CSL’s heart attack drug ‘mega-trial’ delivers dud results

The biggest drug trial in CSL’s history, which sought to find a treatment for recurrent cardiac events, has failed to deliver the desired result.

A drug trial described by CSL as “herculean” in its ambitions has found that the compound being tested, CSL112, failed to deliver the desired result of a reduction in post-heart attack cardiac events.

CSL shares fell more than 5 per cent on the news, closing down $14.76 at $290.24 on ­Monday.

The AEGIS-II drug trial had enrolled more than 18,200 ­patients across 850 sites in 49 countries. If successful, it would have potentially resulted in a new blockbuster drug for CSL.

The trial was the largest in the history of the company, with its failure casting doubts on the way forward for more than a decade of research.

CSL told the ASX on Monday that the top-line results of the trial showed that “the study did not meet its primary efficacy endpoint of major adverse cardiovascular events reduction at 90 days. As a result, there are no plans for a near-term regulatory filing.

“Further analysis of AEGIS-II is ongoing and primary results will be presented at the American College of Cardiology Scientific Sessions to be held on April 6, and published in a peer reviewed journal.”

CSL’s head of research and development, Bill Mezzanotte, said “substantial work remains to fully analyse and then understand the complete data and then to determine any development path ahead for this asset”.

CSL said it had not factored in any contribution from CSL112 in its forward-looking financial estimates and did not expect any ­material financial impact following the conclusion of the trial.

RBC Capital Markets said the news was negative for CSL, with investors hoping for a positive outcome.

“We did not ascribe any value for CSL112 in our forecasts or valuation. Therefore, we have made no changes to our forecasts or price target,” RBC said in a note to clients.

“However, we believe there was a reasonable expectation amongst the investment community that CSL112 would be commercialised because the company has spent close to $1bn on developing and testing it, and they were also preparing their manufacturing facilities for production.

“Therefore, we expect some investor disappointment from today’s announcement.

“If CSL112 was successfully commercialised, we had expected the product would have provided a gross margin tailwind because it could have utilised some of CSL’s existing raw materials. However, that gross margin tailwind is now no longer available.”

UBS analyst Laura Sutcliffe said there was a possibility for further clinical studies to identify efficacy in smaller subgroups, but “this is rarely the outcome at this stage, in our experience’’.

“CSL112 was the next major clinical catalyst for CSL so at this point the challenge for the company may be to signpost clearly how the equity story will develop (aside from gross margin improvement in the Behring division) from here on,’’ Ms Sutcliffe said.

Just more than a year ago, CSL announced it had enrolled the final patient in the AEGIS-II trial.

“More than 10 years ago, CSL made a bold decision to study whether a plasma-derived therapy could help reduce the high risk for recurrent cardiac events that heart attack survivors experience in the first 90 days after their event,’’ the company said.

“To do this would ultimately require a cardiovascular ‘mega-trial’, and more than 18,000 heart attack survivors would have to agree to participate. After several years, and the altruistic commitment of all of our participants, the AEGIS-II trial has now enrolled the final patient.”

CSL said the trial was “the largest phase three clinical trial ever initiated in our company’s history’’.

“Testing our hypothesis on a herculean scale has relied on courage, commitment and the ­active participation of patients throughout the research process,” it said.

“The extraordinary effort to reach this stage wasn’t without hurdles. Clinical research is a team sport, and we worked across continents within CSL, with our trial partners, and with thousands of cardiology health care professionals at over 1000 study sites in nearly 50 countries.’’

CSL is scheduled to release its half-year results on Tuesday.