CNS Drugs Longer to Develop, Approve: Tufts Center
A Tufts Center for the Study of Drug Development analysis of 509 drugs and biologics approved by FDA from 2000 to 2017 found that central nervous system (CNS) drugs take 20% longer to develop and approve versus non-CNS products. “Due to the complex nature of the conditions they are developed to treat, CNS drugs face greater development challenges compared to non-CNS drugs, due in large part to our poor understanding of the underlying pathophysiology of many of the disorders, as well as difficulty identifying and measuring appropriate clinical endpoints,” the Center says in its September/October Impact Report (purchase or subscription required). “As a result, CNS drugs typically spend more time in clinical development and regulatory review, and they experience lower approval rates, compared to non-CNS drugs. Despite these challenges, CNS drug approvals by FDA as a share of all drug approvals not only has remained relatively steady over nearly four decades, but has increased slightly over that time.”
The center says the situation poses both opportunities and challenges for drug developers. The opportunities, it says, lie in the estimate that CNS disorders will constitute nearly 15% of the global disease burden by 2020, while the challenges are to decrease development time and increase success rates without sacrificing safety and simultaneously reigning in overall development costs.
The researchers report that since the 1980s, CNS share of new drug approvals in the U.S. has remained stable at 10%-12%. The most prevalent disease areas among the 57 CNS drug approvals during 2000-2017 were epilepsy and psychosis, each with 10 drug approvals. From 2000-2008 and 2009-2017, approval shares for multiple sclerosis rose from 0% to 15%, for psychosis from 13% to 21%, and for epilepsy from 17% to 18%.
Four disease areas decreased in prevalence from the first half of the study period to the second half, the report says. The Alzheimer’s share of approvals decreased from 13% to 0%, the Parkinson’s share from 13% to 3%, the sleep disorder share fell from 13% to 6%, and the depression share decreased from 8% to 6%.
Mean clinical development time for CNS approvals was 36% longer (2.3 years) than for non-CNS drugs in 2000-2005, 41% longer (2.6 years) in 2006-2011, but 6% shorter (0.4 years) in 2012-2017. Mean clinical development time for CNS drugs decreased from a high of 8.9 years in 2006-2011 to a low of 6.6 years in 2012-2017, compared to a low of 6.3 years in 2006-2011 and a high of 7.0 years in 2012-2017 for non-CNS drugs.
During 2000-2017, mean approval phase time for CNS drugs was 19.1 months, or 38% longer than for non-CNS drugs. Mean total phase time (sum of clinical and approval phase lengths) for specific CNS diseases during 2000-2017 ranged from 8.2 years for anti-psychotics to 12.6 years for multiple sclerosis, a 54% difference. While multiple sclerosis approvals had the longest clinical development and total phases, they had the lowest average approval phase at 11.4 months, which was 50% lower than the highest average approval phase of 22.6 months for Parkinson’s approvals.
During 2000-2017, Tufts reports, 28.1% of CNS drug approvals received a priority rating from FDA, compared to 51.4% for all non-CNS drugs. And during the same period 22.8% of CNS approvals obtained an orphan drug designation for the original indication approved, compared to 33.1% for non-CNS approvals.