:34:43
Nov 12: Results from the RUTHERFORD study released; a double-blind, placebo-controlled phase II RCT that evaluated AMG 145, dosed subcutaneously Q4W, in 168 pts with an LDL-C >100 mg/dL who were on a stable dose of statin, with or without ezetimibe. Pts were randomized to three treatment groups: AMG 145 at 350 mg, AMG 145 at 420 mg or placebo administered subcutaneously every four weeks. The primary endpoint was percentage change from baseline in LDL-C, measured by preparative ultracentrifugation, at week 12. Treatment with AMG 145 every four weeks (Q4W) resulted in a significant LDL-C decrease versus placebo in HeFH patients on lipid-lowering therapy (statins with or without ezetimibe). At week 12, LDL-C reduction, measured by preparative ultracentrifugation, was 43% and 55% with AMG 145 350 mg and 420 mg, respectively, compared to a 1% increase with placebo (p<0.001 for both dose groups). At week 12, treatment with AMG 145 350 mg and 420 mg Q4W resulted in 70% and 89% of pts reaching LDL-C levels of <100 mg/dL and 44% and 65% achieving <70 mg/dL, respectively, compared to 2% and 0% of placebo subjects, respectively. Favorable reductions in total cholesterol, non-HDL-C, Lp(a) and ApoB were consistent with the reductions in LDL-C [2]. 
07/11/2012 10:40:40
   
References  
Available only to registered users
Category
BNF Category:
Lipid-regulating drugs (02.12)
Pharmacology: Fully human monoclonal antibody to Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9), a negative regulator of the LDL receptor.  
Epidemiology:  
Indication: Heterozygous familial hypercholesterolaemia 
 
Method(s) of Administration
Subcutaneous 
 
Company Information
Name: Amgen 
US Name: Amgen 
 
NICE Information
In timetable: No  
When: