Expecting to improve its odds of success for the experimental heart drug darapladib, a top drug prospect that failed its first late-stage test, investigators at GlaxoSmithKline ($GSK) have changed up the primary endpoint in the remaining Phase III study that reads out later this quarter.
In its Q1 RD review out today, GSK noted that the new primary endpoint in its SOLID study is the drug’s effect on the number of coronary events suffered by patients, substituting for the original: time to the occurrence of the first major cardiac event for patients suffering from chronic coronary disease. Coronary events originally was listed as a secondary endpoint.
The executive steering committee overseeing SOLID made its decision after the first Phase III trial demonstrated fairly clearly that the drug did not have much of an impact in thwarting strokes, a factor that led to its failure for the cardiac events endpoint. But investigators got what they felt was a clear signal that the drug could be working on the coronary event hurdle, which adds a separate signal and drops stroke from the list.
“In the STABILITY study darapladib had clearly no impact on stroke at all,” Liz Tarka, the physician project leader on the SOLID trial, tells FierceBiotech. So the team concluded that “stroke wouldn’t be a factor and shouldn’t be measured.”
There’s a lot riding on the results this quarter. Darapladib was one of the key reasons why GSK decided to buy out Human Genome Sciences, offering a CVR for the drug that has fallen dramatically in value. Investigators, though, have been sounding optimistic about its chances in the second study, which could open the door to an approval.
But it’s no sure thing.
STABILITY tracked a narrow benefit in the rate of major coronary events–9.3% in the darapladib group over 3.7 years and 10.3% for the placebo arm. The p value was 0.045, indicating “nominal” significance. Similar effects were observed for the composite of total coronary events, which occurred in 14.9% of patients on darapladib versus 16.1% on placebo, GSK noted earlier.
“I’m convinced there is a signal here of efficacy,” Harvey White, who co-chaired the first study, told Reuters at a meeting of the American College of Cardiology.
Tarka adds that the company alerted all the regulatory groups affected by the changeup in the U.S., Europe and Japan.
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