American College of Cardiology’s (ACC) Annual Scientific Session & Expo | Chicago | News | Updates

AZD0780, a New Oral PCSK9 Inhibitor, Shows Strong LDL-C Lowering Effects in Phase IIb PURSUIT Study

AZD0780, a once-daily oral PCSK9 inhibitor currently under investigation, is being developed for individuals who fail to meet their LDL-C goals despite conventional lipid-lowering treatments like statins. The Phase IIb PURSUIT clinical trial showed that patients who received AZD0780 in addition to their regular statin regimen experienced a statistically meaningful reduction in LDL-C levels compared to those given a placebo.

Over a 12-week treatment period, daily administration of 30mg AZD0780 — taken without any dietary or fasting restrictions — resulted in an average LDL-C decrease of 50.7%. This reduction was consistent across participants, regardless of whether they were on moderate- or high-intensity statin therapy at the start of the trial.

Furthermore, 84% of those treated with AZD0780 achieved the LDL-C level recommended by the American Heart Association and American College of Cardiology (below 70 mg/dL), compared to just 13% of those receiving only background statin treatment.

Elevated LDL-C levels, typically 70 mg/dL or higher, represent a major cardiovascular risk factor, contributing to conditions like heart attacks and strokes. Despite the availability of various lipid-lowering therapies, over 70% of patients worldwide are still unable to reach the target LDL-C levels recommended by medical guidelines.

In terms of safety, AZD0780 was well tolerated overall. The rate of adverse events was similar between patients taking the active drug (38.2%) and those on placebo (32.6%).

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Lilly’s Experimental Therapy Lepodisiran Shows Dramatic Reduction in Lipoprotein(a), a Key Genetic Risk Factor for Heart Disease

Eli Lilly has reported encouraging data from its Phase 2 clinical trial of lepodisiran, an investigational small interfering RNA (siRNA) drug aimed at lowering lipoprotein(a), or Lp(a)—a genetic contributor to cardiovascular disease. The study, known as ALPACA, revealed that lepodisiran led to a striking decrease in Lp(a) levels, with the highest tested dosage (400 mg) delivering an average reduction of nearly 94% from baseline during the 60 to 180-day post-treatment window.

The trial evaluated several dose levels of lepodisiran, each administered twice—once at the start of the study and again at day 180. A separate group received a 400 mg dose at baseline followed by a placebo at day 180. Those given the lower doses of 16 mg and 96 mg saw Lp(a) reductions of 40.8% and 75.2%, respectively, over the same time frame.

Beyond meeting its primary objective, lepodisiran also achieved key secondary goals. Substantial and sustained reductions in Lp(a) were recorded across nearly all timepoints measured throughout the 18-month study period. Among participants who received two 400 mg doses, Lp(a) levels dropped by an average of 94.8% between day 30 and day 360. At the one-year mark (day 360), Lp(a) levels remained 91% below their starting point, and at roughly 18 months (day 540), the reduction was still a significant 74.2%.

The therapy also had an impact on apolipoprotein B (apoB), a cholesterol-related marker associated with cardiovascular risk. At the highest dosage, apoB levels dropped by 14.1% at day 60 and 13.7% at day 180. These reductions were maintained through the end of the study following a second 400 mg dose.

As for safety, treatment-emergent side effects linked to the drug were relatively infrequent. One participant (1%) in the placebo group experienced an adverse event, compared to 3% in the 16 mg group, 12% in the 96 mg group, and 14% in the group receiving 400 mg doses.