GlaxoSmithKline's blockbuster dreams dashed as darapladib goes 0-for-2 in PhIII

GlaxoSmithKline's ($GSK) last-minute gambit to switch the primary endpoint in its remaining Phase III study of the heart drug darapladib failed to pay off. The pharma giant says that its top cardio prospect flunked the second big trial just as it had the first, leaving the pharma giant staring at a likely writeoff of a one-time megablockbuster hopeful.

GlaxoSmithKline's corporate headquarters in Brentford, London--Courtesy of GlaxoSmithKline

Investigators working on the two late-stage studies, which enrolled a total of 30,000 patients, were convinced that they saw signs of drug activity in the data from the first study, which tracked the time it took patients to reach the first major cardiac event. With little effect on strokes, one of the key measures on that endpoint, the company opted to switch to major coronary events. But even bypassing strokes failed to move the drug over the goal line on efficacy compared to a placebo.

GlaxoSmithKline did not report the data from this second study, saying it would release results at a later scientific session.

GSK R&D chief Moncef Slaoui

The failure marks a major setback for GlaxoSmithKline and R&D chief Moncef Slaoui, who had been excited by the idea of an Lp-PLA2 drug that promised to reduce arterial plaque in patients. Darapladib was the key reason why GlaxoSmithKline engineered the buyout of Human Genome Sciences.

GlaxoSmithKline has won a slate of new drug approvals over the past 18 months, but generally the company is following well worn R&D paths, adding new and improved medications in fields it understands extremely well, like respiratory diseases. To strike off into uncharted waters along a lonely disease pathway isn't characteristic of the company, which has also experienced high profile failures for a Duchenne muscular dystrophy drug and the cancer vaccine MAGE-A3, now down to its last read out after a series of late-stage flops. Given Glaxo's recent decision to switch out its cancer drug portfolio for Novartis' ($NVS) vaccines group, it's also less likely that we'll see the U.K. pharma giant try developing another drug like this again anytime soon.

Darapladib also provided a cautionary tale on investigators' often unwavering belief in experimental drugs, whatever the data are saying. After the first Phase III failure, lead investigator Harvey White looked over the data and told Reuters, "I'm convinced there is a signal here of efficacy." Touting a clear failure as a veiled success is usually left to small biotechs with little else in the pipeline.

Some analysts once talked about the billions of dollars GlaxoSmithKline could earn with a drug like this, but others--like Bernstein's Tim Anderson--were reluctant to tie a dollar figure to a high-risk project like this.

GlaxoSmithKline, though, isn't quite ready to completely give up yet.

"We will now work to further analyse the data and better understand the findings," says Patrick Vallance, GSK's president of pharmaceuticals R&D.

- here's the release
- here's the story from Reuters

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