The results of the Phase II clinical trial were published in The Lancet Infectious Diseases in November 2024 and showed that treatment with either of the two dose levels of fosravuconazole was not superior to itraconazole, and the two dose levels had a numerically lower efficacy. However, fosravuconazole presented no new safety signals, and its lower pill burden and reduced risk of drug-drug interactions compared with relatively expensive and inaccessible itraconazole suggests further research into effective treatments with a shorter duration and higher cure rate, without the need for surgery, is warranted.

The results of the Phase II clinical trial were presented at the 13th European Congress on Tropical Medicine and International Health (ECTMIH), held in November 2023 in Utrecht, Netherlands. The clinical study report was finalized and results are expected to be published in 2024. The long-term follow-up study assessing the recurrence rate of mycetoma in clinical trial participants in the Phase II trial was stopped in 2023 due to socio-political unrest in Sudan. A total of 51 participants were included in the follow-up study. Recurrence rates remained low and no serious adverse events were reported.

The database lock for the Phase II clinical trial was conducted in March 2022. The top-line results were presented at the 21^st Congress of the International Society for Human and Animal Mycology (ISHAM), held in September 2022 in New Delhi, India. The clinical study report is under review and expected to be finalized in early 2023.

To determine the long-term post-treatment recurrence of eumycetoma, an observational study has begun at the Mycetoma Research Center in Khartoum, Sudan. It will follow patients who did not have a recurrence by the end of the Phase II clinical trial.

Although challenged by the COVID-19 pandemic which resulted in a country-wide lockdown in Sudan, patient follow-up continued in 2021. The study was reviewed by the data and safety monitoring board in late 2021, and it was decided that the study could be stopped, and the results analysed in early 2022. A strategy was developed to register fosravuconazole in Sudan, initially on a compassionate or conditional basis in advance of full registration. In addition, an access strategy is under development.     

By March 2020, 104 patients had been enrolled in the study, but the target was to enrol 165 patients by the end of the year. Recruitment was put on hold while a second interim analysis is prepared. After this analysis is completed in mid-2021, the clinical trial may be terminated or may progress until full completion of the recruitment is concluded in 2022. Discussions with regulatory authorities in Sudan to obtain conditional approval for compassionate use of the drug will also begin in 2021.

The first-ever double-blind study to determine whether the new chemical entity fosravuconazole could be an effective and affordable treatment for eumycetoma is ongoing. By January 2020, 101 patients had been enrolled in the study, which should reach the targeted enrollment of 165 patients by the end of 2020. A Data and Safety Monitoring Board (DSMB) meeting was held in 2019 after the study reached the threshold for interim analysis (84 participants). The DSMB reviewed study data and decided to continue with all three treatment arms (200 mg vs 300 mg of fosravuconazole weekly vs daily itraconazole).

Following slower than anticipated recruitment, a protocol review and amendment was conducted in 2018 to extend the inclusion criteria in relation to lesion size and site, and age range of participants. By January 2019, 84 patients had been enrolled, reaching the threshold for interim analysis. This analysis will determine which of two treatment arms will be retained for the remainder of the trial (200mg vs 300mg of fosravuconazole weekly).

After receiving regulatory and ethical approval in March 2017, the Mycetoma Research Centre, a WHO Collaborating Centre, began recruiting patients into the first-ever double-blind, randomized Phase II/III clinical trial for eumycetoma. The clinical trial, which plans to recruit 138 patients, evaluates the efficacy of the anti-fungal fosravuconazole in moderate lesions in comparison with the current treatment, itraconazole.

The primary objective of this single-centre study conducted in Sudan is to demonstrate the superiority of fosravuconazole over itraconazole after 12 months’ treatment. By the end of 2017, 20 patients had been enrolled into the trial, a pace of enrolment that was slower than anticipated. In 2018, a satellite site will be established to screen more patients and refer them for treatment and care.

Protocols of the phase II/III aiming at assessing the comparative efficacy, safety, and tolerability of fosravuconazole in patients with eumycetoma caused by Madurella mycetomatis were finalized in 2016 and recruitment of patients (with a target of 136 participants) should start early 2017. An interim analysis will be conducted at three months.

DNDi is currently preparing for a Phase II/III randomized controlled trial that will be conducted with the WHO Collaborating Centre on Mycetoma in Khartoum to study the efficacy of fosravuconazole in moderate lesions in comparison with the current treatment, itraconazole. The primary objective of this double-blind, randomized, single-centre study will be to demonstrate superiority of fosravuconazole over itraconazole after 12 months’ treatment in patients with eumycetoma caused by Madurella mycetomatis.