Report spotlights trial-termination trends	January 2009

By Michael Christel

Termination of clinical trials, most common at Phase II, is a natural consequence of drug development. The huge costs and increased resource demands of late-stage clinical trials are always major considerations, but what truly motivates pharmaceutical companies when making go/no-go decisions is sometimes unclear. Citeline expert tackled the subject in a recent report in which they analyzed terminated Phase II trials in oncology to assess the reasons and strategies behind those tough decisions. 

In its report, “Calling timeout on oncology trials,” Citeline notes that the motivations to stop or go contrast greatly when comparing studies involving a novel drug candidate versus a marketed therapy seeking a new indication or label expansion. Citeline authors ­– who paid specific attention to trials involving solid tumors – found that terminations due to internal drug safety shifts or pipeline reprioritization are cited much more frequently for trials involving novel compounds compared to already commercialized therapies. Surprisingly, however, trials halted due to lagging patient enrollment are four times more likely to involve a marketed drug than a novel compound, Citeline says.

 “It’s a reasonable assumption that patient enrollment for a trial involving a marketed therapy may be better than one for a novel therapy, as there is a greater level of patient comfort in trying a marketed drug for a new disease versus trying an unapproved drug,” says Citeline’s Tracy DeGregorio, who co-authored the report with Christine Blazynski.  “But, in fact, we saw the opposite in terminated Phase II solid tumor trials, indicating that companies may be quicker to pull the plug on a poorly enrolling trial of a marketed drug, as it isn’t dependent upon the trial for time to market.”

 Citeline’s report focused solely on a data set of 367 industry-sponsored oncology trials that were halted in Phase II. According to Citeline, 54% of the terminated trials were testing novel candidates. Nearly 90% of the halted studies were sponsored by a single company.

Citeline experts say questions over efficacy was by far the most frequently cited reason for trial termination in their dataset. They note that the number of trials involving novel candidates only slightly exceeds that for trials exploring expanded labeling.

“Despite a company’s lifecycle strategy, it needs to adjust quickly to results,” the report states. “The data suggests that companies show little hesitation in terminating Phase II trials when efficacy is in doubt.”

High Phase II attrition is particularly evident when examining trial terminations by company, an indication that some are making their decisions sooner than others. Among those companies reporting two or more discontinued oncology programs, most notably, according to Citeline, are Sanofi-Aventis, Roche, and UCB, all of which had no cancer drugs terminated after Phase II. Meanwhile, Citeline says, GlaxoSmithKline had 87% of their terminations occurring at or before Phase II, followed  by Novartis at 75%, Genzyme at 67%, and Pfizer at 65%.