By Learning From Failures, Lilly Keeps Drug Pipeline Full explains how Lilly explores every failure, because even “failed” drugs can be turned into successes:
Lilly has long had a culture that looks at failure as an inevitable part of discovery and encourages scientists to take risks. If a new drug doesn’t work out for its intended use, Lilly scientists are taught to look for new uses for a drug. In the early 1990s, W. Leigh Thompson, Lilly’s chief scientific officer, initiated ‘failure parties’ to commemorate excellent scientific work, done efficiently, that nevertheless resulted in failure.
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Other drug companies are also seeing the importance of tolerating — and learning from — failure, a valuable strategy since about 90% of experimental drugs in the industry fail. For example, Pfizer Inc. originally developed the blockbuster impotence drug Viagra to treat angina, or severe heart pain.
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Many Lilly drugs have risen from failure. Evista, now a $1 billion-a-year drug for osteoporosis, was a failed contraceptive. Strattera, a hot-selling drug for attention deficit/hyperactivity disorder, bombed out as an antidepressant. A promising cardiovascular drug called a PPAR-alpha-agonist, which lowers fat levels in the blood, arose from a failed asthma project. The antidepressant Cymbalta, for which Wall Street has high hopes, failed in its original trials until a Lilly scientist upped the dosage.
Dr. Nyikiza, the Rwandan mathematician, is one of Lilly’s “failure” experts. He helped to save Alimta, an experimental chemotherapy drug, and to turn it into a successful treatment for mesothelioma (a rare cancer caused by asbestos):
The story of Alimta’s salvation begins in 1992 with an out-and-out failure: a new drug called lomotrexol that made patients ill in its trials. For the post-mortem analysis, Lilly tapped Dr. Nyikiza, the Rwandan mathematician, who specialized in the failure analysis of complex systems — a branch of math called stochastic processes.Dr. Nyikiza, who grew up on a peanut and banana farm, developed this interest on boyhood hunting trips in Rwanda and neighboring Tanzania. From his grandfather, he learned all about the myriad factors that lead to a successful hunt or a disastrous one. Among them were wind speed and direction, grass conditions and the presence of predators. “Don’t hunt a lone antelope,” his grandfather cautioned, because lone antelopes tend to attract lone lions.
Dr. Nyikiza ended up in a gifted program at a Rwandan high school run by Jesuit missionaries. After getting a bachelor’s degree in statistics and applied economics in Rwanda, Dr. Nyikiza worked on a project funded by the U.S. Agency for International Development, doing population analysis for the government of Rwanda. Then the U.S. agency and the Rwandan government sent him to Indiana University where he got a doctorate in mathematics.
Before joining the drug industry, Dr. Nyikiza analyzed failures in everything from aircraft engines to truck transmissions. In a job for the Swiss National Science Foundation, he looked at what makes certain paper money prone to counterfeiting.
In 1990, a research executive from Syntex Corp., since acquired by Roche Holding AG, sat next to him on a flight from Zurich to Chicago and concluded Dr. Nyikiza’s expertise would be useful in an industry where almost everything fails. He moved to Lilly from Syntex in 1993.
At the time, Lilly was trying to learn from the failure of lomotrexol. Like Alimta, lomotrexol had induced neutropenia, a white-blood-cell disease causing immune deficiency, severe diarrhea and sometimes death. Lilly asked Dr. Nyikiza to find out why the drug failed. He and three colleagues spent most of a year on the effort, analyzing blood samples and traveling to question world experts. They settled on 64 blood markers that might predict which patients would be afflicted by the devastating side effect. Finally, one called homocysteine emerged. Every patient sickened by lomotrexol had high levels of homocysteine, a common amino acid.
Homocysteine is produced when human cells lack the vitamin folic acid. The conclusion from Dr. Nyikiza’s team — that the patients who died had a deficiency in folic acid — would become crucial during the crisis in the Alimta mesothelioma study.
In short, giving Alimta patients folic acid reduced the dangerous side effects without reducing the drug’s effectiveness.