Identifying and Neutralizing the Cause of Deadly Side Effects of Eli Lilly & Co. Anticancer Drug ALIMTA

The Problem

Eli Lilly & Company, the pharmaceutical firm, sought to develop and bring to market a promising new “antifolate” class of cancer drug, ALIMTA. During clinical trials, the drug showed remarkable effectiveness in combating tumors in a particular form of lung cancer. But unpredictable, life-threatening and, in a few cases, fatal side effects suffered by patients using the drug threatened its future. $300 million had already been invested, but the severity of the drug’s side effects forced the suspension of ALIMTA’s development.

The Analytics Solution

In an effort to understand the sources of the toxic side effects, researchers collected data on certain “markers” (like elevated levels of “total plasma homocysteine” (tHcl), indicating a folic acid deficiency) indicating deficient levels of certain vitamins, from 246 patients using the drug. Multivariate methods were applied to identify markers that might predict a severe toxic reaction to ALIMTA. Using the markers in a multiple logistic regression model made it possible to quantify the risk of developing toxicities and to generate ideas about how to improve ALIMTA’s safety. The analysis determined that folic acid and vitamin B12 deficiencies were associated with the most severe toxicities. Subsequent medical experiments determined that giving patients supplements of these vitamins enabled patients to avoid the potentially deadly side effects.

The Value

Identifying the toxic side effects through analytics-based techniques made it possible for ALIMTA to gain approval from regulators in Europe and the U.S. The drug was initially approved for use in treating a rare form of lung cancer (mesothelioma) and later was approved for treating more common forms of lung cancer after initial chemotherapy. In addition, ALIMTA is being studied as a treatment for other common cancers such as breast, colorectal, head and neck. The number of lives that will be saved as a result of this drug’s general availability has not been calculated but is assumed to be large.