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WASHINGTON (Reuters) - A new type of heart drug being developed by GlaxoSmithKline, which failed the main goal of a Phase III study of patients with chronic but well-treated heart disease, showed signs of potential benefit, the trial's co-leader said.
The results presented at the American College of Cardiology scientific meeting in Washington on Sunday provided a glimmer of hope that the medicine, darapladib, may have value.
"I'm convinced there is a signal here of efficacy and the drug 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 the medicine within 30 days of a heart attack.
A positive result in that study could put the drug back on track, after it was largely discounted by analysts and investors following the first Phase III failure.
The stakes are high for the British drugmaker as gaining full 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 sales potential of darapladib.
Glaxo had previously said darapladib did no better than a placebo in decreasing the risk of a combination of cardiovascular death, heart attack and stroke in the trial called Stability.
The trial involved 15,828 patients followed for a median of 3.7 years.
For those taking the Glaxo pill, 9.7 percent had one of the major adverse events compared with 10.4 percent for the placebo, which was not a statistically significant difference.
A lack of any impact on stroke prevention appears to have contributed to the failure of the study, researchers surmised.
In addition, the effect of the Glaxo drug may have been muted by the high level of care the patients were receiving.
Almost all were taking statins and aspirin and nearly 80 percent were on blood pressure drugs - all known to decrease the risk of heart attacks, strokes and death.
"We're setting a very high bar and we may have affected our ability to (determine) a treatment effect," said White, director of the coronary care unit at Auckland City Hospital in New Zealand.
The drug's impact on the secondary goals of the study was deemed "nominally significant" by researchers, meaning they saw the potential of a clinically meaningful effect despite falling short of statistical significance.
One of the secondary goals looked at the combined number of people who died from heart disease, had a heart attack, or needed urgent artery clearing procedures.
The other secondary goal studied the combined number of people who died from heart disease, had a heart attack, were hospitalized for unstable angina or required any artery clearing procedure.
"These are all things that are very important for patients," White explained.
When isolated from the composite goals, darapladib did numerically better at delaying heart attacks.
There were 361 heart attacks in the drug group and 405 in the placebo group, although the percentage difference missed statistical significance. There were also fewer deaths among darapladib patients.
The stroke numbers by comparison were nearly identical - 154 versus 152 for placebo.
Darapladib blocks an enzyme known as Lp-PLA2, high levels of which are considered a risk factor for heart disease.
It is believed the drug changes the composition of plaque on artery walls, making it less likely to rupture and cause clogs and serious heart problems.
One sub group of darapladib patients that fared better than the overall population was smokers, who had a greater decrease in major adverse events than non-smokers.
"Previous studies showed that smokers have higher Lp-PLA2 levels, and it's plausible that smokers may be more responsive to Lp-PLA2 inhibition," White said.
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 in patients who took the Glaxo drug, but White said most researchers did not believe that was related to darapladib.
White said he was disappointed the drug failed to meet the main goal of the study, the results of which were also published in the New England Journal of Medicine.
"But there is a message here that something is going on. I wouldn't for one moment think that there's nothing going on here and it should be abandoned," he said.
Glaxo, meanwhile, is pinning its hopes on the next large study in sicker patients that should have results available in two or three months.
"If in the second study you see effects on the cardiovascular end points, this is still a potentially useful drug for patients with heart disease," Murray Stewart, Glaxo's head of Metabolic Pathways Cardiovascular Therapy Area, said in a telephone interview.
"The main thing will be the next study."
Reporting by Bill Berkrot; Editing by Sophie Hares