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

John J P Kastelein, Henry N Ginsberg, Gisle Langslet, G Kees Hovingh, Richard Ceska, Robert Dufour, Dirk Blom, Fernando Civeira, Michel Krempf, Christelle Lorenzato, Jian Zhao, Robert Pordy, Marie T Baccara-Dinet, Daniel A Gipe, Mary Jane Geiger, Michel Farnier, John J P Kastelein, Henry N Ginsberg, Gisle Langslet, G Kees Hovingh, Richard Ceska, Robert Dufour, Dirk Blom, Fernando Civeira, Michel Krempf, Christelle Lorenzato, Jian Zhao, Robert Pordy, Marie T Baccara-Dinet, Daniel A Gipe, Mary Jane Geiger, Michel Farnier

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.

© The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

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.

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