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Colchicine: COVID wonder drug? Or just bad science?

Since the early months of the pandemic, researchers have been investigating the effects of repurposing already available drugs for the treatment of COVID-19.

Protease inhibitors, reverse transcription inhibitors, baricitinib, and camostat mesylate have all been studied for potential repurposing, with varying results. Earlier this year, the authors of the international Colcorona study generated much fanfare when they purported to add another drug – colchicine – to the list.

Typically used to treat inflammation, including gout flare-ups, colchicine is a widely-prescribed alternative for those unable to tolerate NSAIDs. The drug, which is derived from the autumn crocus (Colchicum autumnale) and dates back to 1500 BC, was alleged to have reduced the risk of hospitalisation by 25% for patients with a positive naso-pharyngeal PCR test for COVID-19. The need for mechanical ventilation, meanwhile, was reduced by 50%, and deaths by 44%.

The Colcorona study’s authors claim their findings make colchicine the world’s first oral drug with the potential to treat non-hospitalised COVID-19 patients. As a potent inhibitor of tubulin polymerisation and neutrophil production of free radicals, colchicine suppresses caspase-1 activation and the release of pro-inflammatory cytokines interleukin-1β and IL-18, dampening the effects of an accompanying ‘cytokine storm’, which has been associated with COVID-19 mortality.

“Our research shows the efficacy of colchicine treatment in preventing the ‘cytokine storm’ phenomenon and reducing the complications associated with COVID-19,” said Dr. Jean-Claude Tardif, Director of the MHI Research Center, Professor of Medicine at the Université de Montréal and Principal Investigator of the Colcorona trial. “We are pleased to offer the first oral medication in the world whose use could have a significant impact on public health and potentially prevent COVID-19 complications for millions of patients.”

‘Bad science’

Respondents to the Colcorona study have criticised it as “another example of bad science through press release during the COVID-19 pandemic,” citing the fact that neither mortality nor hospitalisation due to COVID-19 were “statistically different” between recipients of colchicine and those who received a placebo. This may seem in stark contrast to the aforementioned statistics provided by the study’s authors, but these were in fact derived from the difference between the two groups – colchicine and a placebo – in terms of the study’s primary endpoint (death or hospitalisation due to COVID-19 infection in the 30 days following randomisation), which were 4.7% and 5.8% respectively.

The study’s authors have issued responses to the many questions generated by their findings, claiming that, in the context of the pandemic where no therapy is currently available to prevent hospitalisations, the benefits of a safe, inexpensive and orally administered medication are clinically important: “The consistency of the results for the composite primary endpoint, its components and the secondary endpoints for both the overall population and that with PCR-confirmed COVID is clinically persuasive in our opinion.” They also noted the results of a prevs trial which found that there may be “a role for colchicine in the treatment of patients with coronavirus disease 2019.”

The way forward

There can be no denying the urgent need for therapeutics targeting COVID-19. Statistically, even a moderate reduction in the number of serious cases, i.e. those requiring hospitalisation or ventilation, could lead to thousands of lives being saved, not to mention an appreciable reduction in the load placed on medical care systems. The results of the Colcorona study, however, are contested.

At LGC, we are dedicated to supporting science for a safer world. Never in recent history has this been a more public cause than in the wake of the COVID-19 pandemic. Through our Toronto Research Chemicals portfolio, we supply an extensive range of products designed to support researchers working to discover potential repurposing strategies to target COVID-19. Our range of colchicine products includes high-quality intermediates, impurities, metabolites, and stable labelled isotopes, and our custom synthesis solution allows for the development of new synthetic routes to support your research, whatever your goals.

Get in touch today to find out more, or head to our website to browse our catalogue.

LGC – science for a safer world.

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