“Repurposed” medications you may know: aspirin in acute heart attacks, to help prevent colorectal cancer and to help prevent clots; diphenhydramine (aka Benadryl) for OTC sleep; and more recently the gliflozin class of diabetes drugs (aka Jardiance, Farxiga) that may help congestive heart failure, mechanism unknown.
Two repurposing drug trials for Alzheimer disease and related dementias (ADRD) had results reported in the last few months. Rasagiline (approved for Parkinson’s) may be positive, and was the subject of a blog post here. Minocycline, an antibiotic in the tetracycline class, had some “compelling results” in clinical multiple sclerosis. R. Howard (UCL) et al performed a two year “pragmatic” trial with minocycline vs. placebo in mild Alzheimer’s, defined clinically with two measures, with over 500 subjects. The results were negative for a significant effect, but perhaps this trial provides a template for future pragmatic (vs. “mechanistic”) repurposing trials.
L. Schneider (USC) wrote the accompanying editorial, and doesn’t say that explicitly, but seems to hint at the idea. I tossed off a letter to the editor of JAMA Neurology, perhaps too rhetorical; it got rejected, so I’ll share it here:
Repurposing drugs for Alzheimer’s: a way forward?
To the Editors:
Schneider provides editorial context for the report in this journal about minocycline, repurposed for an Alzheimer disease (AD) clinical trial [1]. He notes: a) that similar to other recent AD trials, this one skipped through stepwise Phase 1-2-3 testing; b) that “pragmatic clinical trials”, being defined by the National Institutes of Health [2], may have advantages in getting answers more efficiently; and c) that testing repurposed drugs (with their known side-effect profiles), may also yield answers more quickly than new agent trials. He also mentions economic factors.
The author cites recent failures of AD agents in conventional, mechanistic clinical trials, and seems to imply that testing repurposed drugs in pragmatic clinical trials might be a worthy way forward. The National Institute of Aging recently announced a “collaboratory” program to utilize pragmatic clinical trial methodology, but that effort focuses on non-pharmacologic care and health system interventions for dementia patients [3].
Cummings [4] and others have proposed testing repurposed agents in AD; some are proceeding through conventional clinical trials. However, of the 216 actively recruiting AD clinical trials currently listed for the US, only 30% or so involve a repurposed agent.
The editorial raises interesting questions of how pragmatic trial methodology could be adapted and expanded to focus on disease-modifying therapies in AD, and what infrastructure would be needed to proceed, with what comprehensive strategy, organization, and leadership. Given the failures he cited, and the sense of urgency to meet the National Alzheimer’s Project Act deadline of 2025, would Schneider extend his editorial and comment on those questions?
[AlzheimerGadfly]
- Schneider LS. Pragmatic Trials and Repurposed Drugs for Alzheimer Disease. JAMA Neurol. Published online November 18, 2019. doi:https://doi.org/10.1001/jamaneurol.2019.3784
- Weinfurt K. Definition of a pragmatic clinical trial. https://rethinkingclinicaltrials.org/chapters/pragmatic-clinical-trial/what-is-a-pragmatic-clinical-trial-2/. Published online August 25, 2017.
- McGowan M. New research collaboratory designed to spur innovation and improve dementia care. NIH press release, https://www.nia.nih.gov/news/new-research-collaboratory-designed-spur-innovation-and-improve-dementia-care. Published online September 10, 2019.
- Cummings JL and Zhong K. Repackaging FDA-approved drugs for degenerative diseases: promises and challenges. Expert Review of Clinical Pharmacology, 2014, 7:2, 161-165, DOI: 10.1586/17512433.2014.884923