Breath of Hope: TB in Africa - Pharmaceutical Executive


Breath of Hope: TB in Africa
For the first time in decades, pharma has tuberculosis drugs in the pipeline. But it will take more than new pills to solve the problem. Executive Editor Joanna Breitstein reports from East Africa.

Pharmaceutical Executive

Given the resources needed to ensure patient safety and compliance, administration of these new second-line drugs was erratic, says Jaramillo. In response, WHO created the Green Light Committee (GLC), a subgroup of the Working Group on DOTS-Plus for MDR-TB, to reduce the price, and promote rational use of MDR-TB drugs. GLC obtains price concessions on drugs, but to take advantage of them, organizations must apply to GLC for a technical review to ensure their project makes rational, thoughtful use of second-line therapies. Based on the numbers, GLC has largely done its job: Since 2000, it has reduced the cost of second-line treatments to $1 a dose and now supplies drugs to 37 projects, says Jaramillo.

WHO's "Global Plan to Stop TB, 2000-05" offered a map of pilot projects to demonstrate that it was possible to treat MDR-TB in resource-limited settings. The second Global Plan offers scale-up plans: Only 10,000 MDR-TB patients were treated in the last five years, the second plan aims to treat almost 900,000.

That's a huge increase, and supply is already problematic for second-line therapies. Since 2003, Eli Lilly has sought to increase production of capreomycin and cycloserine by expanding its facilities and signing technology transfer agreements with companies in India, South Africa, and China. But even when completed, these initiatives are unlikely to solve the problem of very long lead times.

"Companies don't want to take the chance of producing expensive therapies that might not be consumed," says Kathryn Kempton, director of procurement at Partners in Health, an NGO focused on TB. "They often don't start production until we place an order—creating 8-, 12-, or even 24-week lead times—which is challenging for projects. If WHO or others could invest in an existing supply or create more transparency about how many patients there are in the market, that would help increase the production, and make our lives a lot easier."

WHO is investigating the feasibility of maintaining a buffer stock of MDR-TB drugs, which would allow programs to ramp up faster and reduce waiting lists, says Jaramillo. But the world is still facing a dearth of manufacturers that can produce MDR-TB drugs that meet the high standards of WHO's prequalification list.

Looking Forward

After years of neglect, TB is finally starting to receive the attention it deserves. "This latest round of the Global Fund, round five, saw TB get its most significant approvals to date," says Robert Matiru, manager of WHO's Global Drug Facility. "That was a dramatic increase in dollars earmarked for TB compared with the previous four rounds of funds combined."

Novartis also just donated 500,000 TB treatments in fixed-dose combination (FDC) for use over the next five years in Sri Lanka and Tanzania. These FDCs reduce the pill burden from eight to 11 pills per day to three to four. "That's the first collaborative arrangement of that kind that we have established," says Matiru. "In the future, we want more of those agreements with companies."

Better science is also on the way: Young noted that his multi-national research team for the Gates Grand Challenge was zeroing in on five targets that may be instrumental in latent infection and shortening TB treatment times, while NIH scientists have discovered the target acted upon by PA-824, a drug candidate purchased by the TB Alliance from Chiron. Meanwhile, OPC-67683, a compound owned by Otsuka, was found to be "far more potent than any of the existing drugs that we used for comparison," says Vince Lawlor, from the company's TB Drug Project.

More companies have entered the TB research arena, including Sanofi-Aventis and Johnson & Johnson. However, the TB Alliance says it is still not getting the kind of critical participation from other players, like biotechs, which can offer important knowledge in terms of biomarkers and surrogate markers.

New TB drugs haven't come to the market for 40 years, and perhaps the greatest challenge is the lack of TB-specific regulatory guidelines for drug development, including fast-track approval guidelines. The TB Alliance is working to bring that issue to the forefront. It hosted a meeting in December that included FDA and addressed issues such as the design of clinical programs for novel combinations of therapies.


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