UK’s CMR reported that success rates in Phase II clinical trials which are already lower than at other stages of drug development, are getting markedly worse. The failure rate(or success-depending on whether you like to see the glass half full or half empty) is currently cited as around 50%.

They reviewed drug development projects undertaken by 16 companies which represent 60% of global R&amp spending.

They found that Phase II success rates for new development projects had fallen from 28% in 2006–2007 to 18% in 2008–2009, although these rates did vary between therapeutic categories as well as between small molecules and biologics.

2008-2010 failures

Of the 108 reported Phase II failures for new drugs and major new indications of existing drugs, reasons for failure were reported for 87 of the projects.

-51% (44 out of 87) were due to insufficient efficacy
-29% (25) for strategic reasons
-19% (17) for preclinical safety reasons.

Of the 25 projects terminated for strategic reasons, 16 involved validated targets such as peroxisome proliferator activated receptor-ã (PPARã) or factor Xa, thus “suggesting that some of these failures were due to inadequate differentiation from more advanced drugs in the same class or from drugs with similar indications in another mechanistic class.

Of the 21 failures for which no reasons were reported, 17 involved validated targets, “although not always in an approved indication for drugs affecting that target”.

They concluded 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 the change in the benefit–risk balance of a known target in a new patient population.”

Therapeutic areas

68% (73 out of 108) failures were in four therapeutic areas:

-alimentary/metabolism (23 failures, of which 14,(61%) were for diabetes)
-cancer (21)
-neuroscience (17) and
-cardiovascular (12).

...”the finding that a substantial proportion of Phase II failures were due to strategic reasons suggests that one important underlying factor could be overlapping R&amp activity between companies with drugs in Phase II trials,” Arrowsmith suggests.

“This raises the question of whether an increase in collaborative efforts between companies up to the point of proof-of-concept for novel targets or mechanisms might be more cost-and time-effective.”

Standard of care (SOC)

Industry commentator Derek Lowe's (Pipeline blog for Corante) guess is that compounds “seem to have been targeting areas where there was already competition, and they didn’t differentiate themselves enough from the SOC to be worth continuing”.

The relatively high failure rates in neuroscience and oncology are in keeping with the traditional sharp degree of risk associated with these categories while diabetes is “a tough field – big market, but pretty well-served, making efficacy versus the standard of care a high bar to clear, and this while the FDA’s safety requirements have gotten very stiff indeed”.

Cardiovascular disease, though, has traditionally enjoyed one of the better success rates in clinical trials, Lowe notes.

“Perhaps that one is also suffering from the SOC being pretty good (and often generic, or soon to be),” he comments. “So the high-success-rate mechanisms of the old days are well covered, leaving you to try your luck in the riskier ideas, while still trying to beat some pretty good (and pretty cheap) drugs.”

Sources: Nature / Pharma Clinical Alerts / CMR -Thomson Reuters