| dc.description.abstract | Few innovative therapies for neglected diseases, such as snakebite, are being developed for LMICs. Due to regulatory voids for specific treatments in the current regulatory system, uncertainty for developers pursuing the development of these treatments arises. Recently the largest manufacturer of qualitative snake venom has withdrawn from the African market, leading to an unmet medical need. Monoclonal antibodies could be a viable alternative to the current treatments for snakebite, but the regulatory void currently disincentivizes development. However, a monoclonal antibody replacement was recently developed and approved for Rabies, despite the presence of a regulatory void. Therefore, this research retrospectively and prospectively analyzed the regulatory discussion for the two cases by interviewing stakeholders and experts in the field in order to identify which points of discussion are present in the regulatory approval process of both treatments. Insights were then linked to principles for the design of facilitated regulatory pathways in order to examine how these principles are viewed and how these can be used in the regulatory discussion to facilitate regulatory approval.
Three main points of discussion were found for both cases: (1) Regulatory categorization of a treatment, (2) A difficult to define Standard of car, and (3) How to correctly access the efficacy of the treatment. In a comparison, the potential categorization of the treatment and heterogeneity in the standard of care were perceived to have more severe consequences for the access to the snakebite treatment than the rabies treatment. The correct efficacy assessment was discussed evenly in both cases as both cases had various points of uncertainty. The discussion provided implications for the formulation of a possible facilitated regulatory pathway for mAb antivenom in LMICs. Moving the burden of clinical benefit and evidence to the post-authorization phase could be used in order to speed the time to market for snakebite victims without access to specific treatment. Increasing the level of communication and commitment between the regulator and developer could be used in order to enhance the transparency in the regulatory pathway to counteract the strategic use of the ambiguity surrounding the standard of care. Sophisticated patient stratification methods, pan-specific antivenom, and the use of workable and verifiable surrogate clinical endpoints could be used to correctly assess the efficacy. Finally, increasing the role of medicines’ effects on surrogate endpoints, allows expedited access based on preliminary clinical data by counteracting uncertainty. | |
