Access To Medicines

Better DR-TB medicines desperately needed

24 March 2014 – World TB Day

Currently available medicines for drug-resistant tuberculosis (DR-TB) require 18 to 24 months of treatment. This consists of a regimen of anything from 4 to more than 20 different pills daily, plus supplements and regular injections. These medicines can have serious side effects, including hearing loss and liver failure. According to the WHO Global TB Report 2013, South Africa counted close to 16,000 MDR-TB cases in 2012 of which only 42% were started on treatment. Of those that start treatment less than half are currently being cured.

The treatment success rate for MDR-TB in South Africa was 40% in 2010, according to a presentation presented by Dr Norbert Ndjeka at a DR-TB Strategic Planning Meeting in October 2013, Director Drug-Resistant TB, TB and HIV at the National Department of Health, while the mortality rate was close to 20%. According to the same presentation, the success rate in certain provinces was as low as 21.5%. For XDR patients, the situation is even grimmer with a success rate of less than 20% and a mortality rate of almost 50% in 2010.

While many factors contribute to the poor prognosis for MDR and XDR TB patients, the lack of better medicines stands out. To improve this situation we need medicines that can cure DR-TB in a shorter period of time and that have fewer side effects.

There are two broad obstacles to solving this problem:

Firstly, too few new medicines for tuberculosis are being developed.

This is in part because TB is mainly, though not exclusively, a disease that affects poor people. As a result, pharmaceutical companies have comparatively little economic incentive to invest in developing new TB medicines. Despite a few promising TB medicines nevertheless currently being in development, the future for TB drug development looks bleak. Earlier this year the pharmaceutical company AstraZeneca announced that it would stop all early-stage research into neglected tropical diseases, TB and Malaria. In 2012 the pharmaceutical company Pfizer closed its TB drug development program by closing its anti-infectives research division.

In the same year, funding for tuberculosis research and development (TB R&D) dropped by US$30.4 million compared to 2011, leaving a gap of $1.39 billion to reach the recommended $2 billion annual investment, according to the 2013 Report on Tuberculosis Research Funding Trends, 2005–2012 by the Treatment Action Group (TAG)[1]. Pharmaceutical companies reduced their investment in research and development for TB with 22%, contributing only 18% of the total TB R&D in 2012. This drop in private sector spending has placed even more pressure on the public sector which is already suffering from budgetary cuts due to the global recession.

The same report notes that the BRICS countries, including South Africa, are “sorely underrepresented among the top 30 donors”, despite accounting for 40% of the world’s notified TB cases and 60% of its estimated MDR-TB cases. A study by David Walwyn showed that in 2010 South Africa spent a mere 0.02% of its GERD (Gross Expenditure on Research and Development) on research and development for TB.  GERD includes expenditure on research and development by business enterprises, higher education institutions, as well as government and private non-profit organisations. The same study, however, also notes that while the Department of Health set a target to spend 2% of its health budget on R&D in its 2001 Health Research Policy, it only spent a meagre 0.37% in 2011/2012. [2]

It is essential that governments, particularly governments of high TB burden countries, must spend more on TB research. This must include spending on basic research through grants, but may also have to include innovative funding mechanisms like innovation inducement prizes or advanced market commitments.

Secondly, we need to do more to ensure that existing and experimental TB medicines are used optimally. This is difficult and requires very careful consideration. However, a few broad points seem clear.

We need more high quality randomized controlled clinical trials to understand the safety and effectiveness of existing and experimental medicines. Without such trials we risk using existing medicines sub-optimally and exposing patients to unnecessary side effects. Medicines regulators, the World Health Organization, national treatment programmes and pharmaceutical companies all have a role to play in ensuring we build up a better evidence base for the medicines we use to treat tuberculosis. We need the WHO and medicines regulators to show leadership and to insist on more and better trials. We need governments and funding agencies to fund the important trials. We need pharmaceutical companies to make their medicines available for these trials.

However, the optimal use of existing and experimental medicines also requires that access to these drugs must be facilitated. This can happen through compassionate use programmes where patients with no other recourse are given medicines that have not yet been approved. In this regard, more people in South Africa must be given compassionate access to the experimental DR-TB medicine Bedaquiline. Similarly, the pharmaceutical company Otsuka must urgently expand their very limited compassionate use programme for their DR-TB medicine Delamanid.

Unfortunately, pricing is also limiting access to DR-TB medicines.

Linezolid, one of the only effective treatments for drug resistant TB, is priced at R676 per pill in South Africa, whilst a generic version of the same drug is available at only R25 per pill in India. The drug is patented by Pfizer in South Africa. This patent blocks quality-assured generic versions from being marketed in South Africa and driving down the price. With 16,000 confirmed cases of MDR-TB and a cure-rate of less than 50%, the high price of Linezolid means many patients who need it can’t access it. MSF estimates that 300 patients in their Khayelitsha treatment programme requires linezolid, but due to the high price MSF doctors are in the very difficult position of having to decide which 22 patients they can give the drug to.

The South African government urgently needs to fix its patent laws to allow for better access to this and other life-saving anti-TB medication. A more workable compulsory license system would for example have allowed MSF to apply for a compulsory license that would allow the import of much cheaper linezolid generics from India. Even if such a license was never granted, the mere threat of such a license would have forced Pfizer to price linezolid more reasonably.

 Note: TAC is currently conducting investigations and research into TB in correctional facilities and the treatment of drug-resistant TB in the public health system. We will report on both these investigations in the coming months.

[1] Frick M and Jimenez-Levi Eleonora, 2013 Report on Tuberculosis Research Funding Trends,2005–2012. Treatment Action Group and Stop TB Partnership.

[2] David R Walwyn, Determining quantitative targets for public funding of tuberculosis research and development, Health Research Policy and Systems 2013.