Price of MDR TB drugs could be greatly reduced with competitive generic manufacture

1 December 2015. Related: Conference reports, Treatment access, TB coinfection, EACS 15 Barcelona 2015.

Polly Clayden, HIV i-Base

Competitive large-scale generic manufacture could mean that at least 10 times more multi-drug resistant TB (MDR-TB) cases could be treated within current procurement costs, according to an analysis presented at EACS 2015. [1]

Andrew Hill and colleagues from Imperial College London, Howard University, Washington, Chelsea and Westminster Hospital, and Liverpool University, performed the study. The authors used methodology previously developed to calculate the cost of antiretrovirals and hepatitis C and B drugs.

New TB drugs are being developed for shorter course treatment and MDR-TB. Current MDR-TB treatment can cost more than $1000 per course in low-income countries with far higher prices elsewhere. The authors noted that such prices strain health budgets. The study calculated target generic prices for novel TB treatments.

Key TB drugs were categorised as:

• Group 1-3, already generic – clofazimine (although patent expired, only one manufacturer)
• Group 4, basic use patent expiring from 2014 (moxifloxacin, linezoloid, sutezoloid)
• Group 5, patent expiry 2016-2013 (pretomanid, delamanid, bedaquiline)

The authors obtained costs of active pharmaceutical ingredients (API) for all group 1-4 drugs using an online database reporting cost per kilogram (kg) of exported API. [2] They also collected prices by country and from the Global Drug Facility (GDF).

They estimated prices for linezolid, moxifloxacin, and clofazimine using algorithms combining dosage with per-kg prices of API and excipients and adding on formulation, packaging and a typical generic profit margin.

Estimates for sutezolid and posizolid synthesis were projected from those for linezolid. Sutezolid is structurally similar to linezaloid and has similar costs of production. Posizolid is structurally similar but has production costs three times higher than linezolid.

Target prices for bedaquiline and delamanid were calculated by analysing chemical synthesis, costs of raw materials and production. The authors assumed production costs of pretomanid to be four times that of delaminid, based on its chemical structure.

They projected lower and higher target prices for each of the drugs. The lower price was estimated using: 1 cent per pill for formulation; 10 cents per month for packaging; and 10% profit margin. The higher target price used: 4 cents per pill for formulation; 35 cents for packaging; and 50% profit margin.

Volume demand assumptions for the lower and higher target prices respectively were: greater than one million treatment courses per year (validated from GDF price comparisons) and greater than 100,000 treatment courses per year (validated from hepatitis C analysis).

The analysis revealed current GDF prices of group 1-4 drugs that mostly fell within calculated target prices with the exception of moxifloxin (GDF price $18.1/month compared with target price $3.5-9.4).

The price of moxifloxin varied enormously from $806/month (Bayer) and $232 (generic) in the US to $19 in Russia.

Group 5 drugs that are still patent protected or not yet approved for use in TB treatment had the highest current prices and the greatest potential for reduction. See Table 1.

*Little information available on pricing of delaminid – price in Japan quoted.

The price of linezolid ranged from $4,298/month for the Pfizer drug in the US to $70 for an approved generic version in India (and $17 for a non-approved generic).

Bedaquiline has tiered pricing of US$4,532, US$453 and $136 for high-, middle- and low-income countries respectively – compared with the high and low target prices ($8.8-16.4).

Prices for delamanid were available for the US, Germany and Japan, US$4,510, US$4,258 and US$3,108 respectively – compared with generic high and low prices ($3.5-8.6).

Using these prices, the cost of treatment courses containing bedaquiline in two arms the STREAM study, [3] could be fall from $871-1834 to $176-422 per course. For three drug regimens the generic price could be $86-389.

The authors explained that the analysis assumes that MDR-TB drugs can be ordered centrally at low prices. Currently multiple drugs are ordered in small quantities nationally. Achieving low prices will need a simplified market, with fewer drugs (purchased at higher volume) or standardised treatment courses.

They note that there might be secondary patents on some TB drugs even after the basic patents have expired that will need to resolved before generic companies can produce them.

They conclude that competitive large-scale generic manufacture could allow treatment of at least 10 times more MDR-TB cases while still operating within the procurement costs of current budgets. But such this would depend on overcoming patent barriers, competitive pricing, and scaling-up surveillance and case detection to increase demand for treatment.

References:

1. Gotham G 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.
2. Infodrive India.
   http://www.infodriveindia.com
3. STREAM
   http://www.ctu.mrc.ac.uk/our_research/research_areas/tuberculosis/studies/stream
4. Medicines Patent Pool. Press release. The Medicines Patent Pool expands mandate to hepatitis C and tuberculosis treatment. 6 November 2015.
   http://www.medicinespatentpool.org/the-medicines-patent-pool-expands-mandate-to-hepatitis-c-and-tuberculosis-treatment