Post-Approval Exploratory Trials with Pregabalin Often Fail Save

A systematic review of 238 pregabalin (Lyrica) trials for nonapproved indications shows that nearly two-thirds yielded uncertain evidence of efficacy, thereby questioning the off-label use or endorsement in clinical practice guidelines.

Pregabalin was FDA approved in 2004 for neuropathic pain and in 2007 for fibromyalgia.  In October 2017 the FDA approved Lyrica CR (an extended-release pregabalin for neuropathic pain conditions). Pregabalin is expected to go off patent in December 2018 and it's sales are expected to drop from $5 billion in 2018 to roughly $3 billion in 2019.

This review set out to establish the findings of post-approval exploratory and confirmatory postapproval trials (often done in off-label indications) with pregabalin. 

They found 238 trials assessing the efficacy of pregabalin in 33 indications; 5  of whom later received European Medicines Agency and/or US FDA marketing approval.

For new indications 67% (22 of 33), trials failed to generate positive proof of efficacy and generally these were not changed over time or by repeat studies.

These findings question the practice of (often smaller) exploratory and confirmatory trials on new or off-label indications.  Stronger oversight by regulatory agencies and manufacturers should be encouraged to avoid the risk of inappropriate promotion and use of newly approve drugs.