Introduction and Background of the Project

Introduction

Fosravuconazole, an oral azole antifungal treatment discovered by Eisai and approved in Japan for onychomycosis, offers a safe, well‑tolerated, and patient‑friendly treatment option for eumycetoma. Following consultations with the World Health Organization’s (WHO) Coordinated Scientific Advice (CSA) team and the Neglected Tropical Diseases (NTD) department, this project will conduct a multi‑country, open‑label clinical trial in Kenya, Senegal, and India to generate additional evidence for the WHO recommendation and regulatory registration of fosravuconazole for eumycetoma. The project builds on results from a GHIT‑funded Phase II randomized clinical trial in Sudan, which demonstrated satisfactory efficacy and a favourable safety profile. The new trial will address limitations of the earlier study, including small sample size, single‑country population, and limited pathogen diversity.

Project Objective

The project will generate clinical evidence across diverse endemic regions – Senegal, Kenya, and India – to confirm the efficacy, safety, and pharmacokinetics of fosravuconazole, including against causative organisms beyond Madurella mycetomatis. This follows Phase II results showing good efficacy and a favourable safety profile of fosravuconazole, and aims to generate further scientific evidence.

To support global introduction, the project will also implement a comprehensive regulatory strategy, including engagement under consideration with several agencies including the WHO and Swissmedic, and prepare for the WHO Pre-Qualification (PQ).

Project Design

A multi-country, open-label prospective clinical trial will be conducted in Kenya, Senegal, and India to evaluate the efficacy, safety, and pharmacokinetics of fosravuconazole 200 mg in patients with eumycetoma. The trial uses a non‑comparative, open‑label design developed in consultation with the WHO, to accelerate access to a promising therapy with advantages over currently available treatments. Participant recruitment will take approximately 12 months, followed by 12 months of treatment and follow‑up for enrolled patients to ensure complete and reliable clinical data in line with ethical and scientific standards.

To support regulatory readiness, DNDi and Eisai will seek scientific advice from a stringent regulatory authority, currently planned with Swissmedic through the Marketing Authorisation for Global Health Products (MAGHP) procedure, which enables participation from endemic countries and the WHO PQ team. Together, DNDi and Eisai will develop a global regulatory strategy to facilitate WHO recommendation and registration in endemic countries, supported by early consultations with the WHO.

How can your partnership (project) address global health challenges?

Eumycetoma is a severely neglected tropical disease that causes chronic, destructive infections, often leading to disability, amputation, loss of income, and social stigma. It affects tens of thousands of people in low‑income rural communities across Africa, Asia, Latin America, and parts of Europe, with the highest burden in the so-called ‘mycetoma belt’ between latitudes 15° S and 30° N. Although underreported, global estimates suggest that more than 100,000 people may be living with the disease, with thousands of new cases annually. Despite its significant impact, current treatments remain limited, often toxic, and poorly tolerated. To the best of our knowledge, no drug for mycetoma has been evaluated through randomized controlled trials in patients diagnosed with the disease. Our study in Sudan is the first such trial to address this critical gap.

This project tackles a major global health challenge by progressing fosravuconazole toward regulatory approval and wider availability. By doing so, it aims to provide patients with an effective and more patient-friendly therapy with good safety profile also supported by Phase II clinical results from Sudan. As the only active drug development effort targeting eumycetoma, the project responds to an urgent unmet need, offering the potential to reduce disability, prevent amputations, and improve quality of life for highly vulnerable populations.

What sort of innovation are you bringing in your project?

The project introduces innovation by advancing fosravuconazole, a new oral antifungal treatment specifically designed to meet the needs of patients in low‑resource, endemic settings. Unlike current therapies that require long‑term daily dosing and are often poorly tolerated, fosravuconazole enables once‑weekly dosing, and does not require food for optimal absorption, with reduced risk of drug-drug interactions, supporting better adherence in rural communities.

The drug’s pharmacokinetic profile enables simplified dosing and improves adherence – critical factors for patients living in the regions most affected by the disease. Its low pill burden also lowers distribution and patient costs, making it a scalable and affordable treatment.

By offering a regimen that is easier to administer, safer, and more suited to real‑world conditions, the project aims to deliver a patient‑centered and practical innovation that can improve treatment outcomes and strengthen the ability of health systems to manage neglected tropical diseases.

Role and Responsibility of Each Partner

DNDi oversees overall project coordination, managing implementation, timelines, and reporting. As the clinical trial sponsor, DNDi will lead the multi‑country open‑label trial with its subcontracted partners. Its responsibilities include developing and submitting study protocol and documents for national ethics and regulatory approval; overseeing trial operations such as quality assurance, data management, pharmacovigilance, and clinical study reporting, and coordinating partners on molecular diagnostics, technology transfer, and PK/PD analyses.

Eisai supports protocol development and ensures supply of fosravuconazole by packaging existing batches, producing new batches, and shipping them to study sites.

Together, DNDi and Eisai develop global regulatory strategy and lead stakeholder engagement, including engaging with regulatory authorities as well as the WHO’s PQ and NTD teams to facilitate global recommendation.