Alexion Pharmaceuticals Inc. reported at the 2002 Sessions of the American Heart Association some of the worst biotechnology news a company can give - preliminary data showing missed endpoints in clinical trials - but watched its stock ascend 36.5 percent Monday.
The Phase II trials, called COMMA and COMPLY, tested Alexion's pexelizumab in acute myocardial infarction patients and each had the endpoint of infarct size reduction measured at 72 hours. Although not hitting there, together the trials showed a reduction in 90-day mortality, and that is what had company officials and investors feeling bullish.
"Mortality is the gold standard of heart attack trials," said Leonard Bell, Alexion's CEO. "It has been over a decade since any trial has showed an improvement in mortality. It's unprecedented."
Alexion's stock (NASDAQ:ALXN) rose $4.05 Monday to close at $15.14.
Pexelizumab is a humanized single-chain antibody fragment that is a C5 complement inhibitor. The COMMA trial (complement inhibition in myocardial infarction treated with PTCA) split 814 acute myocardial infarction patients who received angioplasty into three roughly even arms: pexelizumab 2 mg/kg, pexelizumab 2 mg/kg followed by a 20-hour infusion of 0.05 mg/kg/hr, and placebo. The trial was conducted at 92 North American sites. The preliminary data show pexelizumab was associated with a dose-dependent and statistically significant 70 percent reduction in 90-day mortality (5.9 percent for placebo vs. 1.8 percent for pexelizumab bolus/infusion [p=0.014]).
That mortality benefit was seen at 180 days, as well. Pexelizumab bolus/infusion was associated with a 57 percent relative reduction in mortality, compared to placebo (7.4 percent placebo vs. 3.2 percent [p=0.035]). Cardiogenic shock also was lower with pexelizumab bolus/infusion (5.2 percent placebo vs. 2.8 percent), but not statistically significant (p=0.19).
Patients also received other care - about 90 percent to 95 percent in all arms received aspirin, coronary stents, IIb/III antagonists and beta blockers.
The COMPLY trial (complement inhibition in myocardial infarction treated with thrombolytics) was conducted at 87 North American sites, 22 Eastern European sites and 10 South American sites, involving a total of 920 acute myocardial infarction patients who received thrombolytics. Although there was no reduction in mortality at 90 days in the overall COMPLY population, a look at the pooled COMMA trial and the North American patients in the COMPLY trial - a total of 1,248 patients - showed that pexelizumab bolus/infusion was associated with a 55 percent reduction in 90-day mortality (6.3 percent placebo vs. 2.8 percent [p=0.019]).
Although stroke incidence was reduced in the COMPLY trial, it was not statistically significant. Overall, the drug appeared to be well tolerated in both trials.
Coming when it has - in Phase II trials - the drug has a fair amount of development road in front of it, but that doesn't diminish the positive data.
"We are very excited," Bell told BioWorld Today. "We are going to complete our analysis, confer with [partner Procter & Gamble] and look to discuss the data with the FDA." He added that the Phase II studies did what they were supposed to do - demonstrate a clearly defined dose-dependent effect - and a Phase III trial to confirm the results would be the next expected step.
Procter & Gamble Pharmaceuticals in January 1999 signed to help develop the drug in a deal with a value of up to $95 million. In December, the companies restructured the deal, giving Cheshire, Conn.-based Alexion more responsibility in the U.S. and, thus, more profit potential. Cincinnati-based P&G Pharmaceuticals, a division of Procter & Gamble Health Care, has development and commercialization rights for the rest of the world. The companies have initiated a Phase III trial of the drug in cardiopulmonary bypass patients. (See BioWorld Today, Jan. 27, 1999, and Dec. 13, 2001.)
Alexion's eculizumab is in a 300-patient Phase IIb rheumatoid arthritis trial, and Bell said the company expects to see data from it next year. The product also is being studied in membranous nephritis and lupus nephritis, as well as other indications.
But Bell said the pexelizumab data "transforms the company" and said the results could point to a "new paradigm" for treating heart disease. But he also explained the COMMA trial and its mortality reduction at three months of 5.9 percent for placebo to 1.8 percent for pexelizumab infusion/bolus was a matter of life and death.
"What that translates into, that four absolute percentage point difference, is that for every 25 patients that came into [the hospital having a heart attack], one of them survived," he said. "We are talking about people being alive."