Homozygous familial hypercholesterolemia: evinacumab plus max statins yields LDL decline

  • Raal FJ & al.
  • N Engl J Med
  • 20 Aug 2020

  • curated by Emily Willingham, PhD
  • Clinical Essentials
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Takeaway

  • Evinacumab added to maximum statins for patients with homozygous familial hypercholesterolemia (HoFH) yielded a 49 percentage point difference in low-density lipoprotein cholesterol (LDL-C) vs a slight increase in the placebo group.
  • 24-week results from the randomized ELIPSE HoFH trial.

Why this matters

  • Evinacumab treatment in a small open-label phase 2 study yielded a similar 49% reduction from baseline LDL-C levels.

Key results

  • 43 in evinacumab group vs 22 receiving placebo.
    • 94% were receiving statins (77% receiving high-intensity statins).
    • Other therapies included PCSK9 inhibitor, ezetimibe, lomitapide.
    • 63% were receiving at least 3 lipid-modifying drugs.
  • At week 24, LDL-C:
    • Had declined in the evinacumab group by 47.1% from baseline.
    • Had increased in the placebo group by 1.9%.
    • Between-group least squares mean difference was −49.0 (95% CI, −65.0 to −33.1) percentage points.
    • This difference in terms of LDL-C level was −132 (95% CI, −175 to −89) mg/dL.
  • Results were similar regardless of background therapy.
  • The evinacumab group also had desirable declines in other lipids.
  • Adverse events: 66% with evinacumab, 81% with placebo.
  • Liver enzyme increase: 5% with evinacumab, 10% with placebo.
  • Only a few patients had preexisting antibodies to evinacumab, which did not seem to affect pharmacokinetics.
  • No cardiovascular events.

Study design

  • Double-blind, placebo-controlled phase 3 trial.
  • Evinacumab dose: 15 mg/kg body weight infusion every 4 weeks.
  • Funding: Regeneron Pharmaceuticals.

Limitations

  • Relatively short, small number of patients.