If numbers tell a story, then the numbers pertaining to Phase II clinical trials offer a sobering tale. A new analysis finds that Phase II success rates fell from 28 percent in 2006 and 2007 to just 18 percent in 2008 and 2009, according to the Centre for Medicines Research, which examined trials undertaken by 16 drugmakers.
The upshot? Phase II success rates are lower than at any other phase of development, although success rates do vary between therapeutic areas and between small molecules and biologics. Nonetheless, the implication is that the overall attrition of late-stage drug development seems to be unsustainably high. The findings appear in Nature Reviews Drug Discovery.
Specifically, the analysis looked at 108 reported Phase II failures from 2008 to 2010 for new drugs and major new indications of existing drugs. Of these, 87 reported the reasons for failure. The breakdown? Well, 51 percent, or 44 of 87, were due to insufficient efficacy; 29 percent, or 25 of 87, were due to strategic reasons and 19 percent, or 17 of 87, were due to clinical or preclinical safety.
Of the 25 failures, 16 involved validated targets, suggesting some failures can be blamed on inadequate differentiation from more advanced drugs in the same class or from drugs with similar indications in another mechanistic class, the journal writes. Of 21 failures for which reasons were not reported, 17 involved validated targets, although not always in an approved indication for drugs affecting that target.
Meanwhile, 68 percent, or 73 of 108 failures fell into four therapeutic areas: alimentary/metabolism, cancer, cardiovascular, and neuroscience. And 61 percent, or 14 of 23 failures in alimentary/metabolism, were for diabetes.
“Strategic failures result from too many companies chasing the same targets or because the drug was a long shot (and) wishful thinking,” study author John Arrowsmith, scientific director at Thomson Reuters, which owns CMR, tells Outsourcing Pharma. "It would seem reasonable to conclude that some of these failures were due to insufficient evidence of an efficacy advantage over a more advanced drug.
“However, it is important not to rule out that failure could be due to a change in the benefit-risk balance of a known target in a new patient population” he added. “The increased losses from Phase II have probably been catalysed by recent M&A activity and the need to manage R&D costs.” The increase in focus on rare disease and patient stratification will open up the opportunity space but as change is driven by the emerging science then the problem will not go away completely...There will also be an increase in consortia and partnering so this should also temper the strategic failures.
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