Sunday, March 30, 2014

UPDATE 1-Glaxo heart drug that failed trial shows potential benefit

Sun Mar 30, 2014 11:32am EDT





<span id="articleText"/> (Adds study details, researcher, Glaxo comment, background)



<span id="midArticle_0"/> By <a href="http://ift.tt/1rA2N0L;Bill Berkrot and Ransdell Pierson



<span id="midArticle_1"/> WASHINGTON, March 30 (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.



<span id="midArticle_2"/> 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.



<span id="midArticle_3"/> "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.



<span id="midArticle_4"/> 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.



<span id="midArticle_5"/> 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.



<span id="midArticle_6"/> 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.



<span id="midArticle_7"/> Human Genome had rejected an earlier $2.6 billion offer, claiming that Glaxo was underestimating the blockbuster sales potential of darapladib.



<span id="midArticle_8"/> 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.



<span id="midArticle_9"/> The trial involved 15,828 patients followed for a median of 3.7 years.



<span id="midArticle_10"/> 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.



<span id="midArticle_11"/> A lack of any impact on stroke prevention appears to have contributed to the failure of the study, researchers surmised.



<span id="midArticle_12"/> In addition, the effect of the Glaxo drug may have been muted by the high level of care the patients were receiving.



<span id="midArticle_13"/> 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.



<span id="midArticle_14"/> "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.



<span id="midArticle_15"/><span id="midArticle_0"/> SECONDARY GOALS IMPORTANT



<span id="midArticle_1"/> 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.



<span id="midArticle_2"/> 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.



<span id="midArticle_3"/> 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.



<span id="midArticle_4"/> "These are all things that are very important for patients," White explained.



<span id="midArticle_5"/> When isolated from the composite goals, darapladib did numerically better at delaying heart attacks.



<span id="midArticle_6"/> 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.



<span id="midArticle_7"/> The stroke numbers by comparison were nearly identical - 154 versus 152 for placebo.



<span id="midArticle_8"/> Darapladib blocks an enzyme known as Lp-PLA2, high levels of which are considered a risk factor for heart disease.



<span id="midArticle_9"/> 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.



<span id="midArticle_10"/> 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.



<span id="midArticle_11"/> "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.



<span id="midArticle_12"/> The most common side effects with darapladib were diarrhea, and unpleasant odor in feces, urine and skin.



<span id="midArticle_13"/> 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.



<span id="midArticle_14"/> 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.



<span id="midArticle_15"/> "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.



<span id="midArticle_0"/> Glaxo, meanwhile, is pinning its hopes on the next large study in sicker patients that should have results available in two or three months.



<span id="midArticle_1"/> "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.



<span id="midArticle_2"/> "The main thing will be the next study." (Reporting by Bill Berkrot; Editing by Sophie Hares)



<span id="midArticle_3"/>

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