G Kees Hovingh1, Frederick J Raal2, Ricardo Dent3, Claudia Stefanutti4, Olivier Descamps5, Luis Masana6, Armando Lira7, Ian Bridges8, Blai Coll7, David Sullivan9. 1. Department of Vascular Medicine, Academisch Medisch Centrum, Amsterdam, The Netherlands. Electronic address: g.k.hovingh@amc.uva.nl. 2. Faculty of Health Sciences, Department of Medicine, University of the Witwatersrand, Johannesburg, South Africa. 3. Clinical Development Department, Amgen (Europe) GmbH, Zug, Switzerland. 4. Department of Molecular Medicine, Umberto I Hospital, Sapienza University of Rome, Rome, Italy. 5. Centres Hospitaliers Jolimont, Lipid Clinic, Haine-Saint-Paul, Belgium. 6. Internal Medicine Department, Hospital Universitari Sant Joan, Lipids and Arteriosclerosis Research Unit, Universitat Rovira i Virgili, IISPV, CIBERDEM, Reus, Spain. 7. Clinical Development Department, Amgen Inc, One Amgen Center Drive, Thousand Oaks, CA, USA. 8. Biostatistics Department, Amgen Ltd, Cambridge, United Kingdom. 9. Department of Clinical Biochemistry, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
Abstract
BACKGROUND:Evolocumab, a fully human monoclonal antibody against proprotein convertase subtilisin/kexin type 9, is safe and effective when dosed biweekly (Q2W) or monthly (QM) in patients with heterozygous familial hypercholesterolemia (HeFH) as demonstrated in two 12-week trials: Reduction of LDL-C With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder (RUTHERFORD; phase 2) and RUTHERFORD-2 (phase 3). OBJECTIVE: The objective of the study was to evaluate long-term efficacy, safety, and tolerability of evolocumab during open-label extension trials. METHODS: Patients completing parent trials were re-randomized 2:1 to evolocumab plus standard of care (SOC) or SOC alone for 52 weeks (Open-Label Study of Long-term Evaluation Against LDL-C [OSLER-1]) or 48 weeks (OSLER-2). Evolocumab dosing was 420 mg QM (OSLER-1) and 140 mg Q2W or 420 mg QM (OSLER-2). A pooled analysis of OSLER data was performed from this subset of HeFH patients. RESULTS:Four hundred forty HeFH patients from RUTHERFORD (n = 147) and RUTHERFORD-2 (n = 293) (mean [standard deviation] age 51 [12] years, 58% male, 90% White) were randomized to evolocumab plus SOC (n = 289) or SOC (n = 151). The 48-week period was completed by 425 patients (96.6%). Eight patients discontinued evolocumab plus SOC (2.8%) and 7 discontinued SOC (4.6%). Compared to parent study baseline, patients receiving evolocumab plus SOC experienced a mean 53.6% reduction in low-density lipoprotein cholesterol after 48 weeks. No patient experienced an adverse event leading to permanent evolocumab discontinuation during the 1-year SOC-controlled period. Serious adverse event rates were similar between groups (evolocumab plus SOC, 7.3%; SOC, 8.6%). CONCLUSION: Continued use of evolocumab added to SOC in patients with HeFH yields persistent and marked low-density lipoprotein cholesterol reductions during 48 weeks of follow-up. Long-term dosing of evolocumab with SOC was safe and well tolerated.
RCT Entities:
BACKGROUND:Evolocumab, a fully human monoclonal antibody against proprotein convertase subtilisin/kexin type 9, is safe and effective when dosed biweekly (Q2W) or monthly (QM) in patients with heterozygous familial hypercholesterolemia (HeFH) as demonstrated in two 12-week trials: Reduction of LDL-C With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder (RUTHERFORD; phase 2) and RUTHERFORD-2 (phase 3). OBJECTIVE: The objective of the study was to evaluate long-term efficacy, safety, and tolerability of evolocumab during open-label extension trials. METHODS:Patients completing parent trials were re-randomized 2:1 to evolocumab plus standard of care (SOC) or SOC alone for 52 weeks (Open-Label Study of Long-term Evaluation Against LDL-C [OSLER-1]) or 48 weeks (OSLER-2). Evolocumab dosing was 420 mg QM (OSLER-1) and 140 mg Q2W or 420 mg QM (OSLER-2). A pooled analysis of OSLER data was performed from this subset of HeFH patients. RESULTS: Four hundred forty HeFH patients from RUTHERFORD (n = 147) and RUTHERFORD-2 (n = 293) (mean [standard deviation] age 51 [12] years, 58% male, 90% White) were randomized to evolocumab plus SOC (n = 289) or SOC (n = 151). The 48-week period was completed by 425 patients (96.6%). Eight patients discontinued evolocumab plus SOC (2.8%) and 7 discontinued SOC (4.6%). Compared to parent study baseline, patients receiving evolocumab plus SOC experienced a mean 53.6% reduction in low-density lipoprotein cholesterol after 48 weeks. No patient experienced an adverse event leading to permanent evolocumab discontinuation during the 1-year SOC-controlled period. Serious adverse event rates were similar between groups (evolocumab plus SOC, 7.3%; SOC, 8.6%). CONCLUSION: Continued use of evolocumab added to SOC in patients with HeFH yields persistent and marked low-density lipoprotein cholesterol reductions during 48 weeks of follow-up. Long-term dosing of evolocumab with SOC was safe and well tolerated.
Authors: Henry N Ginsberg; Jaakko Tuomilehto; G Kees Hovingh; Bertrand Cariou; Raul D Santos; Alan S Brown; Santosh K Sanganalmath; Andrew Koren; Desmond Thompson; Frederick J Raal Journal: Cardiovasc Drugs Ther Date: 2019-02 Impact factor: 3.727
Authors: Krzysztof Chlebus; Barbara Cybulska; Piotr Dobrowolski; Marzena Romanowska-Kocejko; Marta Żarczyńska-Buchowiecka; Natasza Gilis-Malinowska; Aneta Stróżyk; Justyna Borowiec-Wolna; Marcin Pajkowski; Beata Bobrowska; Renata Rajtar-Salwa; Aleksandra Kwapiszewska; Małgorzata Waluś-Miarka; Magdalena Chmara; Rafał Gałąska; Maciej Małecki; Tomasz Zdrojewski; Marcin Gruchała Journal: Cardiol J Date: 2022-02-11 Impact factor: 2.737