Big news for your heart and your genes! A groundbreaking experimental drug called lepodisiran, developed by Eli Lilly, might soon revolutionize preventive cardiology for millions of people carrying a genetic bombshell: high lipoprotein(a), or Lp(a). Unlike regular “bad” LDL cholesterol, Lp(a) is mostly dictated by your DNA and has been untreatable — until now. In a new Phase 2 clinical trial, a high dose of lepodisiran — delivered through just two shots — dropped Lp(a) levels by a staggering 95%, with effects lasting up to a year. Scientists are buzzing, and Phase 3 trials are racing forward. Could this siRNA-based drug be the secret weapon in the fight against genetic heart disease? Stay tuned — this could be the cholesterol slayer we’ve been waiting for.

Key Points:

• Lepodisiran is an experimental siRNA-based drug from Eli Lilly designed to target and reduce lipoprotein(a), or Lp(a), a genetically inherited cholesterol linked with a higher risk of heart disease.
• Lp(a) levels are resistant to traditional lifestyle changes or existing medications, affecting an estimated 20% of the global population.
• In the Phase 2 ALPACA trial involving 320 participants, high doses of lepodisiran reduced Lp(a) levels by up to 95% after one year — the highest reduction ever recorded for this cholesterol type.
• The drug works by silencing the production of apolipoprotein(a) in the liver using small interfering RNA (siRNA) technology.
• “It’s remarkable,” said Dr. Eric Brandt of the University of Michigan’s Frankel Cardiovascular Center. “These drugs have the potential to nearly eliminate that lipoprotein.”
• No serious adverse reactions were reported, and the drug showed a good safety profile across dosages.
• This success echoes the rise of other siRNA-based therapies, such as Leqvio (by Alnylam Pharmaceuticals and Novartis), which was FDA-approved in 2021 to lower LDL cholesterol in specific patients.
• A Phase 3 trial for lepodisiran is already underway, aiming to confirm these promising results in a larger group and potentially bring this drug closer to FDA approval.

If lepodisiran passes upcoming trials, it could become the first effective treatment for genetically elevated Lp(a), dramatically reshaping how physicians manage inherited cardiovascular risk.
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