Researchers from Liverpool School of Tropical Medicine (LSTM) have taken a significant step towards transforming snakebite treatment with the completion of a Phase I clinical trial for a new oral treatment for snakebite.
The study, conducted by researchers from the Centre for Snakebite Research & Interventions (CSRI) at LSTM and the Kenya Medical Research Institute (KEMRI) Wellcome Trust Research Programme in Kilifi and published in the journal eBioMedicine, shows that the drug, unithiol, is safe, well tolerated, and easy to administer in remote rural clinics, paving the way for its development as a field-ready treatment.
Unithiol is already approved for treating heavy metal poisoning but was identified for study in the treatment of snakebite envenoming due to its ability to neutralise snake venom metalloproteinases (SVMPs). These zinc-based toxin components, found in the venoms of vipers and many other snakes, are responsible for causing severe tissue damage and life-threatening bleeding in snakebite patients.
Snakebite envenoming remains a major global health challenge, causing over 140,000 deaths a year, mainly in rural Sub-Saharan Africa, Latin America and Asia. Current antivenom treatments are costly, can cause severe side effects, and must be administered intravenously in hospital settings, barriers that delay life-saving intervention.
Dr Michael Abouyannis, the study's lead author and clinical researcher at LSTM, said: "The animal derived antivenoms used today are based on 100-year-old principles. It's a sign of how neglected snakebite is as a health concern that these antiquated treatments are still being used today. Small molecule therapeutics, such as unithiol, have the potential to be safer and cheaper and can be taken easily as a pill.
"This phase 1 trial, which wouldn't have been possible without the support of Professor Hamaluba and the team at KEMRI-Wellcome in Kilifi, has shown that unithiol is safe even at the high doses that we believe will be needed to treat snakebite, so we could be on the cusp of bringing snakebite treatment into the 21st century and vastly improving patient outcomes."
Preclinical research by LSTM scientists previously demonstrated that unithiol could prevent the worst effects of venom and potentially save lives. The phase 1 clinical trial assessed different doses of unithiol in oral and intravenous forms. All showed no serious side effects, even at the maximum dose, and analysis of participants' blood found that the drug was rapidly absorbed and present at levels expected to inhibit snake venom toxins.
Based on these findings, the LSTM team has secured funding to advance unithiol to phase 2 clinical trials, where the drug will be tested in patients who have been bitten and envenomed by snakes. If successful, unithiol could be rapidly deployed in rural clinics and first-aid settings, buying snakebite victims valuable time to get to a hospital and reducing the severity of envenoming.
Professor Nicholas Casewell, Director of the CSRI at LSTM, said: "Snakebites often occur in remote, rural locations where the nearest hospital can be many hours away. As we move into phase 2 of clinical trials for unithiol, we move closer to a world where snakebite envenoming can be treated in a clinic just minutes away from a patient.
"While unithiol may not be a cure by itself, we hope that it will prevent the worst effects of snakebite envenoming and buy victims valuable time to get to a hospital, thereby reducing their risk of death or disability."
Developing safe, affordable, and easy-to-administer treatments like oral drugs could be critical in achieving the World Health Organization's (WHO) goal to halve snakebite-related deaths and disabilities by 2030. Evaluating their safety and efficacy in trials like this represents a pivotal step towards this goal.