Efficacy and Safety of Alirocumab in Individuals with Diabetes: Post-hoc analyses from the ODYSSEY LONG TERM Study — ASN Events
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Efficacy and Safety of Alirocumab in Individuals with Diabetes: Post-hoc analyses from the ODYSSEY LONG TERM Study (#213)

Helen M Colhoun 1 , Henry N Ginsberg 2 , Lawrence A Leiter 3 , Umesh Chaudhari 4 , Christelle Lorenzato 5 , Robert Pordy 6 , Jennifer G Robinson 7 , Gerald Watts 8 , Richard O'Brien 9
  1. University of Dundee, Dundee, Scotland
  2. Columbia University, New York, NY, USA
  3. Li Ka Shing Knowledge Institute and Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Ontario, Canada
  4. Sanofi, Bridgewater, NJ, USA
  5. Sanofi, Chilly-Mazarin, France
  6. Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA
  7. University of Iowa, Iowa City, IA, USA
  8. University of Western Australia, Crawley, WA, Australia
  9. University of Melbourne, Parkville, VIC, Australia

Dyslipidaemia is a major risk factor for cardiovascular disease (CVD) in diabetes (DM). Despite increasing use of statins in this population, a significant proportion remain at increased residual risk of CVD. This may relate to inadequate correction of the accumulation of atherogenic apoB containing particles in plasma, specifically LDL and remnants lipoproteins. PCSK9 monoclonal antibodies (mAbs) inhibit proprotein convertase subtilisin–kexin type 9 (PCSK9), a secretory protease and cell surface receptor regulator, and, in diabetes can potentially further increase the catabolism of atherogenic apoB containing lipoproteins, lowering their concentration in plasma and accordingly the risk of CAD. Experience with the use of PCSK9 mAbs in diabetes is limited.

We conducted a post-hoc analysis of data from the ODYSSEY LONG TERM study (NCT01507831) to compare the effects of alirocumab (ALI) in individuals with and without DM. Patients (2,341; 832 [35.5%] with DM) at high CVD risk and LDL-C ≥ 1.81 mmol/L on maximally tolerated statin ± other lipid-lowering therapy, were randomized (2:1) to ALI 150 mg or placebo Q2W (as 1 mL injection) for 78 weeks. Planned analyses: efficacy at 24 weeks, safety up to 78 weeks.

At week 24, the difference between ALI and placebo in the mean percentage change from baseline in calculated LDL-C level was -59.0% in those with DM and -63.4% in those without (p=0.0957 for interaction). Decreases in TGs (-18.5% vs -16.7%, p=0.5430) and increases in HDL-C (3.2% vs 5.4%, p=0.1078) were also similar between subgroups. At week 78, there was no difference in adverse events in those with versus those without DM. In post-hoc analyses, CV event rates were lower with ALI vs placebo in those with DM (hazard ratio 0.41; 95% CI 0.18-0.96).

LDL-C reduction with ALI vs placebo was independent of DM status at baseline, with no specific safety signals observed up to 78 weeks. The large ongoing ODYSSEY OUTCOMES study is evaluating ALI treatment for potential reduction of CV events.

Disclosures: Analysis funded by Sanofi and Regeneron Pharmaceuticals, Inc. Editorial assistance (Scriptix Pty Ltd) funded by Sanofi Australia Pty Ltd. Data first presented at: ADA 75th Scientific Sessions, June 5-9 2015, Boston, MA, USA.