/ 5 July 2013

Anger over drug access in TB trial

Health activists in the United States and South Africa are crying foul about a drug that was tested in South Africa, Zambia, Botswana and Zimbabwe, despite it not being registered in any of those countries and therefore not available to patients other than those involved in the clinical trial. 

They also say that the drug, rifapentine, is far too expensive. Although there is no South African price for the drug, it is currently $1.60 a tablet in the United States, compared with five US cents a tablet for isoniazid, a drug currently used in tuberculosis regimens.

Although rifapentine has been used to treat selected American TB patients for years, it is largely unavailable outside of the US. This is partly owing to its high cost and partly as a result of little research having been done on the drug. Previous trials involving rifapentine have been disappointing, sporting high TB relapse rates and high rates of resistance in patients living with HIV.

But the results of a new study that were released earlier this year that stemmed from trials in different parts of Southern Africa showed that using rifapentine in conjunction with another up–and–coming TB drug, moxifloxacin, was just as effective as using isoniazid or rifampicin, the currently used drugs. The results were positive even in patients with HIV. 

Notably, patients involved in the rifapentine arm of the trial only had to take the drugs once weekly, as opposed to twice daily as in current regimens. 

"If you think about a bus driver [on TB medicine], he only has to come in once a week for directly observed therapy [with rifapentine]," says Amina Jindani of the St George's Medical School at the University of London, a lead researcher in the study. "That's a huge advantage. It has enormous potential."

Nathan Geffen of the Centre for Social Science Research at the University of Cape Town applauds the study's findings but says Sanofi–Aventis, the maker of the drug, is obliged to ensure that rifapentine is available in the countries where the trials took place. 

"In the Helsinki Declaration, which is suppose to guide the ethics of clinical trials, it says that the intervention must be available in the community in which it's tested once the trial's over," Geffen says. "Here that's just not the case."

The US Food and Drug Administration (FDA) first registered rifa–pentine in 1998 after the drug was tested in South Africa. 

"It's shameful that a significant amount of the research was conducted here and it wasn't registered here," says Marcus Low of the Treatment Action Campaign. 

He also says the high price for the drug keeps it out of reach of the majority of the world's patients. "At the current price there's absolutely no prospect of the drug being used." 

Low says that, although the rollout of rifapentine in South Africa is probably far off for programmatic reasons, "if it was affordable, there would be at least a discussion about whether we should change the guidelines. But that's just not an option."

Plans to register the drug in SA
Sanofi–Aventis told the Mail & Guardian that it is planning to register the drug in South Africa and hopes that it will come to market by 2015. 

Prudence Mahapa, head of communications at Sanofi–Aventis South Africa, says: "[The] Sanofi access to medicines policy is to have affordable medicines for those who need it and rifapentine will follow this rule when available in South Africa and in other countries." 

Jindani says that, as the use of rifapentine rises, the price of the drug is expected to fall. 

Erica Lessem of the New York–based Treatment Action Group says that a combination drug that includes both rifapentine and isoniazid – used for preventing latent TB infection from turning into active disease – is likely to be approved by the FDA in early 2014.

Mahapa says that Sanofi–Aventis is being unfairly targeted as it did not conduct the study. 

"Sanofi may not technically be the sponsor but donates the study drug and has staff sitting on the protocol team," says Lessem. "It's hypocritical to invest so much on the research side and then thwart access with drug prices. Even in the US … rifapentine is too expensive to be routinely accessible for programmes."

But Jindani warns that the world may not be ready for widespread rifapentine use yet, noting that cost and registration are only part of the problem. Rifapentine is better absorbed if it is taken with food and, although meals were given during the clinical trial, this can't be assured in the real world. Jindani also says that, because of its high price, it's essential to see whether isoniazid can be used instead of moxifloxacin during the first two months of treatment and achieve similar results. 

A trial is currently being conducted to establish whether a TB drug regimen containing moxifloxacin could reduce treatment from six months to four months, significantly easing the burden on drug–sensitive TB patients. There are 48 clinical trial sites currently testing the regimen, including several in South Africa, and results are expected at the end of the year. While Bayer has committed to reducing the price of moxifloxacin for TB use, Jindani says that even if the price were halved, it could still be prohibitively expensive. The TB Alliance, which is working with Bayer on the so–called REMox trial, says it is committed to ensuring that all the drugs it works on are affordable and accessible. 

Some of Jindani's fellow researchers at St George's are hoping to test the rifapentine regimen without these two factors but are awaiting funding. Until that happens, Jindani says, "it's too early for general availability for the drug".

Some TB drug prices are dropping. Last week, the Global Fund to Fight Aids, TB and Malaria announced that it would begin buying a generic  of the antibiotic linezolid, originally produced by the drug company Pfizer. 

Although linezolid has been shown to be effective in treating drug–resistant TB, the Pfizer product is expensive: in South Africa, it costs R282 a pill in the public sector and R593 a pill in the private sector. The Global Fund can now buy a version from the Indian company Hetero for only R25 a tablet. It is hoped that a nod to the Hetero product from the global fund may encourage other funding organisations and national departments of health to begin buying the cheaper generic as well.