PMID- 26757788
OWN - NLM
STAT- MEDLINE
DCOM- 20180410
LR  - 20220318
IS  - 1522-9645 (Electronic)
IS  - 0195-668X (Print)
IS  - 0195-668X (Linking)
VI  - 37
IP  - 17
DP  - 2016 May 1
TI  - Safety and efficacy of LY3015014, a monoclonal antibody to proprotein convertase 
      subtilisin/kexin type 9 (PCSK9): a randomized, placebo-controlled Phase 2 study.
PG  - 1360-9
LID - 10.1093/eurheartj/ehv707 [doi]
AB  - AIMS: The objective of this study was to evaluate the efficacy, safety, and 
      tolerability of LY3015014 (LY), a neutralizing antibody of proprotein convertase 
      subtilisin/kexin type 9 (PCSK9), administered every 4 or 8 weeks in patients with 
      primary hypercholesterolaemia, when added to a background of standard-of-care 
      lipid-lowering therapy, including statins. METHODS AND RESULTS: Double-blind, 
      placebo-controlled trial randomized 527 patients with primary 
      hypercholesterolaemia from June 2013 to January 2014 at 61 community and academic 
      centres in North America, Europe, and Japan. Patients were randomized to 
      subcutaneous injections of LY 20, 120, or 300 mg every 4 weeks (Q4W); 100 or 300 
      mg every 8 weeks (Q8W) alternating with placebo Q4W; or placebo Q4W. The primary 
      endpoint was percentage change from baseline in low-density lipoprotein 
      cholesterol (LDL-C) by beta quantification at Week 16. The mean baseline LDL-C by 
      beta quantification was 136.3 (SD, 45.0)mg/dL. LY3015014 dose-dependently 
      decreased LDL-C, with a maximal reduction of 50.5% with 300 mg LY Q4W and 37.1% 
      with 300 mg LY Q8W compared with a 7.6% increase with placebo maintained at the 
      end of the dosing interval. There were no treatment-related serious adverse 
      events (AEs). The most common AE terms (>10% of any treatment group) reported 
      more frequently with LY compared with placebo were injection site (IS) pain and 
      IS erythema. No liver or muscle safety issues emerged. CONCLUSIONS: LY3015014 
      dosed every 4 or 8 weeks, resulted in robust and durable reductions in LDL-C. No 
      clinically relevant safety issues emerged with the administration of LY. The 
      long-term effects on cardiovascular outcomes require further investigation.
CI  - (c) The Author 2016. Published by Oxford University Press on behalf of the European 
      Society of Cardiology.
FAU - Kastelein, John J P
AU  - Kastelein JJ
AD  - Department of Vascular Medicine, Academic Medical Center of the University of 
      Amsterdam, Meibergdreef 9, Room F4-159.2, 1105 AZ Amsterdam, The Netherlands 
      J.J.Kastelein@amc.uva.nl juliesherman@lilly.com.
FAU - Nissen, Steven E
AU  - Nissen SE
AD  - Cleveland Clinic Heart and Vascular Institute, Cleveland, OH, USA.
FAU - Rader, Daniel J
AU  - Rader DJ
AD  - University of Pennsylvania, Philadelphia, PA, USA.
FAU - Hovingh, G Kees
AU  - Hovingh GK
AD  - Department of Vascular Medicine, Academic Medical Center of the University of 
      Amsterdam, Meibergdreef 9, Room F4-159.2, 1105 AZ Amsterdam, The Netherlands.
FAU - Wang, Ming-Dauh
AU  - Wang MD
AD  - Eli Lilly and Company, Indianapolis, IN, USA.
FAU - Shen, Tong
AU  - Shen T
AD  - Eli Lilly and Company, Indianapolis, IN, USA.
FAU - Krueger, Kathryn A
AU  - Krueger KA
AD  - Eli Lilly and Company, Indianapolis, IN, USA.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20160112
PL  - England
TA  - Eur Heart J
JT  - European heart journal
JID - 8006263
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Anticholesteremic Agents)
RN  - 0 (Cholesterol, LDL)
RN  - 87PZ955YRB (frovocimab)
RN  - EC 3.4.21.- (PCSK9 protein, human)
RN  - EC 3.4.21.- (Proprotein Convertase 9)
RN  - EC 3.4.21.- (Proprotein Convertases)
RN  - EC 3.4.21.- (Serine Endopeptidases)
RN  - EC 3.4.21.- (Subtilisins)
SB  - IM
CIN - Eur Heart J. 2016 May 1;37(17):1370-2. PMID: 26896250
MH  - Antibodies, Monoclonal/adverse effects/*therapeutic use
MH  - Anticholesteremic Agents
MH  - Cholesterol, LDL
MH  - Double-Blind Method
MH  - Europe
MH  - Humans
MH  - Japan
MH  - Proprotein Convertase 9
MH  - Proprotein Convertases
MH  - Serine Endopeptidases
MH  - Subtilisins
MH  - Treatment Outcome
PMC - PMC4852062
OTO - NOTNLM
OT  - *Hypercholesterolaemia
OT  - *Lipid-lowering therapy
OT  - *Low-density lipoprotein cholesterol
EDAT- 2016/01/14 06:00
MHDA- 2018/04/11 06:00
PMCR- 2016/01/12
CRDT- 2016/01/14 06:00
PHST- 2015/08/12 00:00 [received]
PHST- 2015/12/02 00:00 [accepted]
PHST- 2016/01/14 06:00 [entrez]
PHST- 2016/01/14 06:00 [pubmed]
PHST- 2018/04/11 06:00 [medline]
PHST- 2016/01/12 00:00 [pmc-release]
AID - ehv707 [pii]
AID - 10.1093/eurheartj/ehv707 [doi]
PST - ppublish
SO  - Eur Heart J. 2016 May 1;37(17):1360-9. doi: 10.1093/eurheartj/ehv707. Epub 2016 
      Jan 12.