HQ Team
November 19, 2024: Eli Lilly announced promising results from its Phase 2 clinical trial of muvalaplin, an oral medication designed to lower lipoprotein(a) or Lp(a) levels, a genetically inherited form of high cholesterol, a risk factor for cardiovascular disease.
Known as the KRAKEN trial, in the second phase results, muvalaplin significantly reduced elevated Lp(a) levels in adults, by 70 per cent in a conventional blood test and a more scientific and advanced method showed an improvement of 86 per cent.
Findings
The trial involved 233 participants with high Lp(a) levels, defined as greater than 175 nmol/L, and conditions such as atherosclerotic cardiovascular disease, Type 2 diabetes, or familial hypercholesterolemia. Participants were randomly assigned to receive muvalaplin at doses of 10 mg, 60 mg, or 240 mg daily for 12 weeks or a placebo. Results showed that muvalaplin treatment led to significant reductions in Lp(a) levels compared to placebo.
The highest dose of muvalaplin (240 mg) achieved an impressive 85.8% reduction in Lp(a) levels. Notably, the study revealed that approximately 97% of participants receiving the higher doses achieved Lp(a) levels below the critical threshold of 125 nmol/L, indicating a substantial potential for reducing cardiovascular risk. The reductions in apolipoprotein B (apoB), another key component associated with heart disease, were also statistically significant across all tested doses.
Critical need
High levels of Lp(a) are known to double or triple the risk of heart attacks and strokes, affecting about 20% of the population globally, particularly individuals of African and South Asian descent. Currently, there are no FDA-approved medications specifically targeting Lp(a), making muvalaplin a notable advancement in cardiovascular treatment options. Stephen J. Nicholls, MBBS, Ph.D., director of the Victorian Heart Hospital and Institute, emphasized the importance of these findings: “Current cholesterol-lowering therapies are not approved to lower Lp(a) levels, highlighting an unmet need for people living with cardiovascular disease.”
Safety
The KRAKEN trial also assessed the safety profile of muvalaplin. Adverse events were reported similarly between the muvalaplin and placebo groups, with treatment-emergent adverse events occurring in about 14.9% of the placebo group compared to lower rates in the muvalaplin groups (5.9% for 10 mg, 14.3% for 60 mg, and 14.7% for 240 mg).
Ruth Gimeno, Ph.D., group vice president at Lilly Research Laboratories, expressed enthusiasm about the results: “While injectable approaches for Lp(a) are currently in Phase 3 development…these are the first positive Phase 2 data for an oral approach.” She noted that further studies are necessary to determine whether lowering Lp(a) translates into fewer cardiovascular events.
Future
The encouraging results from this trial position muvalaplin as a potential game-changer in managing cardiovascular risk associated with high Lp(a) levels.
Eli Lilly is now considering next steps for advancing muvalaplin into late-stage trials while continuing discussions with regulatory authorities.
