Abstract 17070: Efficacy and Safety of Alirocumab: Pooled Analyses of 1048 Individuals With Diabetes Mellitus From Five Placebo-controlled Phase 3 Studies of at Least 52 Weeks Duration
Background: Individuals with diabetes (DM) are at high risk for CVD and may not achieve adequate control of LDL-C levels with current lipid-lowering therapies.
Aim: To assess alirocumab (ALI) efficacy and safety in individuals with and without baseline DM.
Methods: Five placebo (PBO)-controlled Phase 3 studies of 52-78 weeks were analyzed, comprising 1048 individuals with DM at study entry and 2444 with no DM (safety population). All individuals had hypercholesterolemia, and were on maximally tolerated background statin therapy. Efficacy data were pooled by initial ALI dose; 3 studies (n=1043, ITT analysis) used PBO or ALI 75 mg every 2 weeks (Q2W), increasing to 150 mg Q2W at W12 if LDL-C at W8 ≥ 70 mg/dL; 2 studies (n=2416, ITT analysis) initiated treatment with PBO or ALI 150 mg Q2W. All doses were 1 mL SC injection. Safety data were pooled for all 5 studies. Efficacy data are reported to W24, safety for ≥52 weeks.
Results: Individuals with DM had lower mean baseline LDL-C levels. At W12, ALI 75 mg Q2W significantly reduced LDL-C levels from baseline vs PBO with treatment effect consistent regardless of DM status (Table). A higher proportion of participants with no DM received a dose increase at W12, leading to a greater magnitude of reduction at W24 in that group.
For those initiating at ALI 150 mg Q2W, LDL-C reductions of 58.3% (DM) and 62.3% (no DM) vs PBO were achieved at W24 (Table).
Improvements were seen in other parameters, including TGs, HDL-C, and Lp(a), largely irrespective of baseline DM status.
Adverse event (AE) rates were generally comparable in both groups. AEs occurring in ≥5% of individuals in all subgroups were nasopharyngitis and URI. Injection site reactions (ISRs) were less frequent in those with DM: ALI 3.6% and PBO 2.8%, vs no DM: ALI 8.4% and PBO 6.1%.
Conclusions: ALI demonstrated robust LDL-C reductions in individuals with and without DM. Safety observations were generally similar regardless of DM status, although those with DM reported fewer ISRs than those without.
Author Disclosures: H.N. Ginsberg: Other Research Support; Modest; Amgen. Honoraria; Modest; Sanofi Regeneron, Amgen, Merck, Kowa. Consultant/Advisory Board; Modest; Sanofi Regeneron, Amgen, Merck, Reverlogix. Research Grant; Significant; Sanofi Regeneron. Other Research Support; Significant; Merck. M. Farnier: Other Research Support; Significant; Sanofi, Regeneron, Amgen. Speakers Bureau; Significant; Abbott, Roche, Sanofi, Regeneron. Consultant/Advisory Board; Modest; Pfizer, Eli Lilly, AstraZeneca, Kowa. Consultant/Advisory Board; Significant; Sanofi, Regeneron, Amgen, Merck & Co. J.G. Robinson: Research Grant; Significant; Amarin, Amgen, AstraZeneca, Eisai, GlaxoSmithKline, Merck, Pfizer, Regeneron, Sanofi, Takeda. Consultant/Advisory Board; Modest; Merck, Eli Lilly. Consultant/Advisory Board; Significant; Amgen, Pfizer, Regeneron, Sanofi. C.P. Cannon: Research Grant; Modest; Accumetrics. Research Grant; Significant; Arisaph, AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Janssen, Merck, Takeda. Consultant/Advisory Board; Modest; CSL Behring, Essentialis, GlaxoSmithKline, Merck, Kowa, Takeda, BMS, Pfizer. Consultant/Advisory Board; Significant; Sanofi, Regeneron Pharmaceuticals, Lipimedix. N. Sattar: Honoraria; Modest; Merck. Consultant/Advisory Board; Modest; Sanofi, Amgen, Eli Lilly, Boehringer Ingelheim, AstraZeneca, Merck. Other; Modest; Involved in the conduct of the GAUSS-3 clinical trial of PCSK9 inhibition in patients with reported statin intolerance, sponsored by Amgen. M.T. Baccara-Dinet: Employment; Significant; Sanofi. C. Lorenzato: Employment; Significant; Sanofi. M. Bujas-Bobanovic: Employment; Significant; Sanofi. M.J. Louie: Employment; Significant; Regeneron Pharmaceuticals, Inc. H.M. Colhoun: Research Grant; Modest; Pfizer, Roche, AstraZeneca, Boehringer-Ingelheim, Sanofi, Eli Lilly. Speakers Bureau; Significant; Sanofi, Regeneron. Honoraria; Significant; Sanofi, Regeneron. Ownership Interest; Modest; Roche. Consultant/Advisory Board; Significant; Regeneron, Sanofi. Other; Modest; Novartis, Merck.
- © 2015 by American Heart Association, Inc.