N E W S & A N A LY S I S
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`BIOBUSINESS BRIEFS
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` T R I A L WAT C H
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`Phase II failures: 2008–2010
`
`Well-conducted Phase II clinical trials provide
`the data required to determine whether
`there is a case to be made, both scientifically
`and commercially, for progressing a drug
`candidate into Phase III trials. At present,
`however, Phase II success rates are lower than
`at any other phase of development. Analysis
`by the Centre for Medicines Research (CMR)
`of projects from a group of 16 companies
`(representing approximately 60% of global
`R&D spending) in the CMR International
`Global R&D database reveals that the Phase
`II success rates for new development projects
`have fallen from 28% (2006–2007) to 18%
`(2008–2009), although these success rates do
`vary between therapeutic areas and between
`small molecules and biologics. As the current
`likelihood of a drug successfully progressing
`through Phase III to launch is 50% (Nature Rev.
`Drug Discov. 10, 87; 2011), the overall attrition
`of late-stage drug development seems to be
`unsustainably high.
`To help understand these trends, Thomson
`Reuters Life Science Consulting analysed the
`108 reported Phase II failures from 2008 to 2010
`for new drugs and major new indications of
`existing drugs (Drug News Perspect. 22, 39–51;
`2009; Drug News Perspect. 23, 48–63; 2010;
`Drugs Today, 47, 27–51; 2011). Out of these, 87
`reported the reasons for failure (FIG. 1a): 51%
`(44 out of 87) were due to insufficient efficacy,
`29% (25 out of 87) were due to strategic reasons
`and 19% (17 out of 87) were due to clinical or
`preclinical safety reasons. Out of the 25 failures
`that were terminated for strategic reasons, 16
`involved validated targets such as peroxisome
`proliferator activated receptor-γ (PPARγ) and
`factor Xa, therefore 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.
`Out of the 21 failures for which reasons were
`not reported, 17 involved validated targets,
`although not always in an approved indication
`for drugs affecting that target. Again, 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 the change in the
`benefit–risk balance of a known target in a
`new patient population. These data also show
`that 68% (73 out of 108) of failures fell into
`four therapeutic areas (FIG. 1b): alimentary/
`metabolism, cancer, cardiovascular, and
`neuroscience. Notably, 61% (14 out of 23)
`of failures in alimentary/metabolism are for
`diabetes.
`Although it is difficult to draw conclusions
`from these data, 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&D
`activity between companies with drugs
`in Phase II trials. 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.
`
`John Arrowsmith is a Scientific Director at Thomson
`Reuters, 77 Hatton Garden, London EC1N 8JS, UK.
`e-mail: john.arrowsmith@thomsonreuters.com
`
`The author declares no competing financial interests.
`
`a
`
`Efficacy
`
`Pharmacokinetics
`1%
`/bioavailability
`
`Strategic
`
`b
`
`51%
`
`29%
`
`19%
`
`11%
`
`16%
`
`20%
`
`32%
`
`21%
`
`Other (35)
`Alimentary/
`metabolism (23)
`Cancer (21)
`Neuroscience (17)
`Cardiovascular (12)
`
`Safety
`Figure 1 | Phase II failures: 2008–2010. The 108 failures are divided according to reason for failure
`Nature Reviews | Drug Discovery
`when reported (87 drugs) (a) and therapeutic area (b).
`
`NATURE REVIEWS | DRUG DISCOVERY
`
` VOLUME 10 | MAY 2011 | 1
`
`© 2011 Macmillan Publishers Limited. All rights reserved
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