Ebola Vaccines and Antivirals: What Lies Ahead?
December 30, 2014
A pivotal moment
On Tuesday, December 16, the CSIS Global Health Policy Center hosted a discussion centered on current efforts to develop safe, effective, and affordable Ebola vaccines. There was also a brief discussion of new therapies.
Panelists included Dr. Anthony Fauci, Director of the National Institute of Allergy and Infectious Disease (NIAID); Dr. Julie Gerberding, President of Merck Vaccines; Mr. Rohit Malpani, Director of Policy and Analysis at the Medecins Sans Frontieres (MSF) Access Campaign; Dr. Moncef Slaoui, Chairman of GSK Vaccines and member of the GSK Board of Directors; and Dr. Johan Van Hoof, head of Infectious Diseases and Vaccines at Janssen Research & Development, of the Johnson and Johnson family of pharmaceutical companies. Dr. J. Stephen Morrison, Director of the CSIS Global Health Policy Center, offered opening remarks and moderated the discussion.
The session grew out of a shared sense that a pivotal moment has arrived. In the final quarter of 2014, rapidly accelerating efforts to develop Ebola vaccines have stirred excitement and raised expectations, tempered by continued uncertainty about the safety and efficacy of vaccine candidates. 2015 is likely to witness multiple, ambitious field trials in West Africa and elsewhere, in the midst of formidable challenges and continued debate.
The afternoon’s conversation surfaced three compelling themes:
- The emergence of promising multi-sector partnerships;
- The need for a strategic approach to preparedness, by industry and governments, to avoid the failure seen in 2014; and
- The need for a clear-eyed, smart approach to field trials and possible future dissemination of vaccines in West Africa.
Dynamic partnerships are emerging.
Something unusual is afoot. The Ebola crisis has generated a “high sense of urgency” that has in turn stirred dynamic collaborations across industry, governments, NGOs, international organizations, and foundations. These partnerships are exceptional in the speed with which they are evolving and the flexibility they have evinced. Ample resources are flowing towards the Ebola R&D response from multiple directions: in this instance, luckily, money does not appear to be the major problem. A recent promising step is that following its mid-December board meeting, Gavi, the Vaccine Alliance, has committed to play a critical financing and coordinating role, should a WHO-approved vaccine become available.
An unusual consensus has emerged. There is a shared recognition of the high risks of delay and inaction, a balanced optimism and realism about what may be possible on an expedited basis, and a common determination to think ahead beyond the immediate situation to address future basic health infrastructure requirements and prepare for second generation vaccines. There is hope that new vaccines could play a vital role in ending the outbreak and responding to inevitable future episodes.
Competitors such as Merck, GSK, and Johnson & Johnson are now actively partnering to develop and evaluate a number of vaccines and therapeutics. According to Dr. Van Hoof, synergies among the various stakeholders have helped to compress R&D timelines from years into months, with some very promising results. Plans have moved ahead by industry to have in place expanded manufacturing capacities in 2015 that can bring vaccine production to scale, if and when that becomes possible.
According to Dr. Fauci, there are currently five Ebola vaccines in the pipeline: two currently in Phase I testing, two to be tested in 2015, and one with a testing date yet to be determined. The most advanced candidates, anticipated to be evaluated in field trials in early 2015, have stemmed from collaborations between industry and US agencies, including the NIAID/GSK Ebola vaccine, and VSV-EBOV from NIAID, Merck, and the Department of Defense.
The Ebola crisis has stirred considerable soul-searching.
The abrupt shift of resources toward Ebola R&D is itself proof of how ill-prepared governments, industry and others indeed were as the Ebola crisis appeared in 2014. Echoing the comments of other panelists, Dr. Gerberding described the recent outbreak as a “predictable surprise” and pressed further: “How many outbreaks do we need to experience, before we have a sustained response?” Dr. Slaoui of GSK emphasized that Ebola is the fourth major bio-threat in recent memory; in its wake, many in industry are asking themselves how to prepare more strategically. Companies have in late 2014 have sprung forward with major Ebola commitments, but these are episodic, unplanned add-ons that stress other important global commitments.
What is needed to create a more strategic approach to preparedness? This is hardly a simple matter. The field is fragmented by multiple interests, and there is no strong forum for bringing coherence and informed, forward-looking planning. Threats by emerging pathogens are episodic, by definition difficult to predict.
These realities notwithstanding, certain key steps can build towards a strategic approach.
The U.S. government needs to lead with sustained funding commitments for “orphan” pathogens such as Ebola. This will be critical to building industry confidence in its own long-term engagement. In the past, stop-and-go U.S. funding has led to episodic industry commitments.
For industry’s part, it needs to make R&D for emerging threats an integral part of its business model. This will involve building stronger R&D platforms drawing from a network of diverse industry capacities that can facilitate early and quick responses. Mr. Malpani of MSF emphasized the need to ensure the affordability and accessibility of products that serve these shared global health interests.
Formidable challenges lie ahead in West Africa.
A major unresolved debate is unfolding over how field trials for Ebola vaccines are to be conducted, effectively and ethically, while winning the trust and confidence of communities. As trials unfold in 2015, there will be continued tension and controversy.
One argument is that gold standard for field trials – randomized, double-blind, placebo trials – must be applied in order to generate accurate and reliable knowledge of the true safety and efficacy of vaccine candidates. It is important to differentiate between unproven vaccines, which are delivered to healthy individuals, versus unproven treatments that are delivered on a “compassionate use basis” to very ill individuals who are at risk of dying. It is also important to recall the precedent of an HIV/AIDS vaccine that at first appeared promising, was given to patients before being fully tested, and was eventually proven harmful.
An opposing argument is that compromise and pragmatism – developing workable field trial methods that diverge from the gold standard – are inevitable and necessary, given the broad popular fear and stigma generated by Ebola; profound distrust of governments, including health providers, in Liberia, Sierra Leone and Guinea; and exceptionally difficult operational environment in these countries.
As 2015 unfolds, deliberations will intensify among national leaders, community elders, and others over how trials are to be conducted ethically, and how communities can willingly agree to enter trials. Resolution of these issues will be complicated and take time.
In the long term, should a viable vaccine(s) be developed and distributed, other important considerations will come to the fore: the need for guaranteed, affordable access to vaccines and therapies, including first responder organizations such as MSF; the challenges of equitable supply (as many developed countries will likely want to establish their own stockpiles) and prioritization of affected communities; improving supply chains to the community level; and ensuring the production of second generation vaccines with improved thermal stability.
This pivotal moment is remarkable for the hope, optimism, and determination it has triggered for the accelerated, cross-sector development of an Ebola vaccine. Yet these aspirations are muted by a continued uncertainty that hangs over the entire enterprise. The conspicuous failure of preparedness in 2014 has stirred new thinking about how to organize strategically for the future. The advent of field trials in 2015 has brought forward a major debate over what is possible and essential, on ethical, scientific, and political grounds, to determine if a truly viable vaccine exists. For all of these reasons, 2015 will be a very important year.