Slide 1: Pooled Safety and Adverse Events in Nine Placebo-controlled Trials of Alirocumab
Peter Jones,1 Harold Bays,2 Umesh Chaudhari,3 Robert Pordy,4 Christelle Lorenzato,5 Kathryn Miller,6 Jennifer Robinson7 1Baylor College of Medicine, Houston, TX, USA; 2Louisville Metabolic and Atherosclerosis Research Center (L-MARC), Louisville, KY, USA; 3Sanofi, Bridgewater, NJ, USA; 4Regeneron.,
Slide 2: Author Disclosure
Author Disclosure Peter Jones Chief Science Officer for National Lipid Association. Participated in a speakers’ bureau for Merck. Consultant/advisory panel for Amgen, Atherotech, Merck, and Sanofi/Regeneron Harold Bays Received research funding from Alere, Amarin, Amgen, Ardea, Astra Zeneca, Boehrin
Slide 3: Background
Inhibition of PCSK9 may provide an effective means to lower LDL-C Alirocumab is a fully human monoclonal antibody to PCSK9 Individual alirocumab trials have shown robust LDL-C reductions and AEs generally comparable with placebo1-12 Pooled safety data are reported from 9 placebo-controlled, randomiz
Slide 4: Nine Placebo-controlled Studies Analyzed
4 Nine Placebo-controlled Studies Analyzed †NCT01288443, 01288469, 01266876, 01812707; ‡NCT01507831, 01623115, 01709500, 01617655, 01644175. Data from LONG TERM, FH I, FH II, HIGH FH taken from pre-specified analysis prior to study completion, which included safety data up to at least 52 weeks for a
Slide 5: Patient Disposition
Patient Disposition (Randomized population) 5 Pool of placebo-controlled studies, % (n) Alirocumab (n=2482) Placebo (n=1277) Randomized and treated 99.8 (2476) >99.9 (1276) Treatment ongoing* (for trials with duration >52 weeks) 55.5 (1377) 55.8 (713) Completed the study treatment period (completed
Slide 6: Patient Baseline Demographics
Pool of placebo-controlled studies Alirocumab (n=2476) Placebo (n=1276) Age, years, mean ± SD 58.6 ± 11.6 58.5 ± 11.3 Males, % (n) 59.9% (1482) 59.8% (763) Race, % (n) White 90.1% (2232) 89.0% (1136) Black or African American 4.1% (101) 4.5% (57) Asian 3.0% (75) 2.9% (37) Ethnicity: Hispanic or Lati
Slide 7: Patient Medical History
Pool of placebo-controlled Phase 3 studies, % (n) Alirocumab (n=2318) Placebo (n=1174) Any CV history/risk factors 80.7 (1870) 81.1 (964) CHD 62.6 (1450) 65.2 (766) Acute MI 32.7 (757) 35.9 (421) Silent MI 3.2 (75) 1.9 (22) Unstable angina 11.8 (274) 14.2 (167) Coronary revascularization procedures
Slide 8: Duration of Study Drug Exposure
Pool of placebo-controlled Phase 3 studies Alirocumab (n=2318) Placebo (n=1174) Cumulative exposure (patient-years) 2727.9 1387.3 Duration of exposure, weeks, mean ± SD 61.6 ± 18. 5 61.7 ± 18.3 Duration of exposure by category, % (n) >52 weeks to <64 weeks 24.8% (576) 23.6% (277) >64 weeks to <76 we
Slide 9: Adverse Events
Pool of placebo-controlled studies, % (n) Alirocumab (n=2476) Placebo (n=1276) Patients with any TEAE 75.8 (1876) 76.4 (975) Patients with any treatment emergent SAE 13.7 (340) 14.3 (182) Patients with any TEAE leading to death 0.5 (13) 0.9 (11) Patients with any TEAE leading to permanent treatment
Slide 10: Adverse Events of Interest
Pool of placebo-controlled studies, % (n) Alirocumab (n=2476) Placebo (n=1276) Hazard ratio (95% CI) Local injection site reaction 7.2 (179) 5.1 (65) 1.48 (1.12 to 1.97) Leading to treatment discontinuation 0.2 (5) 0.4 (5) Potential general allergic event 8.6 (213) 7.8 (99) 1.10 (0.87 to 1.40) Leadi
Slide 11: Positively Adjudicated Cardiovascular Events
Pool of phase 3 placebo-controlled studies, % (n) Alirocumab (n=2318) Placebo (n=1174) Any patients with treatment-emergent positively adjudicated CV event 3.6 (83) 3.5 (41) CHD death 0.3 (6) 0.6 (7) Non-fatal MI 0.7 ( 17) 1.6 (19) Ischemic stroke 0.5 ( 11) 0.2 (2) Unstable angina requiring hospital
Slide 12: Positively Adjudicated MACE Kaplan–Meier Estimates
1174 2318 1160 2294 1098 2171 1057 2087 1026 2030 862 1713 349 698 127 252 84 72 60 48 36 24 12 0 0.06 0.05 0.03 0.02 0.01 0.00 0.04 12 Positively Adjudicated MACE CHD death, Non-fatal MI, Fatal and non-fatal ischemic stroke, Unstable angina requiring hospitalization* Kaplan–Meier Estimates for Time
Slide 13: Clinical Laboratory Data
Alirocumab Placebo Liver function, % (n) (patients with 1 or more abnormal values during TEAE period in pooled placebo-controlled studies) n=2455 n=1266 >3x ULN* 1.7 (41) 1.4 (18) >5x ULN* 0.3 (8) 0.6 (7) >10x ULN* <0.1 (2) 0.2 (3) >20x ULN* <0.1 (1) <0.1 (1) Other clinical laboratory data, Week 52
Slide 14: Conclusions: Alirocumab Pooled Safety
In this large, pooled analysis of 3752 patients 1999 of 2318 in the pooled phase 3 studies (86%) were treated with alirocumab for >52 weeks; total of 2727.9 patient-years of double-blind follow-up Alirocumab AEs were generally comparable with placebo There were more local injection site reactions re