Isis Pharmaceuticals CEO Stanley Crooke gets asked a lot about mipomersen, a drug his company is developing to treat dangerously high cholesterol in the blood. It is Isis’s (NASDAQ: ISIS) lead drug candidate and generated a huge partnership with Genzyme worth $325 million in cash upfront, with a lot more to come if this drug pans out in further clinical trials.
Instead of doing the umpteenth interview on that subject, I asked Crooke about other stuff emerging in the Isis pipeline when I stopped by his company’s Carlsbad, CA, offices a couple weeks ago. He looked at me like it was a little odd, but he happily dived in for a discussion about a lesser-known stepchild in the Isis pipeline, called Isis 353512. It’s designed to block a marker of heart disease and other inflammatory conditions, called C-reactive protein.
“This question reminds me a lot of the cholesterol debates 40 years ago,” Crooke says.
Like with those arguments about cholesterol, medical researchers want to know whether the C-reactive protein found in the blood of patients with heart disease is a bad actor that spurs inflammation in vessel walls that can lead to heart attacks, or whether it’s a bystander, Crooke says. The answer has been difficult to pin down because conventional drugs can’t be designed to hit the C-reactive protein. Doctors can already run diagnostic tests of the marker to assess heart disease risk, yet they don’t know whether blocking it can actually lower the risk of heart attacks, or help treat inflammatory diseases like Crohn’s or rheumatoid arthritis, Crooke says. The Isis drug, like all of the company’s candidates in clinical trials, uses proprietary antisense technology to bind specifically with the RNA of the target protein, so it can block the target at its origin in the liver, Crooke says.
The question will be whether that really matters much for patients. Isis is banking on research that shows C-reactive protein is associated with cardiovascular disease patients getting worse, which suggests they may get better if the inflammatory molecule is mopped up. Animal studies of the Isis compound showed it could significantly suppress the protein in the blood and liver.
Isis is currently testing the drug in an early-stage safety study, but it clearly intends to get an answer that will give it confidence to spend money on the kind of bigger trials needed to settle the debate. It is currently testing the drug in a placebo-controlled, randomized study of 58 healthy volunteers to see if it can bring down C-reactive protein levels at a variety of doses. The study is expected to be completed in September 2009—just in time to become fodder for the fall slate of medical meetings next year.
“This is the only drug specific enough to work,” Crooke says. “No other approach has come close to being successful.” He sure makes it sound like he relishes the idea of being first to answer this question. “This is Isis. We lead, not follow.”