Long-acting injectable possible formulations of TB drugs could have several potential benefits, like improved adherence, greater acceptability, and better integration of TB preventive therapy into other treatment programmes, like those for HIV, maternal and child health, said Shobha Shukla.
CROI also shared information on new TB drugs, including long acting injectables, that are in various stages of development: TBAJ-876, a next generation diarylquinoline, is in phase-1 of multiple ascending dose (MAD) study. It has shown improved safety, pharmacokinetics and superior potency. Sutezolid and Delpazolid are new oxazolidinones in phase 2b/2c studies.
DprE1 inhibitors (a novel class of anti-TB agents) are also being developed. OPC-167832, in combination with Bedaquiline and Delamanid, is being evaluated for safety and efficacy of a 4-months regimen for drug-sensitive TB. GSK3036656, a novel translational inhibitor, has been found to be safe and well tolerated after single and multiple doses in its First-Time-in-Human Study for shorter treatment regimen.
Existing TB drug Bedaquiline could be a potential suitable candidate for long acting injectable. One single dose of long acting formulation of Bedaquiline was found to maintain drug and metabolite concentration for up to 3 months in mice. Modelling results expect that this would also be observed in the clinic. New diarylquinolines (like TBAJ-876) may be good candidates for long-acting TB preventive therapy.
Treatment of MDR-TB
Until recently, the standard of care MDR-TB treatment regimen was 18-24 months long and gave a cure of around 50% with highly toxic drugs and painful daily injections given for a minimum of the first 6-months of treatment.
TB PRACTECAL study led by MSF is evaluating a 6 months all oral regimens containing Bedaquiline and Pretomanid in combination with Linezolid, Moxifloxacin and Clofazimine. The study design has 4 groups: one group gets the WHO standard of care regimen; second group gets a regimen of Bedaquiline, Pretomanid, Linezolid, and Moxifloxacin; third group gets a regimen of Bedaquiline, Pretomanid, Linezolid, and Clofazimine; and fourth group gets a regimen of Bedaquiline, Pretomanid, and Linezolid.
As of now, a regimen of Bedaquiline, Pretomanid, Linezolid, and Moxifloxacin, with a tapered dose of Linezolid, has been found to be non-inferior (safe and efficacious) to the standard of care (9-24 months) treatment of rifampicin-resistant TB of the lungs. Outcomes of other regimens are expected to be reported soon.
(Note: You can view every article as one long page if you sign up as an Advocate Member, or higher).
