Durability of Alirocumab effect: data from an open-label extension to the ODYSSEY program for patients with heterozygous familial hypercholesterolemia
M. Farnier*a (Dr), GK. Hovinghb (Dr), G. Langsetc (Dr), R. Dufourd (Dr), M. Baccara-Dinete (Dr), C. Din-Bellf (Mme), G. Manveliang (Dr), JR. Guytonh (Dr)
a Lipid clinic - Point Médical, Dijon, FRANCE ; b Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands, Amsterdam, PAYS-BAS ; c Lipid Clinic, Oslo University Hospital, Oslo, NORVÈGE ; d Institut de recherches cliniques de Montréal and Université de Montréal, Montréal, Qc, CANADA ; e Clinical Development, R&D, Sanofi, Montpellier, FRANCE ; f Biostatistics and Programming, Sanofi, Chilly-Mazarin, FRANCE ; g Regeneron Pharmaceuticals, Tarrytown, Ny, ÉTATS-UNIS ; h Duke University Medical Center, Durham, Nc, ÉTATS-UNIS
* mcihelfarnier@nerim.net
Purpose: To evaluate the overall durability of the effect of alirocumab in patients with heterozygous familial hypercholesterolemia (HeFH) using data from the ODYSSEY open-label extension (OLE) of four Phase 3 trials (FHI, FHII, LONG-TERM, HIGH-FH) assessing long-term efficacy and safety for up to 40 months.
Methods: Patients received alirocumab 75 mg (FHI, FHII, LONG-TERM) or 150 mg (HIGH-FH) once every 2 weeks. From Week 12, dose adjustment of alirocumab was allowed as per investigator’s clinical judgement.
Results: A total of 985 patients (mean age 54.4 years, 55.8% male) were included in OLE safety population. At OLE enrollment, 978 patients were receiving statins with 627 other lipid-lowering therapy. At the time of analysis, 938 patients had completed ≥1 year of treatment; 5.7% had discontinued treatment (2.2% due to adverse events). Of those who started OLE on 75 mg dose, 537/909 (59.1%) were maintained on that dose throughout. At Week 48 of OLE, the mean LDL-C was 79.7 mg/dL, a mean reduction of 46.9% compared with baseline levels of the parent studies. Other lipid changes included reductions at Week 48 in non-high density lipoprotein cholesterol (40.3%), total cholesterol (29.7%), lipoprotein(a) (25.6%), and apolipoprotein B (37.5%). Overall, 762/985 (77.4%) patients reported treatment-emergent adverse events during OLE (up to 73 weeks). Injection site reactions reported by 49 patients (5.0%) were mild and self limited.
Conclusion: In this OLE study of patients with HeFH, alirocumab demonstrated a durable and robust treatment effect, yielding a 47% reduction in LDL-C at Week 48 compared with baseline levels.
L’auteur a déclaré le(s) conflit(s) d’intérêt suivant(s) :
Le docteur Michel Farnier déclare avoir reçu des honoraires en tant qu’investigateur, expert scientifique et/ou conférencier de la part des firmes suivantes :
Abbott/Mylan, Akcea/Ionis, Amgen, AstraZeneca, Eli Lilly, Kowa, Merck and Co, Pfizer, Roche, Sanofi/Regeneron et Servier