Universal treatment of multi-drug resistant TB is possible within current budgets with generic production
1 August 2016. Related: Conference reports, TB coinfection, TB 2016 Durban.
Polly Clayden, HIV i-Base
Generic production could make novel multi-drug resistant tuberculosis (MDR-TB) regimens available for US $53-507 per treatment course according to data presented at TB2016. [1]
High drug prices contribute to slow progress with scaling up treatment of MDR-TB with novel regimens worldwide. Dzintars Gotham and colleagues from Imperial College London, Howard University, Washington and St Stephens Centre, London showed that competitive generic production could make universal coverage possible within current budgets.
This group have previously used similar methodology to look at cost of generic production of HIV and HCV treatment – they first presented data from the MDR-TB treatment production costs evaluation last year at EACS. [2]
For moxifloxacin, linezololid and clofazimine, the investigators estimated prices by obtaining the costs of active pharmaceutical ingredients (API) from Indian export data. For bedaquiline, delamanid and pretomanid (newer drugs so no comprehensive export data) they estimated the costs using those of synthetic processes and raw materials. To estimate generic prices, the investigators combined API per kilogram costs with dosage, manufacturing costs (including excipients, cost of tableting and packaging) and a 10-50% mark up.
They collected current drug prices from the Global Drug Facility (GDF) website, where these were available. For delamanid they used the recently announced price from the originator. As the price for pretomanid is yet to be announced, the investigators conservatively assumed pricing at their highest generic estimate.
The analysis revealed that novel regimens could be available for US $53-507 per treatment with generic production. In 2014, US $173 million were spent on second-line TB drugs through the GDF. Assuming this budget, the investigators calculated that estimated drug prices would allow the purchase of: 86-170% more STREAM B treatments (at least 202,000 more treatment courses); 401-679% more STREAM C (at least 386,000 more treatment courses); 406-689% STREAM D (at least 529 more treatment courses); 1362-3007% more MDR-END (at least 319 more treatment courses); 23-164% more PaMZ (at least 282,000 more treatment courses). See Table 1.
| Regimen | Current lowest cost | Estimated generic cost | Current number of treatment courses afforded | Estimated number of treatment courses afforded |
|---|---|---|---|---|
| STREAM arm B*, 9 months (moxifloxacin, clofazimine, ethambutol, pyrazinamide, isoniazid, prothionamide, kanamycin) | $734 | $272-395 | 236, 000 | 438, 000 to 636, 000 |
| STREAM arm C, 9 months (levofloxacin, clofazimine, ethambutol, pyrazinamide, isoniazid, prothionamide, bedaquiline) | $1,799 | $231-359 | 96, 000 | 483, 000 to 749, 000 |
| STREAM arm D, 6 months (levofloxacin, clofazimine, pyrazinamide, isoniazid, kanamycin, bedaquiline) | $1,325 | $168-262 | 131, 000 | 660, 000 to 1,030, 000 |
| MDR-END, 20 months (delamanid, linezolid, levofloxacin, pyrazinamide) | $7,408 | $ 238-507 | 23, 000 | 342, 000 to 726, 000 |
| PaMZ 6 months (pretomanid, moxifloxacin, pyrazinamide) | $140 | $53-114 | 1, 236,000 | 1, 518, 000 to 3, 264, 000 |
* Newly recommended WHO shortened 9-month regimen
The investigators concluded that at existing prices current budgets are not sufficient to afford universal treatment of MDR-TB with novel regimes. But generic production could make novel regimens available for US $173 million – the amount spent on second-line drugs at current prices procured by the GDF in 2014.
Comment
Earlier findings from this excellent analysis were presented in October at EACS. But unlike that from HIV and HCV communities, so far the reaction from those working on TB has been lukewarm.
The annual incidence of MDR-TB is only 480,000, so there will not be the potential economies of scale seen with generic drugs to treat adult HIV and HCV.
Optimising treatment of paediatric HIV might be more analogous – where the number of priority drugs, formulations and regimens have had to be vastly pruned (and still needs more pruning) – to make sufficient volumes possible and procurement simpler.
References:
- Gotham D et al. Affordability of comprehensive MDR-TB treatment with novel regimens, at current prices versus estimated competitive generic prices. TB2016. 16-17 July 2016. Durban, South Africa. Poster abstract P42.
- Gotham D et al. Target prices for novel treatments for drug-resistant tuberculosis. 15th European AIDS Conference (EACS). 21-24 October 2015. Barcelona, Spain. Oral abstract 351.