A basic search of scientific literature says that Cambridge, MA-based Acceleron Pharma is trying to do something that won’t work. Past experiments suggest that a drug like its lead candidate is more likely to cause people to get anemia, not help treat it.
But Acceleron has witnessed the unexpected in small human studies, and it’s a big reason why this little company says its drug, ACE-011, has a shot to challenge the dominant player in the $11.5 billion worldwide anemia market, Thousand Oaks, CA-based Amgen (NASDAQ: AMGN).
“This has the opportunity to completely reverse the conventional wisdom in anemia,” says Steve Ertel, Acceleron’s vice president of corporate development. Adds CEO John Knopf: “Now there’s a lot of interest, but it was such an unexpected finding.”
Anemia is one of the first diseases that really benefitted from the biotech revolution, when Amgen created the first genetically engineered version of the erythopoeitin protein 20 years ago to stimulate the body to make more red blood cells. This business has become so big that Amgen lost $29 billion of stock market value in 2007 after its two anemia drugs were tied to a higher risk of heart attack, stroke, and death when used at high doses. Still, the drugs are considered critical tools in the modern treatment of patients with various states of kidney disease, and cancer patients who get anemia from chemotherapy.
Amgen’s drugs are injectable, and a number of competitors over the years have tried another route of treating anemia with oral pills that block enzymes, which is supposed to enable the body to regain its natural ability to produce red blood cells. San Francisco-based Fibrogen, GlaxoSmithKline, and San Diego-based Palkion are a few of the companies trying to develop drugs that interfere with these HIF prolyl hydroxylases.
Acceleron’s ACE-011 is completely different. It’s a genetically engineered protein that’s made to block a protein on cells known as the activin receptor type IIa. The main idea is that by hitting this target, the drug is supposed promote bone formation, which ought to be helpful for cancer patients who suffer from bone density loss. Past research has suggested it’s involved in red blood cell growth, so blocking it might cause people to become anemic, or so the thinking went, Knopf says.
What Acceleron found in its first clinical trial was that its drug appeared to improve bone formation like it was supposed to. But it had the opposite effect on red blood cells than would have been predicted. One single dose at the highest dose tested in the trial showed ACE-011 was basically like giving patients a transfusion with three full units of blood, without provoking any of the worrisome safety signals that the FDA has warned doctors about with high doses of the anemia drugs made by Amgen.
“No one really questions that it’s working,” Ertel says of the Acceleron drug.