Developing drugs to treat a wide array of central nervous systems disorders—including depression, psychosis, epilepsy and Alzheimer’s disease—takes longer and has an overall success rate of less than half that of other types of drug candidates.
Those are the key findings of a new study by Tufts University’s Center for the Study of Drug Development. To understand the challenges of CNS drugs, Tufts researchers examined the development and approval histories of 274 CNS and 1,168 non-CNS investigational compounds tested in humans between 1995 and 2007. During this period, only 6.2 % of CNS drugs attained clinical approval, less than half of the 13.3% rate for the other compounds.
CSDD also examined the development and approval phases of 42 CNS and 345 non-CNS therapeutic compounds that gained regulatory approval between 1999 and 2013. During this period, the average clinical development time for marketing approval was 12.8 months, or 18% longer than for non-CNS compounds. A closer look revealed only one in six CNS compounds received a priority review rating from the FDA, compared to nearly half of all non-CNS compounds.
“CNS drugs are more challenging to develop than other medicines because the conditions they aim to treat typically are chronic and complex, and clinical endpoints often are difficult to measure,” Joseph A. DiMasi, director of economic analysis at Tufts CSDD and author of the study, said in a statement. “That’s why CNS drug development takes longer and has a lower likelihood of overall clinical success than non-CNS drug development.”
The findings, reported in the November/December CSDD Impact Report, showed:
• From 1999 to 2013, the average approval time for each clinical phase for CNS compounds approved for marketing in the U.S was 19.3 months, 31% longer than the 14.7 months for non-CNS approvals
• Despite lengthier approvals for both clinical phases and marketing, and lower clinical success rates, CNS approvals have held steady, accounting for one in 10 approvals since the 1980s
• By contrast, the share for new approvals of cardiovascular compounds declined from 27% of approvals in the 1980s to 13% for the 2010-2013 period, while anti-infective approvals plunged from 25% to 9 %
• The biggest gains were approvals for cancer compounds, as anti-neoplastic compound approvals soared from 5% in the 1980s to 29% of all approvals in the 2010 -2013 period.
DiMasi’s findings echo a Journal for Clinical Studies report in December 2011 about the innumerable obstacles, both perceived and genuine, in gaining regulatory approval of CNS drugs. That study cited a general bias regarding psychiatric illness and drugs and a number of special concerns with CNS development.
“Many lay people and even healthcare providers still inaccurately view CNS disorders as somehow less important than ‘real’ diseases,” that report stated. “This attitude belittles the value of CNS treatments, which are often seen as disparate from more ‘physical’ ailments.”
That report, written by Worldwide Clinical Trials CEO Neal R. Cutler, M.D., and Henry Riordan, Ph.D., executive vice president, CNS franchise lead, said CNS drugs are viewed as having a relatively high risk and lower priority than drugs in other indications. They pointed to the relatively poor predictive validity of preclinical models and lack of accepted biomarkers and surrogates of many CNS drugs by regulatory authorities and the scientific community.