Oncology NEWS International. Vol. 16 No. 8 August 1, 2007
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`Oncology NEWS International. Vol. 16 No. 8
`Cancer Care & Economics
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`Phase III failure rates in oncology drugs
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`unacceptable
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`By Ramaswamy Govindan, MD | August 1, 2007
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`These are exciting times in oncology. Over the past 2 decades, we have made remarkable progress in our
`understanding of the molecular and cellular processes involved in cancer progression. Along the way,
`we've seen some profound advances in the diagnosis and treatment of cancer. Nonetheless, the
`development of new cancer drugs is largely an inefficient and costly process, which has resulted in
`depressing approval rates and a pipeline clogged with failed compounds and billions of wasted dollars.
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`Although success rates vary considerably within the pharmaceutical industry, oncology drugs have the
`highest failure rates among the various therapeutic areas. For instance, about 20% of cardiology drugs
`succeed, whereas only about 5% of new oncology compounds go from first—in—human trial to FDA
`approval. In non-small-cell lung cancer alone, between 1990 and 2005, a total of l,63l new drugs were
`studied in phase II. Only seven of these new agents gained FDA approval.
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`For balance, it's worth noting that oncology drugs are attacking disease entities of enormous complexity,
`and FDA standards for approvalwith good reasonare increasingly more demanding. That said, the high
`attrition rate in drug development becomes more alarming when we realize that the cost of discovering
`and developing a new drug can be as much as $900 million.
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`Moreover, the vast majority of failure occurs late in the pipeline, in phase II and III. A failure at phase
`III is particularly painful, We lose not only the hope of a promising new compound but also precious
`capital expenditure. This failure rate is unacceptable, and we are part of the problem, not part of the
`solution.
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`We have learned that using response rate alone in sinall—sample phase II trials is not terribly meaningful.
`Then we jump to phase III studies based on historic controls that we know can be terribly misleading. A
`better endpoint in phase II studies would be progression—free survival even with all its limitations. But
`more important, we're currently accepting a 30% rate of improvement in a phase II randomized trial as
`justification to move to phase III.
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`Drug development is a high-stakes game; modest results are simply not good enough30% improvement
`in phase II doesn't translate into 30% improvement in phase III. It translates into an unacceptably high
`rate of failure.
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`We must make a concerted effort to set the bar higher and design trials for success, not failure. We need
`to abandon the current oncology paradigms for phase I and II clinical trials and adopt a principle that
`requires larger trials with bettervalidated preclinical targets. Raising our standards in early trials will
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`http: //www. cancernetwork .com/display/article,’1C165/E-C633
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`1
`OSI EXHIBIT 2008
`APOTEX V. OSI
`IPRZO16-01284
`
`OSI EXHIBIT 2008
`APOTEX V. OSI
`IPR2016-01284