The World Health Organization issues a position statement on the use of delamanid for multidrug-resistant TB following an expedited review of phase III clinical trial results.
15 January 2018 | Geneva: The World Health Organization (WHO) Global Tuberculosis Programme has released a Position Statement on the use of delamanid in treatment of multidrug-resistant tuberculosis (MDR-TB), following an expedited review of the phase III randomized controlled trial results released at the 48th UNION World Conference on Lung Health in Mexico by Otsuka Pharmaceutical.
"This trial is the first-ever MDR-TB treatment study of its kind to be completed and reported and its findings were thus much-awaited," said Dr Tereza Kasaeva, Director of the Global TB Programme.
WHO acknowledges that the trial was conducted to high scientific standards, guided by an extensive and detailed study protocol, and with broad geographical distribution of study sites in seven countries (Estonia, Latvia, Lithuania, Republic of Moldova, Peru, the Philippines, and South Africa).
Trial participants received either delamanid or a placebo for six months, added to an optimised, longer background MDR-TB regimen designed according to WHO recommendations. Participants were randomised to receive either delamanid or placebo in a ‘blinded’ fashion, i.e neither they nor the treating physicians were aware of whether the medicine added to the MDR-TB regimen was active delamanid or an inactive placebo.
Overall, cure and mortality rates were similar in trial participants who received delamanid and in those who received the placebo on top of the optimised background MDR-TB regimen. The trial thus did not confirm the efficacy findings of earlier studies. However, no additional or new safety concerns were identified, providing reassurance of the safety of delamanid relative to many of the other second-line medicines used for MDR-TB treatment.
WHO is advising national TB programmes and other stakeholders to only add delamanid to a longer MDR-TB regimen when the regimen cannot be composed according to WHO recommendations, eg. when drug intolerability or drug resistance requires changes. When an effective and well-tolerated longer MDR-TB regimen can be otherwise composed, the addition of delamanid may not be warranted.
"MDR-TB trials are notoriously complex and difficult to do," said Dr Karin Weyer, Coordinator of Laboratories, Diagnostics and Drug Resistance at the Global TB Programme. "We therefore commend the efforts of everyone involved, most importantly the MDR-TB patients who consented to participate. Research on the role of delamanid in MDR-TB treatment is important and should continue. In particular, the use of delamanid in MDR-TB regimens compromised by drug resistance or drug intolerability should be pursued".
Delamanid should be retained in country guidelines, national essential medicine lists and procurement options, but MDR-TB treatment algorithms (and therefore procurement estimates) may need adjustment in view of the trial outcomes.
WHO is currently also conducting an expedited review of the STREAM Stage 1 interim results, another phase III randomized controlled trial, comparing a standardised shorter MDR-TB regimen to a longer MDR-TB regimen designed according to WHO recommendations.
Further to the expedited reviews of these two trials, WHO will conduct an extensive review of its MDR-TB policy guidelines this year. This will include a review of observational data for bedaquiline, delamanid and the shorter MDR-TB regimen conditionally approved by WHO, as well as a reassessment of the role of individual second-line medicines in MDR-TB regimens based on the latest patient and laboratory data.