AstraZeneca Launches Three Phase III Trials Simultaneously for Oral Small-Molecule PCSK9 Inhibitor AZD0780

▎Armstrong

On June 2, 2025, AstraZeneca registered three Phase III clinical trials for the small molecule PCSK9 inhibitor AZD0780 on the Clinicaltrials.gov website.

The first Phase III clinical trial targets HeFH, planning to enroll 405 patients, with an expected completion date of March 2027.

The second Phase III clinical trial for ASCVD is planned to enroll 2,800 patients and is expected to be completed in March 2027.

The third Phase III clinical trial targeting cardiovascular benefits for ASCVD patients plans to enroll 15,100 patients and is expected to be completed in October 2029.

AZD0780 is a small-molecule oral PCSK9 inhibitor.

AstraZeneca is also considering advancing the combination of AZD0780 and GLP-1 for weight loss and glucose reduction to achieve organ protection.

Summary

PCSK9 is the most complex target in the cardio-renal metabolism competitive landscape. In 2014, Amgen and Sanofi's PCSK9 antibodies were approved for marketing, with Amgen's Repatha achieving sales of $2.2 billion in 2024. In 2021, Novartis' PCSK9 siRNA was approved for marketing, requiring only one injection every six months, with sales reaching $333 million in Q1 2025. Merck's oral PCSK9 cyclic peptide has entered phase III clinical trials, and AstraZeneca's small-molecule PCSK9 inhibitor has also advanced to phase III clinical trials. Additionally, in vivo gene editing of PCSK9 is being actively pursued. This ultimately results in a competitive landscape where multiple drug formats, including small molecules, antibodies, siRNA, cyclic peptides, and in vivo gene editing, are competing simultaneously.