TB Alliance Submission

International Development Committee: Humanitarian crises monitoring current situation and the immediate risks and threats

April 16, 2020

Introduction to TB Alliance

TB Alliance is a not-for-profit organization dedicated to the discovery, development and delivery of better, faster-acting and affordable tuberculosis drugs that are available to those who need them. We envision a world where no one dies of tuberculosis. Since our inception in 2000, TB Alliance has led the global search for and development of new TB regimens, catalysing the field and convening cross-sector partnerships to forge the progress that is urgently needed for better TB treatments. As a product development partnership (PDP), TB Alliance is uniquely positioned to leverage a global network of public and private partners to most efficiently advance TB drug development. A PDP builds partnerships between the public, private, academic, and philanthropic sectors to drive the development of new products for underserved markets and ensure effective pharmaceutical development is coupled with worldwide access, affordability and adoptability criteria. We combine the research and development expertise of our staff with the skills and resources of our partners to harness the most promising science wherever it may exist around the world. In 2019, TB Alliance became the first not-for-profit organization to develop and register an anti-TB drug.

Reason for Submission

TB Alliance implements large scale TB clinical trials around the world, testing novel drug regimens that have the potential to cure all forms of TB; additionally, our access program includes products that serve paediatric and drug resistant TB patients. The clinical trials we implement enrol TB and HIV patients as well as other vulnerable groups considered high-risk for serious or fatal outcomes from corona virus. The current crisis directly impacts our patients as well as broader target population and our ability to safeguard them against various increased risks. Below we outline these threats as well as challenges it poses on our staff and operations.

Our most immediate concern is based on our current knowledge of the corona virus, an airborne respiratory disease with a high mortality rate that will likely have a massive impact on populations and healthcare systems, especially in developing and emerging economies. Moreover, the new virus will disproportionately affect poor and vulnerable populations, who often live in overcrowded conditions and without safety nets. These circumstances will no doubt hinder if not totally prevent such vulnerable populations from social and physical distancing. An outbreak of COVID-19 is a ticking time bomb for these communities!

Over the years, global TB and HIV programs have made notable progress – the current pandemic, however, threatens these achievements. Socio-economic unrest fuelled by current and prolonged uncertainties as well as enormous pressures faced by healthcare systems may reverse or even worsen present global health realities and fragile states.

COVID-19 Impact on TB Alliance and Programs

In the immediate shock of the COVID-19 pandemic, TB Alliance has been working towards understanding the impact of Covid-19 across all aspects of our work. First and foremost, we are deeply concerned for the safety of our staff, those who work on our projects, and TB patients; this pandemic serves to markedly exacerbate the struggles and challenges that poor people and their communities constantly face – a lack of adequate diagnostics, preventatives and therapeutics, and perpetual social stigma. TB and TB-HIV co-infected patients, with their underlying pulmonary compromise, are both at extremely high-risk for being amongst the most severely affected by COVID-19 as well as more likely to suffer from the diversion of scarce health services to care for COVID-19 sufferers.   

 The challenges we are considering thus far from the impact of COVID-19 include:  

 Operations 

• As in all healthcare settings, the burden on our staff, contractors and consultants during these difficult times is enormous, both in workload and of course because of stress and anxiety about security.  We are continually evaluating how best to ensure the most effective and efficient deployment of personnel during this period of travel bans, both internationally and locally.  Similarly, we are employing all the technology solutions available to enhance communication and transfer of critical information.  We are fortunate in that we had already instituted an excellent IT infrastructure which is now invaluable.   

Patients and ongoing late stage trials 

• TB Alliance currently implements three large scale global clinical trials in several TB endemic countries in Africa, Asia, Europe and South America. Altogether these trials have enrolled over 600 TB patients. These patients represent both drug sensitive and drug resistant forms of TB but an overwhelming number of them include the most severe drug-resistant cases with historically and dramatically poor treatment outcomes and mortality.
• For enrolled patients, we now need to ensure continuity of treatment and follow-up visits so patients from these countries (e.g. South Africa, Tanzania, Moldova, Georgia, etc) can complete their treatment safely and be monitored and scientific data collected for future treatment. This phase of TB trials is lengthy.  We are now faced with multiple difficulties for patients to access health care systems in all countries in which the trial is being conducted. 
• Overcoming these will be difficult and costly and any operational shortfall both is a risk to patients as well as to the integrity of data that will allow proper evaluation of the outcomes. Delays and extensions would add to the costs of the trial and are a very likely possibility. 
• Overarching trial activities: There will be ripple effects emanating from the many partners and vendors we rely on to execute trials and the international nature of the trials which are impacted by logistical shutdowns. A prime example is the ability to ship patient samples needed for evaluation of drug resistance patterns and assessment of treatment effectiveness to central labs and ability to visit and monitor sites to ensure consistency in data collection. Continuation of community engagement, supply chain interruptions, retention of staff, curtailment of travel, more expensive medical supplies and equipment are but some of the challenges that have already surfaced and need to be managed.    

Early phase research and development

• Early stages of TB R&D include phase 1 and phase 2a studies as well as preclinical work and drug discovery.
• For phase 1 and phase 2a studies, TB Alliance had planned to start a number of these trials in 2020 but will invariably encounter delays as research and academic treatment centres around the world have all but closed for “non-essential” healthcare – and unfortunately some additional costs for us will continue to be incurred because of this. 
• Pre-clinical and manufacturing services we contract with globally have been closed or are experiencing extended delays.  

Science and global network  

• Scientific meetings and conferences, where we present data and have critical face to face meetings, have all been cancelled.  We now await the decisions for meetings scheduled for the fall, which may also be cancelled.  We will participate whenever possible in internet-based conferences and meetings.    

Market access/product introduction/Phase 4 trials 

• Planning and intensive work is ongoing to introduce the newly approved regimen for severe drug-resistant TB patients, called BPaL in short after the three drugs in the regimen, in priority countries over the coming months. We do not yet know the full impact the pandemic will have on a number of key actors and their ability to respond as planned to patient and country needs but we expect severe delays.  This includes dependencies on regulatory bodies, national TB programs, the WHO, Global Fund and the Global Drug Facility among many others. 

Funding

We are very concerned about the financial impact of this pandemic on us as an organization and our programs.  Above are multiple examples where we predict potential delays that inevitably mean additional costs or solutions to new problems that will invariably incur greater financial spend. With much bilateral funding coming from GDP-linked development budgets and the Gates Foundation’s dependency on its investments in stock markets, it is likely that there will be difficult choices to be made by donors that could impact ongoing and future research into new treatments against TB that are looking very promising. We have several upcoming grant renewals, DFID being one of them, and contingency plans such as budget-neutral one-year grant extensions would hopefully be considered. Of course, the current crisis does very strongly showcase both the need for public health focused research and product development in infectious disease management and global health security as well as the price of inaction. It is hard to say how these two will play out against each other.

In the coming days and weeks, we will continue to learn the full extent COVID-19 will have on our access programs and on our partners around the world.