Oral Muvalaplin for Lowering of Lipoprotein(a) - KRAKEN

Nov 18, 2024
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Author/Summarized by Author:
Anthony A. Bavry, MD,MPH,FACC
Summary Reviewer:
Kim A. Eagle, MD, MACC
Trial Sponsor:
Eli Lilly and Company
Date Presented:
11/18/2024
Date Published:
11/18/2024
Original Posted Date:
11/18/2024
References

Contribution To Literature:

The KRAKEN trial showed that among patients with high cardiovascular risk and elevated lipoprotein(a), muvalaplin reduces lipoprotein(a) levels.

Description:

The goal of this phase 2 trial was to evaluate muvalaplin compared with placebo among patients with high cardiovascular risk and elevated lipoprotein(a). Muvalaplin targets assembly of the lipoprotein(a) particle.

Study Design

  • Randomized
  • Parallel
  • Blinded
  • Placebo

Patients with high cardiovascular risk and elevated lipoprotein(a) were randomized to oral muvalaplin 10 mg daily (n = 34) vs. muvalaplin 60 mg daily (n = 64), vs. muvalaplin 240 mg daily (n = 68), vs. placebo (n = 67).

  • Total number of enrollees: 233
  • Duration of follow-up: 12 weeks
  • Mean patient age: 67 years
  • Percentage female: 32%
  • Percentage with diabetes: 32%

Inclusion criteria:

  • Patients ≥40 years of age with high cardiovascular risk (coronary artery disease, ischemic stroke, peripheral arterial disease, type 2 diabetes, or familial hypercholesterolemia)
  • Elevated lipoprotein(a) (≥175 nmol/L)

Exclusion criteria:

  • Uncontrolled diabetes or hypertension
  • Estimated glomerular filtration rate <30 mL/min/1.73 m2
  • Body mass index <18.5 or >40 kg/m2
  • Any cardiovascular event or surgery in the last 3 months
  • Any unstable medical state

Principal Findings:

The primary outcome, percent change in lipoprotein(a) concentration from baseline to 12 weeks, was: -47.7 in the 10 mg daily group vs. -81.6 in the 60 mg daily group vs. -85.7 in the 240 mg daily group.

Secondary outcomes:

Serious adverse events were reported in <6% of participants in each group.

Interpretation:

Among patients with high cardiovascular risk and elevated lipoprotein(a), oral muvalaplin reduces lipoprotein(a) at 12 weeks. Serious adverse events related to the study drug were infrequent. These findings support further evaluation of muvalaplin in phase 3 clinical trials.

References:

Nicholls SJ, Ni W, Rhodes GM, et al. Oral Muvalaplin for Lowering of Lipoprotein(a): A Randomized Clinical Trial. JAMA 2024;Nov 18:[Epub ahead of print.

Presented by Dr. Stephen Nicholls at the American Heart Association Scientific Sessions, Chicago, IL, November 18, 2024.

Clinical Topics: Dyslipidemia, Advanced Lipid Testing, Lipid Metabolism, Prevention

Keywords: AHA24, AHA Annual Scientific Sessions, Atherosclerosis, Dyslipidemia, Lipoprotein(a)


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