WASHINGTON, Jan. 2 (UPI) -- Alexion appears to have killed the development of pexelizumab due to disappointing phase 3 results indicating the heart-attack drug is no better than placebo.
The impact of the news, which appears in the Jan. 3 issue of the Journal of the American Medical Association, may be slight because the results have previously been released by Alexion, which had been developing pexelizumab in collaboration with Proctor & Gamble.
Experts say that although this is the end of pexelizumab, the concept of using an anti-inflammatory to treat a specific kind of heart attack known as acute ST-elevation myocardial infarction, or STEMI, is still very much alive.
"I think it does mean an end for this drug, but not an end for the concept," Paul Armstrong of the University of Alberta and lead investigator of the trial told United Press International.
"The flip side of these things is that it opens up new opportunities for contenders to the throne," Armstrong added. "And this area for inflammation as it relates to how big heart attacks are and what are the consequences is still an untapped frontier."
One possible contender, he said, is an agent called MC-1 that is being developed by Medicure. The drug is currently in a trial involving patients with coronary bypass, and Armstrong is serving as a scientific consultant to the company.
In the pexelizumab study, which was known as the APEX AMI trial and involved 5,745 STEMI patients, Armstrong and colleagues evaluated infusion of the drug in conjunction with reperfusion procedures, such as angioplasty or stent placement.
No difference was detected in the rate of death at 30 or 90 days between the pexelizumab group and the placebo group. Both groups had a low death rate (3.92 percent in the placebo arm at 30 days versus 4.06 percent in the pexelizumab group). Rates of cardiac shock and heart failure were also similar between the two groups.
Although the pexelizumab results were disappointing, "the good news is that the mortality was the lowest ever reported in a trial of this magnitude," Armstrong said. This means that if patients are rapidly treated with currently available therapies, they may fare better than previously thought.
However, there's still a substantial unmet need in this setting, so Armstrong's group is working on developing strategies for getting treatments to patients faster. This includes possibly teaching paramedics how to recognize this condition, using new technology to transmit electrocardiograms from the field so a physician at a remote site can help make the diagnosis.
This could allow clotbusters, such as fibrinolytics, tenectaplase and tPA, to be delivered earlier, which may avoid heart-muscle damage altogether, Armstrong said.
John Eikelboom of McMaster University in Hamilton, Ontario, Canada, who co-authored an editorial in JAMA, told UPI he agreed that the concept of using anti-inflammatories was still a potentially viable strategy.
"The trial results probably mean the end of pexelizumab," Eikelboom said. "It would be difficult for it to find a niche in practice," he said.
However, Eikelboom added, "I don't think the concept can now be dismissed." There are still questions that remain unanswered, such as whether pexelizumab acted on the right target and whether there might be more effective ways of developing a potential drug.
Other anti-inflammatories in development that may have potential include an inhibitor of C-reactive protein and drugs that target white blood cells, Eikelboom said.
Stephen Squinto, Alexion's executive vice president and head of research, told UPI pexelizumab was essentially a dead program.
"We don't think we intended to take this drug forward," Squinto said. He noted that the phase 3 results have been publicly disclosed two previous times, the most recent being at the American Heart Association meeting in November.
Alexion will now focus its attention on Soliris, a potential treatment for a rare, life-threatening blood disease called paroxysmal nocturnal hemoglobinuria. The company has filed for approval in both the United States and Europe and hopes to launch in 2007, Squinto said.