According to research reported in The Lancet, oral fexinidazole is safe and effective for treatment of late-stage human African trypanosomiasis, a tropical disease caused by Trypanosoma brucei gambiense, compared with nifurtimox/eflornithine combination therapy.
Between October 2012 and November 2016, 394 patients aged ≥15 years with late-stage trypanosomiasis were included in a randomized phase 2/3, open-label noninferiority trial conducted in dedicated, disease-specific treatment centers in the Democratic Republic of Congo and the Central African Republic (ClinicalTrials.gov Identifier: NCT01685827).
A total of 264 patients were administered fexinidazole 1800 mg once daily on days 1 to 4 and at 1200 mg on days 5 to 10.
Oral nifurtimox 15 mg/kg/d was given to 130 patients three times daily for 10 days, along with 2-hour infusions of eflornithine 400 mg/kg/d twice daily on days 1 to 7. The primary end point was success at 18 months, deemed as patients being alive, having no evidence of trypanosomes in any body fluid, not requiring rescue medication, and having a cerebrospinal fluid white blood cell count ≤20 cells/μL.
Success at 18 months was observed in 91% of patients receiving fexinidazole and 98% of patients receiving combination therapy. The difference between groups was –6.4% (97.06% CI: -11.2 to -1.6; P = .0029), which was within the acceptable 13% margin. No difference in the proportion of treatment-related adverse events was noted: 81% in the fexinidazole group compared with 79% in the combination-therapy group.
Although a difference in favor of combination therapy was noted, the use of oral fexinidazole was deemed safe and effective and is currently the only short-course monotherapy option available. Therefore, as experts have stated, fexinidazole could address the need for “easy to use and effective” treatment options for trypanosomiasis.
This study was funded by the Drugs for Neglected Diseases initiative.
Mesu VKBK, Kalonji WM, Bardonneau C, et al. Oral fexinidazole for late-stage African Trypanosoma brucei gambiense trypanosomiasis: a pivotal multicentre, randomised, non-inferiority trial. Lancet. 2018;391(10116):144-154.