CSL's 'most ambitious' phase 3 trial ends in failure for heart attack drug

CSL Behring’s largest-ever trial has ended in failure, as the Australian pharma revealed that its cholesterol efflux enhancer was unable to reduce the risk of heart attacks.

The company had been testing CSL112, also known as apolipoprotein A-I, in a study of about 17,400 heart attack patients spread across 49 countries. The first participant was dosed in the AEGIS-II study in 2018.

But the trial failed to hit its primary endpoint of showing a reduction in the risk of major adverse cardiovascular events after 90 days when compared to placebo, CSL disclosed in a Feb. 11 release. “As a result, there are no plans for a near-term regulatory filing,” the company concluded.

CSL didn’t share many other details, although it did point out that there were no major safety or tolerability concerns with the drug. Instead, the company said it would share primary results at the American College of Cardiology Scientific Sessions in April.

“Substantial work remains to fully analyze and understand the complete data and then to determine any development path ahead for this asset,” CSL’s head of R&D Bill Mezzanotte, M.D., said in the release.

“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,” Mezzanotte added. “We plan to apply these capabilities as well as our plasma protein platform to future unmet medical need in cardiovascular and metabolic conditions as well as those in our other strategic therapeutic areas.”

CSL112 was developed using a new formulation of apoA-I, the main component of high-density lipoproteins, which was extracted from human plasma. By enhancing the body’s ability to remove cholesterol from plaque in the arteries, the hope was that CSL112 would reduce cardiovascular events among high-risk patients in what CSL had described as the “critical 90 days after a heart attack.”

When the trial was designed back in 2017, CSL executives suggested that CSL112 had “the potential to change the current treatment paradigm for heart attack survivors and improve global health outcomes for the millions of people at risk for early recurrent cardiovascular events.”

The company’s share price dropped around 5% when the Australian stock exchange opened Monday, with CSL’s shares ending the day’s trading at 290.24 Australian dollars compared to a Friday closing price of AU$305.