Researchers from the department of Chemistry & Pharmaceutical sciences (CPS) at the Vrije Universiteit Amsterdam team up with The Centre for Snakebite Research & Interventions at the Liverpool School of Tropical medicine (LSTM) on a Phase II clinical trial of 5 Meuro awarded by Open Philanthropy. This multi-center Phase II drug trial will test the potential of two repurposed drugs for use in treating snakebite envenoming.
Snakebite envenoming is a priority neglected tropical disease (NTD), responsible for >100,000 deaths and 400,000 disabilities annually, predominantly in low- and middle-income countries (LMICs).
The only current treatment, animal-derived antivenom, is costly, difficult to administer, and not readily available in rural areas where the burden of snakebite is highest. The new trial seeks to address these issues by evaluating two innovative oral drugs that could offer a far more accessible and affordable alternative, or a complimentary therapy.
Dr. Jeroen Kool, head of the venom research group at CPS, says "Venomous snakebites can result in horrible outcomes for the victims including serious permanent morbidities and even death. These snakebites are mostly happening to poor people living in rural, resource-poor, settings in the (sub)-tropics. As such, snakebite envenoming has long been a neglected public health issue. This funding will allow us to move forward with clinically evaluating two very promising small molecule drug candidates.”
Dr. Sofia Moco, researcher at CPS and recognized expert in metabolism studies, says “One of these compounds is a marketed, thus proven safe, drug for heavy metal poisoning, while the other one successfully passed clinical Phase I and II trails as anticancer drug candidate, thereby also proving to have adequate safety profile. These two drugs will now be tested for the NTD snakebite aiming to provide a suitable, more accessible treatment. They can be easily administered shortly after a bite occurs, and hopefully prevent major pathology or loss of life. If the trials are successful, these drugs can have a major impact for future treatment of snakebite victims."
Jeroen and Sofia will be responsible for the pharmacokinetics (PK) within the trials.
The trials will focus on the treatment of envenoming from vipers, the snake family responsible for most snakebite-related deaths and disabilities worldwide. Viper venoms contain snake venom metalloproteinase (SVMP) enzymes, which cause severe bleeding, clotting disorder and tissue damage. Both drugs to be used in the trial have been shown in preclinical studies to inhibit these enzymes, preventing the deadly effects of envenoming.
The trials are planned in partnership with leading scientists at the Fundação de Medicina Tropical in Brazil and the Kumasi Centre for Collaborative Research in Ghana, where venomous snakes such as Bothrops atrox (lanceheads) and Echis ocellatus (saw-scaled vipers) are prevalent. The trial consortium also contains scientists from the University of Liverpool, Cambridge University and KEMRI-Wellcome in Kilifi, Kenya.
Dr Michael Abouyannis, clinical lead on the project for LSTM, said: “Undertaking snakebite trials is complicated, and this project will be no exception, but, particularly with the support of such a skilled and passionate group of partners, we are confident it will be a success. The two orally administered treatments we are assessing show great promise and could truly revolutionise the treatment of snakebite. I think I speak for everyone involved when I say I’m excited to see the trial’s results.”
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 such as this represents a pivotal step towards this goal.