Moxifloxacin, already approved to treat severe respiratory infections, has entered the final phase of clinical trials, offering hope that a shorter course, four-drug combination could be available to cure tuberculosis (TB) by 2011.

Meanwhile, a new drug, PA-824, is entering a Phase II trial, the Global Alliance for TB Drug Development (TB Alliance) announced in Cape Town yesterday (Thursday).

With multi-drug resistant (MDR) TB on the increase worldwide, a new drug is urgently needed.

The Phase III clinical trial of moxifloxacin will involve 2 400 TB patients in Cape Town and other African countries.

The trial is designed to test whether a four-drug combination regimen including moxifloxacin, can reduce TB treatment time from six months to four months.

Early studies have suggested that combination therapy, where the moxifloxacin replaces one of the current standard TB drugs, ethambutol or isoniazid, has the potential to shorten the treatment period for TB with better outcomes. Researchers will also test that the drug combinations are compatible with antiretrovirals.

Some doctors (not in South Africa) are already using moxifloxacin off-label to treat MDR-TB.

PA-824 is the first novel TB drug candidate developed by a not-for-profit organisation to reach clinical trials, and is now in its first test in TB patients in Cape Town.

Researchers said that PA-824 shows promise for the treatment of drug-susceptible and drug-resistant TB, and may contribute to treatment shortening when in an effective combination regimen.

PA 824 is undergoing a Phase IIa study in patients to test of its short-term potency as a single drug. Patients enrolled at two sites in Cape Town receive either PA-824 or the standard, four-drug TB treatment for 14 days.

Many are keeping their fingers crossed that PA-824 and moxifloxacin prove to be successful as it will be a massive boost for the TB Alliance’€™s efforts to address the lack of new drugs for TB.

TB mostly affects poor people providing very little incentive for drug companies to invest large amounts of money in finding new drugs.

The TB Alliance, a not-for-profit body formed in 2000 between TB stakeholders, including pharmaceutical companies, has been working to accelerate the discovery and development of new drugs to fight TB.

Bayer, the drug manufacturer for moxifloxacin, and the TB Alliance have committed to making the drug affordable and available for TB patients where it is needed most, especially in developing regions.

The Food and Drug Administration (FDA) has granted PA-824 fast track designation, which is designed to expedite the application and review process for products that have the potential to address a serious or life-threatening condition.

The FDA and European Union have approved an ‘€œorphan’€ drug designation for PA-824, which will reduce the cost of developing and registering the drug.

The TB Alliance has also signed an agreement with Novartis ensuring that the technology to manufacture PA-824 will be made available royalty-free in endemic countries.

Dr Mel Spigelman, Director for Research and Development at the TB Alliance said it was critical for the treatment duration to be shortened, for there to be no interactions with ARVs and for the drugs to address drug resistance.

Outgoing CEO of the TB Alliance Dr Maria Freire warned that based on its current financials the organisation would run out of money by the end of 2009.

The Bill and Melinda Gates Foundation fund almost 70 percent of the TB Alliance. ‘€“ Health-e News Service