Eli Lilly and Company (NYSE: LLY) has announced remarkable results from its Phase 2 ALPACA study, showing that lepodisiran, an investigational small interfering RNA (siRNA) therapy, can achieve a 94% reduction in lipoprotein(a) [Lp(a)] levels—a key genetic risk factor for heart disease. This heart disease risk reduction was observed in adults with elevated Lp(a) over a 60 to 180-day period, making lepodisiran a potential medical breakthrough in cardiovascular innovation.

The study demonstrated that the highest dose (400 mg) of lepodisiran resulted in an average 93.9% reduction in Lp(a) levels, meeting the primary study endpoint. Additionally, participants receiving the 16 mg and 96 mg doses of lepodisiran experienced reductions of 40.8% and 75.2%, respectively.

Groundbreaking Results in Heart Health

The ALPACA trial showed that lepodisiran produced significant and sustained Lp(a) reductions. Those receiving the highest dose (400 mg) experienced a 94.8% reduction in Lp(a) levels at day 180, with a 91.0% reduction still evident after one year (day 360). At day 540, nearly 1.5 years later, Lp(a) levels remained 74.2% below baseline. This extended reduction is particularly important for individuals at high risk for heart disease, as elevated Lp(a) levels can significantly increase the likelihood of cardiovascular events such as heart attacks and strokes.

The data also revealed reductions in apolipoprotein B (apoB), another key cholesterol marker, showing the broader potential of lepodisiran in improving heart health. The highest dose (400 mg) led to a 14.1% and 13.7% reduction in apoB at day 60 and day 180, respectively.

Addressing the Need for Cardiovascular Innovation

Elevated Lp(a) affects approximately 20% of Americans, increasing their risk for heart disease, stroke, and heart valve issues like aortic stenosis. Currently, there are no approved treatments specifically targeting high Lp(a), and lifestyle changes such as diet and exercise have limited impact on reducing Lp(a) levels. Lilly’s lepodisiran offers a promising solution for this unmet need, potentially revolutionizing the approach to heart disease prevention and treatment.

Steven Nissen, M.D., Chief Academic Officer of the Heart, Vascular & Thoracic Institute at the Cleveland Clinic, stated, "The significant and sustained reductions in Lp(a) levels seen with lepodisiran are incredibly promising. This cardiovascular innovation could offer a durable solution for patients with genetically elevated Lp(a), ultimately reducing their heart disease risk in the long term."

A New Hope for Heart Disease Risk Reduction

Lepodisiran works by inhibiting the production of apolipoprotein(a) (apo[a]), a key component of Lp(a). By doing so, it has the potential to significantly lower cardiovascular risk for individuals affected by elevated Lp(a). Ruth Gimeno, Group Vice President at Lilly, remarked, "These exciting results underscore our commitment to advancing heart health and genetic medicine. We’re hopeful that lepodisiran will provide a long-term solution for individuals at high risk for heart disease."

The company is currently conducting the ACCLAIM-Lp(a) Phase 3 clinical trial, which aims to evaluate the ability of lepodisiran to reduce cardiovascular events in patients with elevated Lp(a).

Safety and Side Effects

The Phase 2 trial reported that treatment-emergent adverse events (TEAEs) were generally mild, with 12% of patients receiving the 96 mg dose and 14% receiving the 400 mg dose experiencing side effects. Importantly, no serious adverse events related to lepodisiran were reported, and no patients discontinued treatment due to drug-related issues. One death occurred in the 16 mg group due to unrelated complications from chronic coronary disease.

About ALPACA

The Phase 2 ALPACA study was a randomized, double-blind, placebo-controlled trial that investigated the safety and efficacy of three different doses of lepodisiran (16 mg, 96 mg, and 400 mg). The trial included 320 participants and assessed Lp(a) reduction over a period of up to 18 months.

About Eli Lilly and Company

Eli Lilly and Company has been a leader in medical innovation for nearly 150 years, with a strong commitment to advancing treatments for major global health challenges. Lilly’s groundbreaking work in cardiovascular medicine, including the development of lepodisiran, reflects its dedication to improving heart health and providing long-term, durable treatments for patients at high risk of heart disease.

For more information, visit Lilly.com or follow the company on social media.

Forward-Looking Statements

This press release contains forward-looking statements about lepodisiran’s potential to reduce heart disease risk and its ability to prevent cardiovascular events. As with any drug development, there are risks and uncertainties, and there is no guarantee that the ongoing studies will achieve the same results or that lepodisiran will be approved for use.