PCSK9 inhibitor reduces LDL-c in patients with HoFH

Introduction and methods

News - Apr. 1, 2020

Alirocumab Efficacy and Safety In Adults With Homozygous Familial Hypercholesterolemia (ODYSSEY HoFH)

Presented at ACC.20 by Dirk J. Blom (Cape Town, South Africa)

Homozygous familial hypercholesterolemia (HoFH) is a genetic disorder characterized by extremely high LDL-c levels. Conventional lipid-lowering therapy (LLT) does not sufficiently lower LDL-c levels or prevent early onset atherosclerotic CVD from occurring in HoFH patients.

The ODDYSEY HoFH (Alirocumab Efficacy and Safety In Adults With Homozygous Familial Hypercholesterolemia) trial evaluated the reduction in LDL-c with the PCSK9 inhibitor alirocumab in adults patients with clinically or genetically diagnosed HoFH. Included were patients (n=69, age ≥18 years, LDL-C ≥70 mg/dL, on stable LLT and/or apheresis) who were randomized to receive a subcutaneous injection of 150 mg alirocumab (n=45) or placebo (n=24) every 2 weeks. Primary endpoint was percentage change from baseline in LDL-c between alirocumab and placebo after 12 weeks. Secondary endpoint measures included percentage change in levels of other lipid parameters (Apo B, non-HDL-C, total cholesterol, Lp(a), HDL-C, TGs, Apo AI) between treatment groups. Safety and tolerability of alirocumab were also assessed. There was an open-label treatment period of 12 weeks and a follow-up period of 8 weeks.

Main results

  • After 12 weeks of treatment, LS mean difference in LDL-c % change from baseline was -35.6 (7.8)% (alirocumab: -26.9 (4.6)% [-62.8 (14.0) mg/dL], placebo: 8.6 (6.3)% [8.9 (19.0) mg/dL]); P <0.0001).
  • Secondary endpoint results (LS mean difference; alirocumab versus placebo) included: ApoB -29.8 (6.3)% (P<0.0001), non-HDL-C -32.9 (7.4)% (P <0.0001), total cholesterol -26.5 (6.2)% (P <0.0001) and Lp(a) -28.4 (6.7)% (P <0.0001).
  • No treatment-emergent SAEs, no discontinuations due to a TEAE and no deaths were reported.


Alirocumab resulted in a statistically significant reduction in LDL-c after 12 weeks of treatment in patients with HoFH. This reduction was seen from first post-baseline assessment at week 4 and was maintained throughout the 12 week treatment period. Other atherogenic lipids and lipoproteins were also significantly reduced with alirocumab, including Apo B, total cholesterol, non-HDL-C and Lp(a). Finally, alirocumab was generally well tolerated with no distinct safety differences versus placebo.


Discussant Eileen Handberg, PhD , (Gainesville, FL, USA) notes that the findings of this trial are consistent with what has been seen with similar drugs. The findings of this study may help with the management of this patient population, which is very difficult to treat and in desperate need for opportunities. She worries though about access to drugs of the PCSK9i class, which is an ongoing issue for this patient group. Having more effective drugs for this difficult-to-treat patient group hopefully leads to a reduction in costs.

– Our coverage of ACC.20 is based on the information provided during the congress –

Watch a video by dr. Blom

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