CSL Heart Attack Hopeful Fails to Meet Primary Endpoint in Phase III Trial

CSL_iStock, josefkubes

Pictured: CSL's building in Prague, Czech Republic/iStock, josefkubes

CSL on Sunday announced that its investigational cholesterol efflux enhancer CSL112 failed the Phase III AEGIS-II trial, unable to significantly improve outcomes in patients who had suffered a heart attack.

The company did not provide specific data in its announcement but said that CSL112 did not significantly reduce major adverse cardiovascular events versus placebo at 90 days after an acute myocardial infarction episode.

AEGIS-II did detect any major safety or tolerability issues with CSL112. However, CSL no longer has near-term plans to seek regulatory approval for the candidate, according to its announcement.

CSL’s stock dipped around 5% on Monday in response to the late-stage failure.

Bill Mezzanotte, executive vice president and head of R&D at CSL, in a statement called AEGIS-II the “most ambitious study” in the company’s history, adding that it will continue to analyze the findings to better understand the data and “determine any development path ahead for this asset.”

“We are proud of the quality of the study we delivered and the enhanced capabilities we developed to do so,” Mezzanotte said. “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."

CSL intends to present results from AEGIS-II at the upcoming American College of Cardiology Scientific Sessions in April 2024.

AEGIS-II is a randomized, double-blinded, parallel-group and placebo-controlled study that enrolled 18,200 patients across nearly 50 countries, making it CSL’s largest-ever trial. The study was first announced in December 2017 and dosed its first patient a few months later in March 2018.

At the time, CSL CSO Andrew Cuthbertson said 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.”

CSL112 is CSL’s novel and proprietary formulation of the plasma-derived protein apolipoprotein A-I, which is the main component of high-density lipoprotein and is an important player in regulating cholesterol levels. The candidate works by boosting the body’s natural capability to remove cholesterol from plaques and carrying them to the liver for detoxification.

In November 2016, CSL announced positive data from the Phase IIb AEGIS-I study showing that CSL112 was safe overall and did not trigger “significant changes in liver or kidney function.” The mid-stage trial also underscored its tolerability in acute myocardial infarction patients and validated its mechanism of action, demonstrating an up to four-fold jump in cholesterol efflux capacity versus baseline.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

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