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a little perspective is in order. ZymoGenetics and its partner halted a final-stage clinical trial of 200 patients who took atacicept for lupus of the kidneys back in October, because it appeared to raise a risk of severe infections when used in combination with another immune-suppressor. But that effect appeared to be isolated to that trial, Williams says, and the companies continued to run other clinical trials of atacicept for patients with rheumatoid arthritis, multiple sclerosis, and lupus that circulates through the body (systemic lupus erythematosis).
Why keep going? ZymoGenetics says the evidence from animal trials and early human studies suggests that blocking both BLyS and APRIL ought to produce a more potent shutdown of inflammation that lupus patients need, Williams says. That translates to the potential for lower doses, possibly less frequent doses, and therefore higher profit margins than its rival, Human Genome Sciences.
The big test of this hypothesis is an ongoing 510-patient study that compares two different doses of atacicept with a placebo. ZymoGenetics is increasingly hopeful that this trial, which is expected to run into 2011, will be a success. Zymo is bullish because it is enrolling similar types of patients as the trial from Human Genome Sciences (people with evidence of inflammation in the blood, and who are actively suffering flare-ups) and it is designed to measure the same clinical goal, or endpoint, as its rival. Many past trials have failed because of vagueness around how to measure the activity of the disease, and how to really classify people as sufferers of lupus, which is hard to diagnose. Full details on how Human Genome Sciences did it are expected to be presented this fall at the American College of Rheumatology meeting.
Most patients with lupus have traditionally been given more blunt, shotgun-style immune-suppressors, like corticosteroids, rather than a more targeted approach against a particular target, like Human Genome Sciences and ZymoGenetics/Merck Serono are using.
ZymoGenetics spent years talking up the potential of atacicept, before it was de-emphasized and farmed out last fall to Merck Serono. But yesterday, Williams reminded me that the company sees wide-ranging potential against inflammation for this drug, just as his former company, Immunex, once did for etancercept (Enbrel), which is now the world’s best-selling biotech drug with more than $7 billion in annual worldwide sales. That drug famously failed in its first major clinical trial for patients with severe sepsis, before it hit the jackpot in rheumatoid arthritis and branched out into other related autoimmune diseases. He’s hopeful history will repeat itself with atacicept.