What does new drug PaMZ mean for TB and HIV treatment?

Earlier this year, the TB Alliance announced that it was ready to start clinical trials for PaMZ, its new tuberculosis (TB) drug. PaMZ is a combination of three drugs, two of which have not been licensed for TB treatment before. If the trials are conclusive, it will only be the third new TB drug to be licensed in 60 years.

PaMZ’s development has been hailed as a breakthrough. It will be available for both drug-sensitive and some drug resistant TB patients (about a third of cases). In the case of the latter, it promises to reduce the treatment duration (from two years to six months) and its cost (from $2,000 to $100), simplify it (pills-only, no injection required) and improve cure rates.

PaMZ will also be compatible with anti-retrovirals (ARV) for treating HIV, offering a new solution for millions of co-infected HIV-TB patients. At least a third of the 35.3m people living with HIV are infected with TB and the disease is the leading cause of death among HIV-positive patients. To find out more about the potential value of the new drug, we asked four professionals what impact they see it having on their work.

Jan Gheuens, deputy director, drug development, TB programme, Bill & Melinda Gates Foundation

The TB Alliance has pioneered a new way of developing TB regimen by testing drugs in combination, which will accelerate the discovery of new treatments. They are aiming for a universal treatment plan. Drugs only have a certain number of years before resistance emerges – it’s a phenomenon we must take into account.

Donors are interested in TB because it is one of the big killers, but their decision-making process can be slow. We have provided supplementary funding for the clinical trials of PaMZ and are working with other donors to ensure it gets funded.

It is important that preparatory work about the adoption of PaMZ starts now. World Health Organisation (WHO) policy will be especially important as more countries become less donor-dependent for their TB programme and rely on WHO for guidance.

Dr Bern-Thomas Nyang’wa, TB specialist, Médecins Sans Frontières (MSF)

MSF has been treating drug-resistant TB patients for 15 years. It is our highest priority because it represents a major challenge for control now and in the future. In Uzbekistan, MSF now has more drug-resistant than drug-sensitive TB patients.

PaMZ is a very welcome development. The current regimen for drug-resistant patients is two years and it’s toxic. A third of our patients experience some form of hearing loss; some become completely deaf. Nausea and vomiting are common too. The treatment is expensive and, overall, not that effective.

We know that PaMZ will only work for around half of our drug-resistant TB patients so we’re looking at other drug combinations, although there are nowhere near enough new drugs in the pipeline.

We hope the TB Alliance will have agreements in place that allow competition between generic manufacturers: this is key to getting affordable drugs. Governments must also have clear registration processes that won’t hinder the adoption of the new programmes.

Dr David Moore, director of the TB centre at the London School of Hygiene and Tropical Medicine

The interaction between ARVs, HIV drugs and other drugs is very complex. At the moment, not all TB drugs can be given to patients on ARVs. Busy physicians in resource-constrained settings need the assurance that the drugs they’re prescribing are safe and that they don’t need to be concerned about interaction. If that’s what PaMZ can do for co-infected TB-HIV patients, it’ll be a huge development.

The fact that PaMZ is pill-only is another big advantage for drug-resistant patients, especially those who are also HIV-positive. They are often weaker physically and the injections can be very painful for them. Syringes must also be disposed of safely by health workers to avoid HIV infections.

A pill-only regimen will also greatly facilitate community-based TB treatment, something we have been working on in high burden countries to alleviate pressure on hospitals and to minimise the risk of infections.

Dr Surendra K Sharma, head of pulmonary, critical care and sleep medicine, All India Institute of Medical Sciences (Aiims)

Early research on PaMZ is very encouraging. For high-burden countries such as India, shortening treatment duration, especially for drug-resistant TB patients, will be a landmark because it will allow better patient adherence to the drug regimen.

We need good regulation in place for the distribution of PaMZ. It should not be available over-the-counter and should only be prescribed by qualified physicians and licensed through the national TB control programme. These new TB molecules are very precious and must be safeguarded. This is a serious concern for TB experts.

I would also like to see more work on vaccines. New drugs are very welcome but we haven’t been able to improve on the BCG vaccine developed in the 1920s – we really need to cross that benchmark.

Source: The Guardian