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Clinical Trial
. 2015 Nov 14;36(43):2996-3003.
doi: 10.1093/eurheartj/ehv370. Epub 2015 Sep 1.

ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia

John J P Kastelein  1 , Henry N Ginsberg  2 , Gisle Langslet  3 , G Kees Hovingh  4 , Richard Ceska  5 , Robert Dufour  6 , Dirk Blom  7 , Fernando Civeira  8 , Michel Krempf  9 , Christelle Lorenzato  10 , Jian Zhao  11 , Robert Pordy  12 , Marie T Baccara-Dinet  13 , Daniel A Gipe  12 , Mary Jane Geiger  12 , Michel Farnier  14
Affiliations
Clinical Trial

ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia

John J P Kastelein et al. Eur Heart J. .

Abstract

Aims: 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).

Methods and 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).

Conclusion: 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.

Clinical trial registration: Cinicaltrials.gov (identifiers: NCT01623115; NCT01709500).

Keywords: Alirocumab; Cardiovascular risk; Heterozygous familial hypercholesterolaemia; LDL-C; PCSK9.

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Figures

Figure 1
Figure 1
Randomization and treatment. ITT, intention-to-treat. Completion of the study was defined as follows: last study-drug injection received (Week 76) and end-of-treatment visit (Week 78) occurred within 21 days of last injection and at least 525 days post-randomization.
Figure 2
Figure 2
Levels of calculated LDL-C over time (intention-to-treat analysis). ALI, alirocumab; PBO, placebo.
See this image and copyright information in PMC

Comment in

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