TY - JOUR
T1 - Alirocumab in patients with heterozygous familial hypercholesterolaemia undergoing lipoprotein apheresis
T2 - The ODYSSEY ESCAPE trial
AU - Moriarty, Patrick M.
AU - Parhofer, Klaus G.
AU - Babirak, Stephan P.
AU - Cornier, Marc Andre
AU - Duell, P. Barton
AU - Hohenstein, Bernd
AU - Leebmann, Josef
AU - Ramlow, Wolfgang
AU - Schettler, Volker
AU - Simha, Vinaya
AU - Steinhagen-Thiessen, Elisabeth
AU - Thompson, Paul D.
AU - Vogt, Anja
AU - Von Stritzky, Berndt
AU - Du, Yunling
AU - Manvelian, Garen
N1 - Funding Information:
We thank the patients, study coordinators and investigators, and the following persons from the sponsors for their contributions to critical review of the manuscript: Regeneron: William J. Sasiela, PhD, Robert, Pordy, MD, Johanna Mendoza, BSc, and Carol Hudson, BPharm; Sanofi: Jay Edelberg, MD, PhD, L. Veronica Lee, MD, Tu Nguyen, MD, and Michael Howard, MBA. The authors thank Dr Claudia Stefanutti for her assistance in designing the ODYSSEY ESCAPE protocol. Writing support was provided by Sophie K. Rushton-Smith, PhD, funded by Sanofi and Regeneron Pharmaceuticals, Inc.
Funding Information:
personal fees from Genzyme, personal fees from Duke, personal fees from Esperion, personal fees from Eliaz Therapeutics, personal fees from Alexion, grants from Pfizer, grants from Catabasis, grants from Novartis, grants from Kaneka, personal fees from Aegerion, personal fees from Amarin, personal fees from Lilly, outside the submitted work. Dr Parhofer reports grants and personal fees from Sanofi/Regeneron, during the conduct of the study; personal fees from Sanofi-Aventis, grants and personal fees from Regeneron, personal fees from Aegerion, grants and personal fees from Merck, Sharp & Dohme, personal fees from Amgen, personal fees from Boehringer Ingelheim, personal fees from Pfizer, outside the submitted work. Dr Babirak reports other from Sanofi, other from Amgen, during the conduct of the study; other from Sanofi, other from Amgen, outside the submitted work. Dr Cornier reports grants from Regeneron, outside the submitted work. Dr Duell reports grants from Regeneron, during the conduct of the study; personal fees from Regeneron, personal fees from Amgen, personal fees from Kaneka, outside the submitted work. Dr Hohenstein reports personal fees from Amgen GmBH, grants and personal fees from Kaneka Pharma Europe N.V., personal fees from Miltenyi Biotec GmbH, personal fees from Fresenius Medical Care GmbH, grants and personal fees from B. Braun Avitum, personal fees from Sanofi-Aventis, grants and personal fees from Novartis, personal fees from Alexion Pharma, outside the submitted work. Dr Leebmann reports nothing to disclose. Dr Ramlow reports grants and personal fees from Amgen, grants and personal fees from Fresenius, grants and personal fees from Kaneka, personal fees from Aegerion, personal fees from B. Braun, personal fees from Merck Sharp & Dohme, personal fees from Regeneron Pharmaceuticals Inc., personal fees from Sanofi, outside the submitted work. Dr Schettler reports support for lectures from Sanofi-Aventis. Dr Simha reports nothing to disclose. Dr Steinhagen-Thiessen reports nothing to disclose. Dr Thompson reports other from Regeneron, other from Sanofi, other from Amgen, outside the submitted work. Dr Vogt reports other from Sanofi/Regeneron Pharmaceuticals, during the conduct of the study; other from Sanofi/Regeneron Pharmaceuticals, other from Sanofi/Regeneron Pharmaceuticals, outside the submitted work. Dr von Stritzky is an employee of Sanofi Germany. Dr Du is an employee of Regeneron Pharmaceuticals Inc. Dr Manvelian is an employee of Regeneron Pharmaceuticals Inc.
Publisher Copyright:
© The Author 2016.
PY - 2016/12/21
Y1 - 2016/12/21
N2 - Aim: To evaluate the effect of alirocumab on frequency of standard apheresis treatments [weekly or every 2 weeks (Q2W)] in heterozygous familial hypercholesterolaemia (HeFH). Methods and results: ODYSSEY ESCAPE (NCT02326220) was a double-blind study in 62 HeFH patients undergoing regular weekly or Q2W lipoprotein apheresis. Patients were randomly assigned (2:1, respectively) to receive alirocumab 150mg (n=41) or placebo (n=21) Q2W subcutaneously for 18 weeks. From day 1 to week 6, apheresis rate was fixed according to the patient's established schedule; from weeks 7 to 18, apheresis rate was adjusted based on the patient's low-density lipoprotein cholesterol (LDL-C) response in a blinded fashion. Apheresis was not performed when the LDL-C value was-30% lower than the baseline (pre-apheresis) value. The primary efficacy endpoint was the rate of apheresis treatments over 12 weeks (weeks 7-18), standardized to number of planned treatments. In the alirocumab group the least square (LS) mean6SE (95% confidence interval [CI]) per cent change in pre-apheresis LDL-C from baseline at week 6 was-53.762.3 (-58.2 to-49.2) compared with 1.663.1 (-4.7 to 7.9) in the placebo group. The primary efficacy endpoint showed statistically significant benefit in favour of alirocumab (Hodges-Lehmann median estimate of treatment difference: 0.75; 95% CI 0.67-0.83; P<0.0001). Therefore, alirocumabtreated patients had a 0.75 (75%) additional reduction in the standardized rate of apheresis treatments vs. placebo-treated patients. During this period, 63.4% of patients on alirocumab avoided all and 92.7% avoided at least half of the apheresis treatments. Adverse event rates were similar (75.6% of patients on alirocumab vs. 76.2% on placebo). Conclusions: Lipoprotein apheresis was discontinued in 63.4% of patients on alirocumab who were previously undergoing regular apheresis, and the rate was at least halved in 92.7% of patients. Alirocumab was generally safe and well tolerated.
AB - Aim: To evaluate the effect of alirocumab on frequency of standard apheresis treatments [weekly or every 2 weeks (Q2W)] in heterozygous familial hypercholesterolaemia (HeFH). Methods and results: ODYSSEY ESCAPE (NCT02326220) was a double-blind study in 62 HeFH patients undergoing regular weekly or Q2W lipoprotein apheresis. Patients were randomly assigned (2:1, respectively) to receive alirocumab 150mg (n=41) or placebo (n=21) Q2W subcutaneously for 18 weeks. From day 1 to week 6, apheresis rate was fixed according to the patient's established schedule; from weeks 7 to 18, apheresis rate was adjusted based on the patient's low-density lipoprotein cholesterol (LDL-C) response in a blinded fashion. Apheresis was not performed when the LDL-C value was-30% lower than the baseline (pre-apheresis) value. The primary efficacy endpoint was the rate of apheresis treatments over 12 weeks (weeks 7-18), standardized to number of planned treatments. In the alirocumab group the least square (LS) mean6SE (95% confidence interval [CI]) per cent change in pre-apheresis LDL-C from baseline at week 6 was-53.762.3 (-58.2 to-49.2) compared with 1.663.1 (-4.7 to 7.9) in the placebo group. The primary efficacy endpoint showed statistically significant benefit in favour of alirocumab (Hodges-Lehmann median estimate of treatment difference: 0.75; 95% CI 0.67-0.83; P<0.0001). Therefore, alirocumabtreated patients had a 0.75 (75%) additional reduction in the standardized rate of apheresis treatments vs. placebo-treated patients. During this period, 63.4% of patients on alirocumab avoided all and 92.7% avoided at least half of the apheresis treatments. Adverse event rates were similar (75.6% of patients on alirocumab vs. 76.2% on placebo). Conclusions: Lipoprotein apheresis was discontinued in 63.4% of patients on alirocumab who were previously undergoing regular apheresis, and the rate was at least halved in 92.7% of patients. Alirocumab was generally safe and well tolerated.
KW - Alirocumab
KW - Familial hypercholesterolaemia
KW - Low-density lipoprotein cholesterol
KW - Low-density lipoprotein receptor
KW - Monoclonal antibody
KW - Proprotein convertase subtilisin/kexin type 9
UR - http://www.scopus.com/inward/record.url?scp=85014503636&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85014503636&partnerID=8YFLogxK
U2 - 10.1093/eurheartj/ehw388
DO - 10.1093/eurheartj/ehw388
M3 - Article
C2 - 27572070
AN - SCOPUS:85014503636
SN - 0195-668X
VL - 37
SP - 3588
EP - 3595
JO - European heart journal
JF - European heart journal
IS - 48
ER -