MELBOURNE, Australia — A way to boost good cholesterol and avert repeat heart attacks, which has eluded two of the world's biggest drugmakers, may have been sitting in CSL's trash.
The Australian company realized that instead of discarding unused blood components left over from making hemophilia, burns and immune-system treatments, it could extract the beneficial cholesterol known as HDL and infuse it into patients. The idea is that HDL therapy may quell inflamed arteries and dissolve the life-threatening plaques that clog them, said Andrew Cuthbertson, CSL's chief scientist.
The experimental treatment was the focus of three papers at the American Heart Association's scientific meeting in Dallas Wednesday. Mid-stage studies showed a "dramatic and rapid increase" in key indicators of the process in which bad cholesterol, or LDL, is flushed from patients' arteries.
"If this works, we could save a lot of lives and it could be very good for the company commercially," Cuthbertson said in an interview. "It's a big priority for us."
The treatment is Melbourne-based CSL's first foray into cholesterol-lowering drugs, a global market IMS Health valued at $33.6 billion last year. The product, if approved following successful further studies, may garner annual sales of as much as $500 million in its first five years, according to UBS AG.
"It's a huge market," said Andrew Goodsall, a health-care analyst with UBS in Sydney, who recommends investors buy CSL shares. "For a lot of investors, this is a point of excitement."
Rapidly repairing clogged and inflamed arteries could save lives. About a quarter of patients die and half are re- hospitalized in the year after a heart attack, a U.S. study presented in May found.
Traditional cholesterol-lowering medicines, or statins, such as AstraZeneca Plc's Crestor, don't act fast enough to protect patients in the first weeks after a heart attack, when plaque in other locations risks dislodging and causing deadly clots, said Philip Aylward, a cardiologist at the South Australian Health and Medical Research Institute in Adelaide who will lead further clinical studies of the CSL product in Australia. HDL-based therapy may offer more promise, according to Aylward.
"We think that if you can neutralize that inflammatory and active process than you may produce benefits fairly quickly," he said in an interview.
Wednesday's presentations described results of a phase 2a study that evaluated the effects of a single-dose of the CSL compound, called CSL112, in 44 patients with stable heart disease over 90 days. In addition to positive results for key biological indicators, the trial data also showed the product was safe and well tolerated, even when patients took other blood thinners, the company said.
CSL aims to start a phase 2b study in the first half of 2014, according to Cuthbertson. That trial will compare weekly doses of CSL112 with a placebo over four weeks in about 1,200 heart-attack patients in the U.S., Europe, Japan and Australia. Results of the research, which will cost about $60 million to $70 million, may be ready by late 2015, he said.
"Everything we have seen so far encourages us to take the next step," Cuthbertson said. "That's where the rubber will hit the road because we're looking at real clinical endpoints like death and second heart attack."
Other medicines designed to raise levels of good cholesterol, which ferries fatty lipids out of the arteries, have failed at a more advanced stage.
Roche Holding AG halted research on a drug known as dalcetrapib in the final stage of clinical tests in May 2012. The product belonged to a class of heart medicines that inhibit a molecule known as CETP, which results in higher levels of good cholesterol. But it also turned out to boost blood pressure and inflammation. Pfizer Inc. dropped its own experimental medicine torcetrapib in December 2006, also in the last stage of human tests, because it raised blood pressure and patients died during the study.
Previous research has shown that synthetic HDL can reverse plaque buildup in the arteries when it is infused, said John Gordon Harold, president of the American College of Cardiology. The benefit disappears once the infusions stop, and researchers haven't been able to convert the therapy into an oral medication that would be easier to use.
"This is an early study suggesting there may be some benefit, but you can't say much more than that," Harold, a cardiologist at the Cedars-Sinai Heart Institute in Los Angeles, said in an interview. "It needs further study."
Research with other medications that affect HDL levels hasn't been encouraging, he said.
"Almost all the studies to date have been either neutral or negative," Harold said. "The HDL hypothesis has been put into question."
The stumbling block to date has been the absence of a drug that can mimic the cholesterol-extracting effect of HDL in a way that benefits heart patients, said Bronwyn Kingwall, head of the metabolic and vascular physiology unit at Melbourne's Baker IDI Heart and Diabetes Institute.
"It's a relationship we have known about for decades, but we haven't had the means to exploit it therapeutically," she said in an interview.
CSL isn't the only company still trying. Nor is it the most advanced. Merck & Co. and Eli Lilly & Co. are developing alternative compounds, with late-stage studies slated for completion from 2015 to 2017, Kingwall said in a review paper published in the journal Circulation earlier this year.
Cerenis Therapeutics SA of France began a mid-stage study of a recombinant drug designed to mimic HDL particles in March 2011. The results will be presented in early 2014, said Jean- Louis Dasseux, the company's president and chief executive. The drug has been shown to reduce plaque in as soon as one month in HDL-deficient patients, Dasseux said. The search for a potential partner is proceeding, he added.
A drug would have to show a reduction of about 15 percent in subsequent heart attack or stroke to be considered clinically meaningful, according to Kingwall. It would also have to be tested in a study of about 15,000 patients that would cost $250 million to $300 million, she said.
CSL has the option of developing CSL112 alone or with another company with expertise in acute cardiovascular medicine, Cuthbertson said. Any partnering discussions would probably be held during the next two years, he said.