On occasion of World TB Day, we talk to EU-PEARL specialists on Tuberculosis (TB) Daniella Maria Cirillo and Riccardo Alagna to learn about where we are in the fight against TB, what is needed to meet UN targets for 2030 and how this IMI project is contributing to it.
- Today is World TB day. Why do we need to mark a day in the calendar to raise awareness about TB?
TB Day calls all stakeholders involved in the fight against tuberculosis to come together to raise awareness, to celebrate success, and to remind to the world that TB is still the N°1 killer among the infectious diseases. TB is a curable disease in the high majority of cases, however, delay in the diagnosis and non proper treatment contribute to the severity and mortality of the disease as well as the risk of transmission.
- Where are we now in terms of eradicating the infection and disease globally?
Despite TB elimination is on the right track, numbers are slowly declining to meet the 2030 Sustainable Development Goals. The target set by the United Nations is to reduce incidence by 80% and mortality by 90% from 2015 levels. In 2019, TB caused an estimated 1.4 million deaths. About 10 million (range, 8.9 –11 million) people developed the disease worldwide.
Incidence has fallen by 9% (target being 20%) and mortality by 14% (target was set at 25%). Drug-resistant TB (DR-TB) continues to be a public health threat. About 3% of cases registered in 2019 and 18% of previous cases were multi drug-resistant TB/rifampicin-resistant (MDR/RR-TB). There is still huge variability amongst countries and progress to reach the global targets is lagging behind.
- From a scientific standpoint, what is holding us back?
The funding gap in TB research and development (R&D) is estimated at more than 1 billion every year. Covid-19 has taught us that when both political commitment and sufficient financial support are available, the scientific community can work together to do some pretty amazing things.
TB field lacks simple and rapid tests, able to accurately detect TB and drug resistance as well as a better test to rule out TB. New diagnostic tools are currently being developed and evaluated. TB treatments rely on a combination of multiple drugs that need to be taken for several months. These result in a global cure rate of 85-90% for Drug-susceptible-TB, 55% for multidrug-resistant TB (MDR-TB)and 34% for extensively drug-resistant TB (XDR-TB).
Development and trial validation of three or four new drug regimens, requires over two decades under the current “modus operandi”. Identification of improved drug regimens and novel antibiotics, as well as innovative strategies combining modulation of the host responses with proper antibiotic treatment are needed.
The only vaccine available is inadequate in halting the global TB epidemic. TB vaccine development is difficult and slow. Successful licensure and deployment of an effective tuberculosis vaccine still face many challenges. Several TB vaccines are in the advanced stages of clinical development. If we want to achieve results, we will have to find necessary resources and explore innovative avenues. The TB epidemic cannot end with the tools available today.
- How can EU-PEARL contribute to eradicate TB?
Shorter, simpler regimens are urgently needed for the treatment of TB. The current treatment drug sensitive TB has not changed for the past 40 years and it is not adequate considering that around 10% of patients are forced to stop treatment prematurely. Exciting progress has been made over the last decades, and the use of the novel or repurposed drugs holds considerable promise for shortening MDR- and XDR-TB therapy and improving patient outcomes. However, the most important challenge in TB drug development is our limitation in identifying optimal regimens early and efficiently.
Over the past several years, TB drug development has enjoyed a renaissance and easing the clinical trial process will encourage industries and sponsors to stay engaged in this relatively unattractive market.
The Integrated Research Platform (IRP) EU-PEARL is developing to address the complexity, length, and expense of conducting TB clinical trials will hopefully increase the number of clinical trials and make TB drug development more efficient. In addition, by addressing factors contributing to long duration of TB drug clinical development, the project may potentially help reduce the impact cost of future clinical trials.
- What progress has been made so far within the project to advance in this direction?
EU-PEARL’s TB Work Package is working to introduce a paradigm shift in the way TB drug development is conducted. We are working hard to conduct a systematic review to identify potential biomarkers that can speed up the clinical trials by detecting outcomes earlier. In parallel, we are developing an adaptive trial design that can accelerate Phase II and III trials and improve our ability to select regimens for further investigation.
The success of any clinical trial is dependent on the preparedness of the trial sites and their adherence to the protocol. With this in mind we are developing a handbook that will help to assess site readiness and therefore ensure successful implementation of platform trials. But EU-PEARL does not work in silos and our workstream is continuously working to identify synergies with current and future TB clinical trial initiatives.
Daniela Maria Cirillo, MD, PhD, WP5 Leader at EU- PEARL is Head of Emerging Bacterial Pathogens Unit at the Università Vita-Salute San Raffaele and Director of WHO Collaborating Centre ITA-98/, TB Supranational Reference Laboratory.
Riccardo Alagna, MSc, MPH, WP5 Project Manager at EU-PEARL is a researcher at the Emerging Bacterial Pathogens Unit at the Università Vita-Salute San Raffaele; and Coordinator of WHO Collaborating Centre ITA-98/TB Supranational Reference Laboratory.