IMI’s Pre-DICT TB Consortium is a major step towards eradicating the disease
24.03.15
Dr Gerry Davies, Reader in Infection Pharmacology at the Institutes of Global Health & Translational Medicine, University of Liverpool, UK, talks to EFPIA about the value and contribution of the Pre-DICT TB Consortium, of which is currently the academic coordinator.
The lack of interest in this field of drug development can be explained. “Partly this is because it is not a profit area, but the real issue is that it was perceived to have been resolved by the end of the 1970s,” explains Davies. In a sense, before the emergence of the HIV epidemic, this may have been more or less an acceptable scenario, but that is no longer the case.
There is an urgent need for science in the TB field to progress, says Davies. For example, the duration of treatment, at some six months, is unacceptably long, leading to a gradual erosion of patient adherence. “The flip side of that is that when people don’t take their drugs properly or don’t get the right drugs from their physicians, they develop resistance,” Davies explains. In fact, there are some half a million people worldwide, who now needed treatment for multidrug resistant TB.
“The scientific community, and shortly after that the pharmaceutical community, woke up to that fact about 10 years ago,” Davies says. They began to understand the problems facing drug development in TB. There was, for example, a lack of preclinical models that were well validated and clinical trials methodology had not been developed very extensively.
“So really what we have set out to do within the framework of Pre-DICT TB is to evaluate the whole range of preclinical models that currently exist in TB,” says Davies. They are being evaluated over a defined range of drugs from 10 different classes.
“We have set it up in such a way that these are all drugs that have been used in combinations that have been used in clinical trials,” Davies explains. Specifically they have all either been in, or will shortly go into, Phase III trials. From here, researchers can evaluate the potential of the pre-clinical models.
The project has been divided into two phases. During the first two years of the Pre-DICT TB, researches looked at “historical” drugs, those, that currently are in use. Of course, researchers have full knowledge of the original clinical trials involving these drugs, as their results were published some thirty years ago.
Over the next two years, the project will focus on newer drugs, including Jannsen’s Bedaquiline (TMC-207). Bayer’s Avelox (moxifloxacin) is also a subject for the project. While not new in itself, its use in TB is novel.
Otsuka, meanwhile, also has an interesting product out, in Deltyba (delamanid).
Some of the newer drugs have been licensed to treat MDR TB, but would they be useful as first-line therapies? Moreover, if they could be used in first line, would they be able to reduce the current treatment duration of 6 months?
The contribution of IMI has been to facilitate a cross-disciplinary/cross-sectoral approach by offering funding to bring the various interested parties together. “Hopefully, what we will have at the end of the five years of the project is a much more complete picture of what the place of all these different models might be along the development pathway and some new proposals for how to define that pathway and make it more effective,” Davies says.
The project is now approaching the end of its third year and the interim review from IMI has been extremely positive. “We are at the stage of the project where we are taking stock and thinking about what things we might be able to do better and whether we might want to change the emphasis of some of the work,” Davies notes.
The industrial aspect of the project has been buoyed by the presence of the Pre-DICT TB consortium’s coordinator, GSK. “ So what we are undertaking internally is a review of the reliability in the performance of different models and at the same time starting to think more clearly about what precise contribution they make to the development pathway,” Davies says.
So what might be achieved from an industrial perspective at the end of the project is the creation of a refined set of tools and a more useful drug development pathway that will eventually enable manufacturers to produce therapies at lower cost and faster.
It is debatable as to whether such a project could have had the same, high-level impact and success outside of the IMI’s public-private partnership framework.
“IMI is all about pre-competitive research, so industry partners would need to take best practice and the most advanced science from the public sector to be able to incorporate that into their drug development programmes,” explains Davies.
At the same time, in the TB field the academic community remains relatively small and has limited research capabilities in comparison with other potentially profitable areas, such as cardiovascular disease or oncology.
So the synergy between the two sectors is what has brought about the new approach and promise for TB sufferers. “From the investment that IMI has made and that EFPIA has put into this, I hope that what they will get out of it will be a genuine means of accelerating drug development in TB because it is desperately needed,” says Davies.
Moreover, he adds that the companies involved in the Pre-DICT TB consortium have made a tremendous commitment to undertake TB drug development in what is for them a not-for-profit area.
So this appears to be the correct path to take, but the World Health Organization is aiming to eradicate TB by 2035 and a question remains as to whether this is a real possibility.
“Better diagnosis, vaccines and treatment would help, but what would really tip the balance would be treatment of what we call ‘latent infection’,” Davies suggests. This refers to people who present as being healthy, but are in fact infected with TB.
So there is some way to go before academia, governments, industry and other healthcare stakeholders may confirm that they are on track to meet the WHO goal. In the meantime, though, IMI’s Pre-DICT TB Consortium is a significant step in the right direction.