dm+d

Unassigned

New Medicines

DovprelaDrug-resistant or treatment-intolerant or non-responsive multi-drug-resistant tuberculosis - in combination with bedaquiline and linezolid (BPaL regimen)

Information

Dovprela
New molecular entity
Viatris
Viatris

Development and Regulatory status

Licensed but not launched
Licensed but not launched
Licensed but not launched
Yes
Yes
Aug 21Viatris has a named patient access programme to allow access for patients in countries where pretomanid has yet to be launched. In 2019 in England, only 3 people were reported to have XDR-TB. The company has yet to decide whether it will commercially launch Dovprela in the UK [15,16,17].
Jun 21The centrally authorised EU licence for pretomanid has been converted to a GB MA (grandfathered) [13].
Aug 20Pretomanid has been granted a conditional marketing authorisation by the European Commission (EC) for treating highly drug-resistant forms of pulmonary tuberculosis (TB) [12].
Jun 20WHO Consolidated Guidelines on Tuberculosis, Module 4: Treatment - Drug-Resistant Tuberculosis Treatment do not recommend pretomanid based regimens except under operational research conditions in MDR-TB pts with TB that is resistant to fluoroquinolones, who have either had no previous exposure to bedaquiline and linezolid or have been exposed for no more than 2 weeks. This is a conditional recommendation with very low certainty in the estimates of effect. [14]
Mar 20Recommended for EU approval by CHMP - the full indication is "in combination with bedaquiline and linezolid, in adults, for the treatment of pulmonary extensively drug resistant (XDR), or treatment-intolerant or nonresponsive multidrug-resistant (MDR) tuberculosis (TB), see sections 4.2, 4.4 and 5.1. Consideration should be given to official guidance on the appropriate use of antibacterial agents. Pretomanid FGK should be started and monitored by physicians experienced in the treatment of tuberculosis." [11]
Feb 20Still under review by EMA.[7]
Aug 19U.S. Food and Drug Administration today approved Pretomanid Tablets in combination with bedaquiline and linezolid for the treatment of a specific type of highly treatment-resistant tuberculosis (TB) of the lungs [6].
Jun 19US FDA advisory panel recommends approval of pretomanid for treatment of MDR-TB and XDR-TB, in combination with bedaquiline and linezolid. A final decision is expected Q3 2019 [5].
Apr 19Filed in the US with Priority Review, Marketing Authorisation Application accepted by EMA. TB Alliance has licensed Mylan to manufacture and commercialise pretomanid, on an exclusive basis in high-income countries and a non-exclusive basis on low and medium-income countries [3].
Mar 15Pretomanid is in development in Southern Africa by the Global Alliance for TB Drug Development; Novartis was the originator and has an option to commercialise the drug in developed countries. The drug has received orphan designation in the EU (EU/3/07/513) and US [1].

Category

Inhibition of cell-wall synthesis; inhibition of protein synthesis
In 2018, there were 4,655 people with TB in England. an 8.2% decline compared to 5,070 in 2017. The number of people in the drug resistant cohort (confirmed or treated as MDR/RR-TB) decreased between 2017 and 2018(62 vs. 47). [8]
Drug-resistant or treatment-intolerant or non-responsive multi-drug-resistant tuberculosis - in combination with bedaquiline and linezolid (BPaL regimen)
Oral

Trial or other data

Feb 20PIII trials in progress. [9]
Apr 19Two PIII trials are currently in progress using the BPaL regimen - NCT02333799 (Nix-TB, initiated March 2015), and NCT03086486 (ZeNix, initiated Q4 2017); both are open-label and will report findings on an ongoing basis at predetermined milestones [4].
Mar 15A randomised open-label P3 trial (NCT02342886, STAND) has been initiated: the effect of pretomanid combined with moxifloxacin and pyrazinamide is being tested in varying doses and treatment durations in patients with drug sensitive TB, and for 6 months in multi-drug resistant TB. [1]