CSL Limited’s AEGIS-II trial of CSL112 fails to meet primary endpoint in heart attack patients

CSL Limited (ASX:CSL; USOTC:CSLLY), a renowned global biotechnology leader, disclosed the top-line outcomes from its eagerly anticipated Phase 3 AEGIS-II trial. This pivotal study assessed the efficacy and safety of CSL112 (Apolipoprotein A-I [human]) against placebo in diminishing the risk of major adverse cardiovascular events (MACE) among patients recovering from an acute myocardial infarction (AMI). Contrary to expectations, the study did not achieve its primary efficacy endpoint related to MACE reduction at the 90-day mark. Consequently, CSL Limited has indicated that it does not intend to pursue near-term regulatory filings based on these results.

In light of these findings, C. Michael Gibson, M.S., M.D., of the Baim Institute for Clinical Research and Harvard Medical School, and the lead investigator for the AEGIS-II trial, stated, “We look forward to sharing our scientific learnings regarding cholesterol efflux and recurrent cardiovascular events. We will continue to analyze the findings and share the full results in the coming months.” This statement underscores the commitment to further research and understanding of the complex interactions between cholesterol management and cardiovascular health.

The AEGIS-II trial represents a significant effort in cardiovascular research, involving over 18,200 participants across more than 850 sites in 49 countries. This large-scale, multicenter, double-blind, randomized, placebo-controlled study was designed to evaluate CSL112’s role in reducing recurrent cardiovascular events during the critical 90-day period following a heart attack. Despite the setback, the trial’s comprehensive data will be invaluable for ongoing scientific exploration.

Dr. Bill Mezzanotte, Executive Vice President and Head of R&D at CSL, reflected on the trial’s implications: “AEGIS-II is the most ambitious study in our company’s history, and we are proud of the quality of the study we delivered and the enhanced capabilities we developed to do so.” He emphasized the intention to leverage these capabilities for addressing future unmet medical needs in cardiovascular and metabolic conditions, as well as in other strategic therapeutic areas.

Investors and stakeholders have been reassured that the outcome of the AEGIS-II trial does not pose a material financial impact on CSL Limited, as potential contributions from CSL112 had been excluded from the company’s forward-looking estimates. The full analysis and results of the AEGIS-II trial are eagerly awaited by the scientific community, with primary results set to be presented at the American College of Cardiology Scientific Sessions on April 6, 2024, and subsequent publication in a peer-reviewed journal.

This development in the AEGIS-II trial highlights the complexities and challenges inherent in advancing cardiovascular therapeutics. CSL Limited’s commitment to continued research and development, despite this setback, exemplifies the pharmaceutical industry’s persistent pursuit of innovative solutions to improve patient outcomes in the face of heart disease.

The outcome of the AEGIS-II trial, while disappointing, is a critical step in the ongoing journey to understand and combat cardiovascular disease. It underscores the importance of rigorous clinical testing and the need for continued innovation in the field. The comprehensive data collected during this trial will provide valuable insights that can fuel future research, potentially leading to new breakthroughs in cardiovascular health. CSL Limited’s dedication to analyzing these results and applying lessons learned to future projects is commendable and will undoubtedly contribute to the advancement of medical science in this vital area.