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Muvalaplin treatment was associated with swift and large reductions in lipoprotein a (Lp(a)) levels in patients with elevated Lp(a) levels and a heightened risk for adverse cardiovascular events in the KRAKEN study. Whether this orally administered agent may reduce cardiovascular events in this population requires further investigation.

Prof. Stephen Nicholls, MBBS, PhD, from the University of Melbourne, in Australia, and co-investigators evaluated the safety and efficacy of muvalaplin, an orally administered agent that disrupts the bonding of Apo(a) and ApoB, resulting in a decreased formation of Lp(a)^1,2. The current phase 2 KRAKEN study (NCT05563246) included patients over 40 years of age with elevated Lp(a) levels (i.e. ≥175 nmol/L) and a high risk for cardiovascular events. The participants were randomly assigned to placebo (n=67), muvalaplin 10 mg (n=34), 60 mg (n=64), or 240 mg (n=68), administered at weeks 0, 1, 2, 4, 8, and 12. The primary analysis looked at the changes in Lp(a) levels from baseline to week 12.

For the 60 and 240 mg arms, the Lp(a) concentration as measured by the ‘intact Lp(a) assay’ had dropped by approximately 80–85% at week 4, which remained constant until week 12. For the Apo(a) assay, the investigators observed drops of around 70–75% at week 2 for the higher dose arms, which remained constant until week 12. In addition, approximately 95% and 80% of the participants achieved Lp(a) concentrations <125 nmol/L at week 12, as was measured by the ‘intact Lp(a) assay’ and ‘Apo(a) assay’, respectively. “In the highest dose arm, we also noticed drops in other parameters at week 12, such as LDL cholesterol (-20.0%), ApoB (-17.6%), and hsCRP (15.4%). AE rates were similar between the treatment arms, around 50%; although the discontinuation rate was somewhat higher in the 240 mg arm (8.8%) compared with the placebo arm (1.5%) or the other active arms (0%).

“Muvalaplin resulted in quick and deep reductions in Lp(a) levels in patients with increased Lp(a) levels and an elevated cardiovascular risk,” summarized Prof. Nicholls. “The long-term impact of muvalaplin on Lp(a) levels and cardiovascular outcomes needs to be assessed in further studies.”

Medical writing support was provided by Robert van den Heuvel.

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