ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia.
OBJECTIVE
To assess long-term (78 weeks) alirocumab treatment in patients with heterozygous familial hypercholesterolaemia (HeFH) and inadequate LDL-C control on maximally tolerated lipid-lowering therapy (LLT).


RESULTS
In two randomized, double-blind studies (ODYSSEY FH I, n = 486; FH II, n = 249), patients were randomized 2 : 1 to alirocumab 75 mg or placebo every 2 weeks (Q2W). Alirocumab dose was increased at Week 12 to 150 mg Q2W if Week 8 LDL-C was ≥1.8 mmol/L (70 mg/dL). Primary endpoint (both studies) was percentage change in calculated LDL-C from baseline to Week 24. Mean LDL-C levels decreased from 3.7 mmol/L (144.7 mg/dL) at baseline to 1.8 mmol/L (71.3 mg/dL; -57.9% vs. placebo) at Week 24 in patients randomized to alirocumab in FH I and from 3.5 mmol/L (134.6 mg/dL) to 1.8 mmol/L (67.7 mg/dL; -51.4% vs. placebo) in FH II (P < 0.0001). These reductions were maintained through Week 78. LDL-C <1.8 mmol/L (regardless of cardiovascular risk) was achieved at Week 24 by 59.8 and 68.2% of alirocumab-treated patients in FH I and FH II, respectively. Adverse events resulted in discontinuation in 3.4% of alirocumab-treated patients in FH I (vs. 6.1% placebo) and 3.6% (vs. 1.2%) in FH II. Rate of injection site reactions in alirocumab-treated patients was 12.4% in FH I and 11.4% in FH II (vs. 11.0 and 7.4% with placebo).


CONCLUSIONS
In patients with HeFH and inadequate LDL-C control at baseline despite maximally tolerated statin ± other LLT, alirocumab treatment resulted in significant LDL-C lowering and greater achievement of LDL-C target levels and was well tolerated.


BACKGROUND
Cinicaltrials.gov (identifiers: NCT01623115; NCT01709500).
Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Room F4-159.2, 1105 AZ Amsterdam, The Netherlands j.j.kastelein@amc.uva.nl.
John J P
JJ
Kastelein
Columbia University, New York, NY, USA.
Henry N
HN
Ginsberg
Lipid Clinic, Oslo University Hospital, Oslo, Norway.
Gisle
G
Langslet
Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Room F4-159.2, 1105 AZ Amsterdam, The Netherlands.
G Kees
GK
Hovingh
Center of Preventive Cardiology, 1st School of Medicine and University Hospital, Charles University, Prague, Czech Republic.
Richard
R
Ceska
Institut de Recherches Cliniques de Montréal, Montréal, Canada.
Robert
R
Dufour
Division of Lipidology, Department of Medicine, University of Cape Town and MRC Cape Heart Group, Cape Town, South Africa.
Dirk
D
Blom
Lipid Unit, Hospital Universitario Miguel Servet, Zaragoza, Spain.
Fernando
F
Civeira
CHU de Nantes-Hôpital Nord Laennec, Saint-Herblain, France.
Michel
M
Krempf
Sanofi, Paris, France.
Christelle
C
Lorenzato
Regeneron Pharmaceuticals, Inc., Basking Ridge, NJ, USA.
Jian
J
Zhao
Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
Robert
R
Pordy
Sanofi, Montpellier, France.
Marie T
MT
Baccara-Dinet
Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
Daniel A
DA
Gipe
Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
Mary Jane
MJ
Geiger
Point Médical, Dijon, France.
Michel
M
Farnier
D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008078:Cholesterol, LDL / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; C571059:alirocumab
Alirocumab; Cardiovascular risk; Heterozygous familial hypercholesterolaemia; LDL-C; PCSK9