By: Alanna Shaikh
Right now, two drugs are approved for Chagas disease, benznidazole and nifurtimox. Count them. 1. 2. Doesn’t exactly insure confidence, does it? Also, as an added bonus, they’re 30 years old, which means that there is plenty of resistance to the drugs. They only work in 60-85% of adults, although, thankfully, they do better on children. It’s clear, though, that in terms of Chagas treatment, there is really nowhere to go but up.
That’s why this press release is such good news. “Merck today announced plans to initiate a Phase II investigational proof-of-concept clinical study to evaluate its oral antifungal agent posaconazole for the treatment of chronic Chagas disease.” (Don’t worry, I’ll translate.)
After spending some quality time with Wikipedia and google. I can tell you that a proof of concept study is what they do to determine that a drug can work. It’s the small, brief, study with carefully selected participants that comes before a bigger clinical trial. So, if posaconazole turns out to be effective in this small study, it will go on to broader testing.
The proposed study will be randomized and placebo controlled. It will test the effectiveness of 60 days of posaconazole treatment in 160 adults in South America.* It will follow the participants for 360 days. They’ll test the participants’ blood for the presence of the parasite that causes Chagas disease.
images.com/corbis
If posaconazole is effective in the proof on concept study, it will go on to full trials. That will mean more participants in more locations, and possibly longer periods of time. However, posaconazole is already on the market for other diseases. It is being used in the US to treat Aspergillus and Candida infections in immunocompromised patients 13 years and older. That means we already have safety data on the drug. We don’t have to do a million studies to see if it has horrible side effects. We just have to find out if it really works for Chagas disease.
So, maybe we’re not too far away from a third drug for Chagas disease. That’s a 50% increase in available treatments. Everybody cross their fingers and knock on wood.
It also makes me wonder – how many existing drugs might work on other NTDs? If there is a drug that works for Chagas already in use, what else might be out there? Are we going to find out that Tamiflu works on encephalitis? Prilosec for elephantiasis? Triclosan for trachoma?
Probably we’re not going to find an NTD miracle cure in the bathroom cabinet. But I am awfully glad for the reminder that pharmaceutical companies are still hard at work seeking treatments, even for neglected tropical diseases.
*This is a great example of drug research done right in the developing world. They’re testing the drug in South America, which is also where the drug will have the most impact. That’s not medical exploitation. It’s responsible testing and responsible medicine.
Alanna Shaikh is an expert in health consulting, writing about global health for UN Dispatch and about international relief and development at Blood & Milk. She also serves as a frequently contributing blogger to ‘End the Neglect.’
Great find here, Alanna. Chronic T. cruzi infections are notoriously difficult (if not impossible) to treat, so the fact that this trial aims at chronic phase Chagas disease is very welcome news indeed!
One precaution: since there presently is no reliable test of cure for Chagas disease, there may be trouble with interpretation of results of the trial. I don’t know enough about T. cruzi to say if it only exists in the blood (where the levels are being tested as the main measured outcome of the trial), but it may be that reservoirs exist elsewhere in the body, where the bug can hide out, waiting to re-infect. It may be difficult, therefore, to know whether the drug will make a true difference to patients, especially since signs and symptoms can take decades to develop. This underlines the urgent need for the development of a test of cure before we can really move forward on Chagas disease drug development.
On the other hand, a bonus here is the drug is available in an oral formulation, meaning that delivery will be practical in the very poor, remote, rural areas where Chagas disease is endemic. Some anti-fungals and anti-kinetoplastids (related to the Chagas disease-causing organism) require an IV injection for several weeks!