Graeme Bilbe, Research & Development Director, DNDi
What would you say were the three main achievements in DNDi’s R&D portfolio in 2016?
The first thing that comes to mind is sleeping sickness. We’ve reached an important milestone for DNDi with fexinidazole as it is our first new chemical entity (NCE) to get through Phase II/III clinical trials successfully. Not only that, but we only lost two out of a total of 390 patients to follow up. This is truly an incredible result in the real-life conditions of running clinical trials in the DRC, so kudos to the clinical teams. And behind fexinidazole, we have another oral drug, SCYX-7158, in Phase II/III trials, so there is lots of promise.
Second, I’d say the advances in our leishmaniasis pipeline. We now have two pre-clinical candidates, and two other series in advanced lead optimization, plus our partners have signaled up to an additional four compounds close to pre-clinical candidate development. Together with our partners, we have NCEs representing six new classes of potential drug with unprecedented efficacy against both visceral and cutaneous leishmaniasis in animal models. So overall, the pipeline is looking very healthy and could transform the treatment landscape for leishmaniasis.
And in three, I’d pick the great strides made by our team working on hepatitis C. In less than a year, we’ve gone from signing a Memorandum of Understanding with the Egyptian drug manufacturer Pharco Pharmaceuticals, building a great collaboration with Malaysian and Thai governments, and now we have about 190 patients enrolled in our Phase II/III trial.
Have our R&D strategies evolved much since DNDi was created?
From the start, we took a three-pronged strategy: short- medium- and long-term. Short-term means improving access to existing medicines by completing registration and extending the geographical reach of existing treatments. In the medium-term, the focus was on therapeutic switching, combining and reformulating existing treatments to improve them so that they are better adapted to field conditions and patient needs. ASAQ for malaria, NECT for sleeping sickness, and SSG&PM for visceral leishmaniasis are some of the results of this short- and medium-term strategy.
For some of these, the treatments we developed are still be suboptimal, in that R&D needs still remain acute. But without question they have saved neglected patients’ lives. The impact of NECT for example is pretty telling: the number of HAT cases has decreased from hundreds of thousands to tens of thousands, and there are now only 3,000 left in those areas that we have been able to access.
For other disease areas, progress has been slower. Our work on paediatric benznidazole has taught us a huge amount about Chagas disease. We have trail-blazed the use of PCR as a readout for parasitaemia and have hope for a future proof of cure. Using PCR, we discovered that benznidazole is quite effective, so we are now working on alternative regimens and combinations to increase its tolerability.
As for the long-term: DNDi’s strategy is to invest in drug discovery to produce new fit-for-purpose treatments with improved efficacy and tolerability. These efforts are bearing fruit – we currently have 15 NCEs in our pipeline for all kinetoplastid diseases, mycetoma and hepatitis C.
Looking ahead, what future challenges do you foresee for DNDi within the broader R&D landscape?
The main challenge for DNDi’s R&D teams will always be to deliver new treatments. R&D for infectious diseases is subject to high attrition: we estimate that for every 1,000 hits only one will become a registered drug. Our way of mitigating that has been to increase substantially our number of clinical research projects and develop an integrated strategy for drug discovery, including risk management strategies.
But we have enormous faith in the DNDi model. So much so that a few years ago we decided to evaluate regularly any new potential disease to add to the DNDi portfolio and determine whether DNDi can have an impact and should enter the field. We’re expecting this to result in investment in new disease areas or fields of research and hence an increased number of partners – one immediate example is antimicrobial resistance, where we established the Global Antibiotic Research and Development Partnership (GARDP) in collaboration with WHO last year.
Another challenge will be how to continue to raise awareness for diseases that remain more than neglected, such as mycetoma, which are ignored in the shadow of deadly outbreaks of viral diseases like Ebola. And access to treatments will definitely remain a priority action. We still need governments to acknowledge that some diseases such as Chagas disease are a public health issue in their countries, and for all stakeholders to take responsibility and provide support to ensure patients aren’t neglected. Securing access to affordable hepatitis C regimens will also be a critical challenge.
It’s important to remember DNDi was only ever meant to be part of the solution for neglected patients. We’ve advocated for governments to create a framework for all R&D actors to work within, that is sustainable, focused on public health priorities and patients’ needs, and ensures that the results of R&D are affordable and available. And while there’s no shortage of expert reports that recommend that a framework along these lines be created, we’re not yet seeing enough government action that will address all areas of public health importance. Going forward, that is the challenge at its most fundamental.
Graeme Bilbe, Research & Development Director, DNDi