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Regulatory News | 05 November 2014 | By Alexander Gaffney, RAC
A new report published by the Tufts Center for the Study of Drug Development (CSDD) validates longstanding data indicating that drugs intended to treat disorders of Central Nervous System (CNS) take longer to develop and are rejected by US Food and Drug Administration (FDA) regulators at a higher rate than are other drugs.
Disorders of the central nervous system are as diverse as they are challenging to treat. Some of the most common CNS disorders include depression, psychosis, epilepsy and Alzheimer's disease. As Tufts’ report notes, these disease are unusually challenging to develop drugs for because they are typically chronic conditions, have complex pathologies and are challenging to objectively measure.
For example, some nervous system disorders, such as Alzheimers' disease, are poorly understood and may have several underlying causes. Even for relatively common disorders such as depression, companies may have a poor understanding of how their drugs—however effective—actually work against a condition. And without a thorough understanding of a disease's pathology, determining if a drug actually worked in a clinical trial can be difficult.
Drugs for these conditions are also associated with unique concerns. For example, in August 2012 FDA released a draft guidance document outlining recommendations that developers of CNS drugs study the potential for their drugs to cause suicidal ideation and behavior in patients.While concerns about links between CNS drugs and suicidal thoughts and actions have long been known, additional clinical requirements for these drugs can also lengthen the amount of time a drug spends in its development phase prior to obtaining FDA approval.
Tufts' report all but confirms what most regulatory professionals working in the CNS space have long known: Developing these drugs is a long and challenging process.
For starters, the drugs have a lower clinical success rate than all other compounds. Just 6.2% of CNS compounds that entered Phase I testing were eventually approved by FDA compared to 13.3% of all other drugs during the 1995-2007 period.
CNS drugs had lower rates of success during every single phase of the clinical development process, with marked differences in Phase II and Phase III testing. "The Phase II-III transition rate was 10 percentage points lower for CNS vs. all other compounds, while the Phase III to NDA/BLA submission rate was 18 percentage points lower," Tufts found.
While CNS approval rates did rise for several years—it peaked at around 11% between 1998 and 2004—it has since declined to an approval rate of around 4-5% on average.
Failure rates weren't the only setback for CNS drugs, however. They needed to wait 19.3 months, on average, for an approval decision over the 1999-2013 period compared to just 14.7 months for all other drugs. This discrepancy has narrowed considerably since 2009, however, and it now takes CNS drugs just 0.8 months longer on average to obtain approval.
In all, the total clinical development time for CNS drugs was 78.1 months during the 2009-2013 period—slightly more than the average for non-CNS drugs.
The study largely comports with existing data on FDA's approval of CNS drugs, including another 2012 report put out by Tufts on the same subject and a 2012 report by the California Healthcare Institute (CHI) and the Boston Consulting Group (BCG).
An April 2013 report by the Manhattan Institute, also authored Tufts experts, had found FDA's neurology review division (Division of Neurology Products) to be among its slowest reviewers of medications, taking 635 days on average to review drugs and taking 1.73 review cycles on average to reach an approval decision. The division was also the worst at meeting Prescription Drug User Fee Act deadlines. However FDA has defended the division, saying the products it reviews are inherently more complex than products approved by other divisions of the Center for Drug Evaluation and Research (CDER).
Tags: CNS, Central Nervous System, CNS Approvals, Tufts CSDD, Report, CNS Drug Mean Approval Times