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Lipoprotein(a)-antisense therapy

Anja Vogt1

  • 1Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ziemssenstraße 1, 80336, Munich, Germany. Anja.Vogt@med.uni-muenchen.de.

Clinical Research in Cardiology Supplements
|March 13, 2019
PubMed

Insights

Elevated lipoprotein(a) (Lp(a)) increases cardiovascular disease risk. New antisense oligonucleotide therapies show significant Lp(a) reduction, offering hope for future cardiovascular event prevention.

Area of Science:

  • Cardiology
  • Genetics
  • Pharmacology

Background:

  • Elevated lipoprotein(a) (Lp(a)) is a significant risk factor for early and severe cardiovascular disease (CVD).
  • Current lipid-modifying therapies, except niacin, do not effectively lower Lp(a), and endpoint trial data is lacking for niacin.
  • Lipoprotein apheresis effectively reduces Lp(a) levels and cardiovascular events, but is invasive.

Purpose of the Study:

  • To evaluate the efficacy and safety of a novel hepatospecific Apo(a) antisense oligonucleotide (IONIS-APO(a)-LRx) for lowering Lp(a).
  • To assess the potential of specific Lp(a) lowering as a therapeutic strategy for cardiovascular risk reduction.

Main Methods:

  • Phase 2 clinical trial of IONIS-APO(a)-LRx in patients with elevated Lp(a).
  • Administration of varying dosages of the antisense oligonucleotide.
  • Monitoring of Lp(a) levels, safety, and tolerability, including injection site reactions.

Main Results:

  • High dosages of IONIS-APO(a)-LRx achieved substantial Lp(a) reductions of 72% and 80%.
  • Achieved Lp(a) levels below 50 mg/dL in 81% and 98% of participants at highest dosages.
  • The drug demonstrated good tolerability and safety, with injection site reactions as the most common side effect.

Conclusions:

  • The hepatospecific Apo(a) antisense oligonucleotide IONIS-APO(a)-LRx demonstrates potent and specific Lp(a) lowering capabilities.
  • These findings support the potential of this novel therapy for reducing cardiovascular risk in individuals with elevated Lp(a).
  • Further Phase 3 trials are anticipated to confirm these results and demonstrate cardiovascular event reduction.

Keywords:
Antisense oligonucleotidesAtherosclerosisCardiovascular diseaseLDL-CholesterolLipid lowering therapy

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