Lassa fever: addressing knowledge gaps
Addressing knowledge gaps
LF is under-researched, resulting in suboptimal treatment and unacceptably high morbidity and mortality, especially in pregnant women. This, notwithstanding recent initiatives to boost the development of medicinal products for LF.
LF is one of the diseases included in WHO’s R&D Blueprint and the US FDA list of “infectious disease for which there is no significant market in developed nations and that disproportionately affects poor and marginalized populations”, which makes it eligible to the priority review voucher (PRV). CEPI is also supporting the development of LF vaccines.
Still, no drug has ever been registered or even developed for LF. Now, for the first time ever, we are facing the welcome challenge of clinically developing a treatment for LF. However, in order for new treatments to be properly tested against LF, several fundamental questions need to be resolved.
ISARIC is committed to help create a favourable, end-to-end ecosystem for LF clinical research and patient care. This includes:
- closing knowledge gaps on the current standard treatment: ribavirin and supportive care
- create the conditions for treatments to be tested clinically in a rigorous and unbiased way, and for any treatment that is found to be effective and safe, to be available and afforded by the countries and people concerned.
Our activities to evaluate the effectiveness of ribavirin and assess important aspects of Lassa fever case management each contribute to the body of evidence and outputs generated by the WALC project.
Four activities have been undertaken to support the work evaluating ribavirin:
1) a pre-clinical systematic review analysing five domains of evidence (in-vitro, animal, mechanism of action, animal pharmacokinetic (PK), and human PK);
2) a reconstructed analysis of the McCormick trial data;
3) a prospective study of ribavirin PK and PD in Lassa fever patients at Federal Medical Centre Owo (FMCO) in Nigeria in collaboration with FMCO and the Alliance for International Medical Action (ALIMA) and INSERM;
4) a prospective study of cardiovascular function in Lassa fever at FMCO in Nigeria in collaboration with FMCO, ALIMA and INSERM.
To contribute to the evidence around Lassa fever case management, two systematic reviews have been undertaken to characterise the presentation and evolution of Lassa fever and to assess current practices in supportive care. A consultation was conducted with clinicians and researchers with experience in Lassa fever patient care and research to develop a position statement on key components of future Phase III clinical trials.
Supported by the work described above, the WALC project will generate the five principal outputs:
1) a clinical development plan;
2) a pre-positioned clinical trial protocol;
3) a capacity development plan;
4) a target product profile and
5) a value proposition.