Snakebite Envenoming Medicines Database

Given the nascent and nuanced field of SBE R&D, we sought to use the broadest possible inclusion criteria and incorporated various types of molecules or biologics tested for or used with direct action against snake venom toxins with product development in mind. Products and candidates could be applicable for use in any context, including high-income countries and low- and middle-income countries.

For inclusion in the dataset, products and candidates needed to:

• Be synthetic or natural small molecules (drugs) or immunoglobulin (animal plasma/serum-derived or recombinant) or non-immunoglobulin- (animal, natural or recombinant) based biological therapies (biologics), with no restrictions: entries could be entirely new chemical or biological entities (NCEs) or existing/repurposed/label extensions
• Have a direct inhibitory action on snake venom toxins, neutralising venom components to have a therapeutic effect on snakebite envenoming
• Have evidence of research and development (candidates) towards product development, or use (products) at any point since 2015
• Be either investigated for potential clinical use and/or used currently in clinical treatment of snakebite envenoming from WHO medically important category 1 or 2 snakes (or both) only

Specific exclusions were:

• Adjunct and supportive therapies which only modify responses to action of and symptoms caused by snake venom toxins
• Devices, diagnostics and other non-medicine-related biomedical products with an indication for SBE
• Basic and fundamental research which was not geared towards product development

To develop this database we:

1. Identified and validated products and candidates through multiple sources that are or were in use or in development since 2015;
2. Collected information on the products’ and candidates’ preclinical and/or clinical development, and associated data;
3. Researched additional context around the products and candidates (e.g., immunisation/production strategy, paraspecificity, region of use and/or registration etc.) to build out multi-field entry profiles;
4. Validated and sense checked candidate profiles through independent, external reviews by clinical research and subject matter experts in the field.

Following database completion, a series of internal and external, independent reviews were undertaken to clean and validate the data. Internally, each candidate and product profile was reviewed for content, consistency, and logic by a minimum of two individuals. Data cross checking and cleaning was conducted in a rigorous, sequential manner. Some steps served to clean and standardise the data, while others were intended to identify content or subject matter error. An external review was also undertaken. We sought independent, specialist input from members of the project’s expert advisory group. The entire database was reviewed to validate entries or identify known missing candidates or products; review essential, standard labels; provide additional industry information to fill gaps as appropriate; and for each, recommend corrections, improvements, or additional details. External review was undertaken between June and July 2022.

Due to the nuanced nature of the SBE medicines R&D landscape and inherent biases and weaknesses in available information, the database has some limitations. Firstly, due to the proprietary nature of (and lack of publicly available information on) many, particularly preclinical, candidate investigations, we anticipate the data may have gaps with respect to the full body of research. We also acknowledge that nearly all the data sources used rely on self-reporting by investigators, which have their own inherent limitations, including potential for reporting biases arising from changes in adherence and utilisation over time, as well as publication biases towards positive results. Other data may have been overlooked due to English-language bias, especially for Central and South American products where much of the available information was in Spanish and Portuguese. Lastly, information overall – particularly for available products – was often extremely hard to obtain, sometimes dictating that we rely heavily on secondary sources to fill gaps.

Secondly, our deliberate decision to be as inclusive as possible means also that within the database we are not always comparing like with like. Examples include: projects and programmes of work versus a clear lead drug candidate; alternative animal models giving rise to genuine novel biologics (e.g., chicken antibody and antibody fragment candidates) versus alternative animal models as precursor research to more traditional approaches (e.g. some rabbit antisera candidates, also acknowledging some publish findings with this type of research and others don’t); and single molecules or isolates under investigation versus combined related series of molecules or biologics. Despite these differences, this approach has enabled us to present the most comprehensive database of molecules, biologics and streams of work with therapeutic potential possible, fulfilling our intention to capture what is going on in the SBE R&D landscape in the broadest sense.

Thirdly, direct action on snake venom toxins sensu stricto was a major inclusion criterion for this undertaking. This meant, however, that some R&D with alternative mechanisms of action – but similar outcomes and therapeutic potential – were necessarily omitted.