Phase 2b results of oral PCSK9 inhibitor in hyperlipidemia
ACC.25 – In the phase 2b PURSUIT trial, AZD0780, an investigational oral small molecule PCSK9 inhibitor, reduced LDL-c by up to 50.7% at 12 weeks in patients with hyperlipidemia, compared with placebo.
This summary is based on the presentation of Michael Koren, MD (Jacksonville, FL, USA) at the ACC.25 Scientific Session - Efficacy And Safety Of Azd0780, An Oral Small Molecule Pcsk9 Inhibitor For Treatment Of Hypercholesterolemia: Results From A Ph2b Randomized Placebo-controlled Clinical Trial.
Introduction and methods
A significant proportion of patients with ASCVD do not achieve their LDL-c targets in clinical practice. There is a need for effective oral lipid-lowering therapies. The phase 2b PURSUIT trial evaluated the safety and efficacy of a novel oral small molecule PCSK9 inhibitor versus placebo in hyperlipidemia.
PURSUIT was a global, randomized, double-blind, placebo-controlled multicenter study in which 428 patients with hypercholesterolemia (defined as fasting LDL-c ≥70 mg/dL [1.8 mmol/L] and <190 mg/dL [4.9 mmol/L]) on stable dose of moderate- or high-intensity statins were randomized in a 1:1:1:1:1 ratio to once daily AZD0780 (1 mg, 3 mg, 10 mg or 30mg) or matching placebo for 12 weeks. 426 patients started treatment. The primary endpoint was the percent change in LDL-c from baseline to week 12.
Main results
- At 12 weeks, treatment with AZD0780 significantly reduced LDL-c compared with placebo (placebo-corrected difference in the 30 mg arm: -50.7%; 95%CI: -59.0 to -42.4).
- AZD0780 also reduced total cholesterol, non-HDL-c, and apoB compared with placebo (placebo-corrected differences were 29.4%, 45.2%, and 39.9%, respectively).
- The median reduction in Lp(a) was -19.5% (95%CI: -27.3% to -11.7%) with AZD0780 30 mg.
- At the 30 mg dose, 84.2% of patients achieved the LDL-c target of <70 mg/dL. In the placebo group, only 13% of patients achieved this target.
- Any adverse events occurred in 38.2% of the patients in the AZD0780 groups and in 32.6% of the patients in the placebo group.
Conclusion
In the phase 2b PURSUIT trial, treatment with AZD0780 led to robust, dose-dependent, placebo-corrected reductions in LDL-c from baseline to 12 weeks, with a favorable safety and tolerability profile.
- Our reporting is based on the information provided at the ACC.25 Scientific Session -