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By Bill Berkrot and Ransdell Pierson
WASHINGTON, March 30 (Reuters) - A new type of heart drugbeing developed by GlaxoSmithKline, which failed themain goal of a Phase III study of patients with chronic butwell-treated heart disease, showed signs of potential benefit,the trial's co-leader said.
The results presented at the American College of Cardiology(ACC) scientific meeting in Washington on Sunday provided aglimmer of hope that the medicine, darapladib, may have value.
"I'm convinced there is a signal here of efficacy and thedrug is safe," said Dr. Harvey White, co-chair of the large,Glaxo-sponsored international study, who presented the findings.
The real test of darapladib is likely to come from a second,late-stage study in far less stable patients who received themedicine within 30 days of a heart attack.
A positive result in that study could put the drug back ontrack, after it was largely discounted by analysts and investorsfollowing the first Phase III failure.
The stakes are high for the British drugmaker as gainingfull control of darapladib was one of the reasons behind its$3.6 billion acquisition of Human Genome Sciences in 2012.
Human Genome had rejected an earlier $2.6 billion offer,claiming that Glaxo was underestimating the blockbuster salespotential of darapladib.
Glaxo had previously said darapladib did no better than aplacebo in decreasing the risk of a combination ofcardiovascular death, heart attack and stroke in the trialcalled Stability. The trial involved 15,828 patients followedfor a median of 3.7 years.
For those taking the Glaxo pill, 9.7 percent had one of themajor adverse events compared with 10.4 percent for the placebo,which was not a statistically significant difference.
"The question is whether or not a population of patients athigher risk may yield different results," said Dr. PatrickO'Gara, the incoming ACC president from Brigham & Women'sHospital in Boston who was not involved in the study.
"I don't think that we as a community are ready to throw itaway. Further investigation would be appropriate," added O'Gara,who called the Stability trial spectacularly well done. "We'rehopeful that something like this may be a breakthrough."
A lack of any impact on stroke prevention appears to havecontributed to the failure of the study, researchers surmised.
In addition, the effect of the Glaxo drug may have beenmuted by the high level of care the patients were receiving.
Almost all were taking statins and aspirin and nearly 80percent were on blood pressure drugs - all known to decrease therisk of heart attacks, strokes and death.
"We're setting a very high bar and we may have affected ourability to (determine) a treatment effect," said White, directorof the coronary care unit at Auckland City Hospital in NewZealand.
SECONDARY GOALS IMPORTANT
The drug's impact on the secondary goals of the study wasdeemed "nominally significant" by researchers, meaning they sawthe potential of a clinically meaningful effect despite fallingshort of statistical significance.
One of the secondary goals looked at the effect on acombination of death from heart disease, heart attacks, or needfor an urgent artery clearing procedure.
Another secondary goal combined deaths from heart disease, heart attacks, hospitalizations for unstable angina or need for any artery clearing procedure.
"These are all things that are very important for patients,"White explained.
When isolated from the composite goals, darapladib didnumerically better at delaying heart attacks. There were 361heart attacks in the drug group and 405 in the placebo group,although the difference missed statistical significance. Therewere also fewer deaths among darapladib patients.
The stroke numbers by comparison were nearly identical - 154versus 152 for placebo.
Darapladib blocks an enzyme known as Lp-PLA2, high levels ofwhich are considered a risk factor for heart disease.
It is believed the drug changes the composition of plaque onartery walls, making it less likely to rupture and cause clogsand serious heart problems.
One sub group of darapladib patients that fared better thanthe overall population was smokers, who had a greater decreasein major adverse events than non-smokers. Previous studies haveshown that smokers have higher Lp-PLA2 levels, so may be moreresponsive to Lp-PLA2 inhibition.
The most common side effects with darapladib were diarrhea,and unpleasant odor in feces, urine and skin.
There was a higher rate of kidney failure reported inpatients who took the Glaxo drug, but White said mostresearchers did not believe that was related to darapladib.
White said he was disappointed the drug failed to meet themain goal of the study. "But there is a message here thatsomething is going on. I wouldn't for one moment think thatthere's nothing going on here and it should be abandoned," hesaid.
Glaxo is pinning its hopes on the study in sicker patientsthat should have results available in two or three months.
"If in the second study you see effects on thecardiovascular end points, this is still a potentially usefuldrug for patients with heart disease," Murray Stewart, Glaxo'shead of Metabolic Pathways Cardiovascular Therapy Area, said ina telephone interview.
"The main thing will be the next study." (Reporting by Bill Berkrot; Editing by Sophie Hares andMeredith Mazzilli)
