Opinion

The Great Debate

Alzheimer’s setback shows difficulty of drug development

September 23, 2010

DUTCH-FLOWERS/

By Peter Pitts
The opinions expressed are his own.

Pharmaceutical firm Eli Lilly recently announced that it would halt clinical tests for an experimental Alzheimer treatment. The drug’s failure was extremely disappointing, as it represented one of only five Alzheimer’s drugs under development to have even reached late-stage clinical trials.

Lilly’s announcement exemplifies the long odds that most drug researchers face in trying to identify cures for the world’s most debilitating diseases.

What needs to be addressed are the twin issues of drug development and regulatory science. Both are lagging.

Too many drug trials — almost 50 percent — are failing in the Phase III trial stage, the latest one because they are mired in regulatory treacle. This is an unsustainable economic model from an R&D standpoint, and the impact of Alzheimer’s on patients, their families, and American healthcare is devastating.

Better, more current and predictable scientific research and standards must be developed and devoted to streamlining the critical path. Investment in basic research is not enough. Specifically, new development tools, such as biomarkers, microarrays and other diagnostic tools, are needed to improve the predictability of the drug-development cycle and to lower the cost of research by helping industry identify product failures earlier in the clinical trials process.

A quarter-century ago, the success rate for a new drug used was about 14 percent. Today, a new medicinal compound entering Phase 1 testing — often after more than a decade of preclinical screening and evaluation — is estimated to have only an 8 percent chance of reaching the market. For very innovative and unproven technologies, the probability of a product’s ability to make it to the market is even lower. We must work together to turn that around.

When Thomas Edison was asked why he was so successful, he responded, “Because I fail so much faster than everyone else.” Consider the implications if the FDA could help companies fail faster. Using the lower end of the Tufts University estimate of the average pre-tax cost of new drug development, $802 million:

  • A 10 percent improvement in predicting failure before clinical trials could save $100 million in development costs.
  • Shifting 5 percent of clinical failures to Phase 1, the earliest stage, from Phase 3, the latest stage, reduces out of pocket costs for developers by $15-$20 million.
  • Shifting of failures to Phase 1 from Phase 2, the middle stage, would reduce their out of pocket costs by $12-$21 million.

All of these dollars could then be reinvested in other innovative development programs for new life-saving medicines.

For all that modern science has to offer, developing new treatments is still very much an art, in which hunches, intuition, and luck play a critical role. The odds are long. But for more medicine that is affordable and innovative, we need up-to-date regulations that compliment the drug trial process in order to take these chances, which is precisely the mission of the FDA’s moribund Reagan-Udall Foundation. The failure of Congress to free-up the seed funding the foundation has called for in the 2007 FDA Amendments Act must be corrected.

Senator Ted Kennedy said the Reagan-Udall Foundation “will make new research tools and techniques available to the entire research community, shortening the time it takes to develop new drugs and reducing costs for patients.”

Shortly before his death, I had the privilege of a private meeting with Nobel Laureate Joshua Lederberg. The topic of conversation was the future of the FDA and the agency’s Critical Path initiative. We talked about the state of applied research, the prioritization of development science, biomarkers, and a host of other future-oriented issues. He talked. I took a lot of notes.

At the end of the meeting, he put everything into perspective in a single sentence. He leaned over the table and said, “The real question should be, is innovation feasible?”

Yes, it is. And the FDA should allow it to happen.

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