- Category: Tuberculosis (TB)
- Published on Wednesday, 10 October 2012 00:00
- Written by Liz Highleyman
The novel investigational tuberculosis (TB) drug delamanid, when added to an optimized combination regimen, significantly reduced mortality among patients with multidrug-resistant TB, according to a study published in the September 27, 2012, advance edition of the European Respiratory Journal.
Tuberculosis remains a leading cause of illness and death worldwide. Recent years have seen increased reports of multidrug-resistant Mycobacterium tuberculosis (MDR-TB), which does not respond to standard first-line medications, and extensively drug-resistant TB (XDR-TB), which is resistant to most or all available therapies.
Delamanid (OPC-67683), under development by Japan's Otsuka Pharmaceutical Co., is a nitro-dihydro-imidazooxazole derivative that inhibits synthesis of mycolic acid, an important component of TB bacteria cell walls.
As previously reported, a Phase 2b trial compared delamanid (100 mg or 200 mg twice-daily) vs placebo, both in combination with a World Health Organization-recommended background regimen, which typically consists of 4-5 other drugs. The study demonstrated that delamanid was active against highly-resistant TB, clearing infection in more than 40% of patients.
Vija Skripconoka from Riga East University Hospital in Latvia and colleagues looked at longer-term outcomes among patients who participated in the randomized trial and a subsequent open-label extension study. The delamanid dose arms were combined for analysis according to duration of treatment. This observational study continued for 24 months, with outcomes categorized as "favorable" or "unfavorable."
- 421 of the 481 patients (87.5%) in the original randomized controlled trial were followed and assessed in the observational study.
- 143 patients (74.5%) who received delamanid for at least 6 months achieved favorable outcomes, compared with 126 patients (55.0%) who received delamanid for less than 2 months.
- Mortalitywas reduced to 1.0% among participants who received long-term delamanid, compared with 8.3% among those who received short-term or no delamanid.
- A treatment benefit was also seen among patients with XDR-TB.
This analysis, the researchers concluded, "suggests that treatment with delamanid for 6 months in combination with an optimized background regimen can improve outcomes and reduce mortality among patients with both multidrug-resistant and extensively drug-resistant tuberculosis."
V Skripconoka, M Danilovits, L Pehme, et al. Delamanid Improves Outcomes and Reduces Mortality for Multidrug-Resistant Tuberculosis. European Respiratory Journal. September 27, 2012 (Epub ahead of print).