COVID-19 is highlighting the challenges of providing timely availability of diagnostics, therapeutics and vaccines.
The biopharma industry has accelerated research and development (R&D) timelines. However, therapeutics/vaccines in development are projected to launch after more than 260,000 lives have been lost globally.
Existing policies, government and biopharma industry processes do not sufficiently address the rapid need for diagnostic, vaccine and therapeutic development.
New business models, public/private investment strategies and investment in platform technologies from multiple sectors are needed to more effectively create a timely R&D response.
The current COVID-19 pandemic is a global humanitarian crisis that has impacted every aspect of society, from health to the economy to working and living styles, in ways that were unimaginable just weeks ago and that continue to evolve rapidly. The biopharma industry has stepped up to global calls for research, development and manufacturing support related to COVID-19 at breakneck speed; however, therapeutics and vaccines in development will eventually launch well after more than 260,000 lives have already been lost globally.
Infectious diseases, including COVID-19, represent a threat to every part of the globe and have the potential to spread at a breathtaking pace in our modern, interconnected society. Since 2000, the world has seen several viral outbreaks, including severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and Ebola, each with pandemic potential. Beyond threats that have already seen sustained human transmission, the World Health Organization (WHO) has identified a range of priority pathogens that have yet to fully break out, further solidifying that while the timing of the next pandemic is unpredictable, it is inevitable that one will occur.
There is a range of better-understood and -characterized pathogens, including seasonal influenza (approximately 290,000-650,000 worldwide deaths per year) and antimicrobial resistance (AMR) (roughly 700,000 worldwide deaths per year), with far-reaching impacts. Both the flu and AMR result in significant loss of life each year, demonstrating that awareness alone will not spur the needed societal and industrial preparation and response. To this end, L.E.K. Consulting has identified a number of lessons for future pandemic preparedness based on both COVID-19 and prior outbreaks.
With more than 3.7 million confirmed cases, 260,000 deaths globally to date, vast numbers of jobs lost and billions of lives affected, the scale and scope of destruction wrought by COVID-19 have already far surpassed any disease outbreak in modern memory, and thus the pandemic has no single analog for considering how policymakers and private industry should respond (see Figure 1). There are, however, lessons learned from prior outbreaks, including Ebola (2013-16, 2018-present) and H1N1 (2009), that can help contextualize and guide responses to COVID-19.
COVID-19 has amplified the challenges of preparing for future outbreaks
In our assessment, we highlight five critical challenges to a rapid and scaled pandemic response that exist before, during and after an outbreak occurs (see Figure 2). These barriers have implications for how the biopharma industry can respond to the next pathogen with pandemic potential.
There is no pre-outbreak globally agreed-upon trigger to galvanize the biopharma industry’s R&D efforts
The Ebola epidemic began in December 2013. There was, however, little global action triggered until the WHO declared a Public Health Emergency of International Concern in August 2014, which helped spur industry response. Similarly, the first COVID-19 case came in mid-November, while therapeutic R&D did not engage until mid-January. Creating international standards to serve as agreed-upon R&D triggers for incipient outbreaks can help reduce this time lag and ultimately save lives.
The lack of a trigger to mobilize efforts also applies to non-incipient outbreaks. The WHO has short-listed 10 diseases that could be the next pandemic on its “R&D Blueprint.” Despite representing the next wave of threats, many have seen minimal investment. Crimean-Congo hemorrhagic fever, for example, is the subject of only one active clinical trial. For a disease with a 10%-40% mortality rate and presence across Asia, the Balkans, the Middle East and Africa, this is a stark underinvestment relative to the global risk.
The typical life cycle of an outbreak creates a timing mismatch between initiating R&D and worldwide, commercial-scale production
Ebola saw sporadic cases prior to the 2013-16 West African outbreak, with the next outbreak purely a matter of “when, not if.” However, less than $40 million worldwide per year was invested to reduce this risk prior to the 2013 outbreak. Investment soared post-outbreak, but could not overcome the timing mismatch. When trials began in 2015, the bolus of patients had already been diagnosed and treated (either with unapproved therapies, often as observational studies, or with palliative care), and several trials were unable to attract enough patients.
H1N1, however, did not suffer from a comparable timing mismatch — in fact, it took just six months from the start of the outbreak to develop four vaccines. This rapid timeline was enabled by longstanding government and private investment in the seasonal influenza vaccine (e.g., approximately $3.1 billion in cumulative National Institutes of Health influenza research funding from 2010-19 alone). Once strain-specific antigens to target were identified, existing processes and “muscle memory” were activated to develop, test and manufacture a vaccine. U.S. Food and Drug Administration (FDA) approval was also rapid, as clinical outcome studies were not required given H1N1’s similarity to prior flu vaccines.
Information deficits for breadth, severity and mechanism of a pathogen present headwinds to R&D, despite laudable efforts of the biopharma industry to address these pathogens quickly and inventively
Unlike in prior outbreaks that did not see such a broad industry response, the biopharma industry has responded incredibly rapidly to develop COVID-19 treatments (see Figure 3). The speed at which COVID-19 has expanded across the globe relative to prior disease outbreaks has overcome typical barriers to kick-starting R&D, to the credit of the entire industry, despite an initial lag between Patient Zero and global dissemination of the viral sequence.
There are already 63 vaccines and 108 therapeutics in development for COVID-19 and more expected to follow (as of April 3). A staggering 300 clinical trials for COVID-19 are slated to have already started, representing roughly 10%-15% of the typical total number of trials started over a four-month period (see Figure 4). Compared with Ebola, which saw two primary vaccine candidates and five therapeutics, this response is unprecedented. Of the 108 COVID-19 therapeutics, 43 agents have been repurposed from other indications, including HIV and influenza, helping rapidly expand the therapeutic pipeline. This growth is particularly impressive, as the genetic sequence for COVID-19 was not disseminated until Jan. 11, approximately two months after Patient Zero was identified.
Repurposing therapeutics is one way private industry can help close the development gap. Gilead’s antiviral remdesivir has seen extensive coverage after being repurposed from Ebola to COVID-19. Machine learning and artificial intelligence capabilities within drug development are still at a nascent stage, but they could offer a road map for both COVID-19 and subsequent outbreaks by rapidly comparing the off-target effects of drugs, both old and new, against the next virus.
During an outbreak, clinical trial design and execution are incredibly difficult and require global coordination to work through unclear scientific and clinical parameters across geographies
The inherent timing pressure of operating trials to address a pandemic, coupled with imperfect information about disease epidemiology, complicates every aspect of trials, from biomarker identification for enrollment to treatment arms (e.g., use of a placebo control) to data standardization and results reporting. Trial enrollment, in particular, requires agreement across regions/countries on standardized diagnostic tools and metrics to identify trial participants.
There have been a number of efforts to foster a cohesive and rapid therapeutic development process worldwide for COVID-19, including the WHO’s global trial (SOLIDARITY) and National Institute of Health’s (NIH) Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV). SOLIDARITY is testing the safety and efficacy of four drugs or drug combinations in concert with over 90 contributing countries to date, while the NIH’s ACTIV has partnered with 16 pharmaceutical companies to standardize research efforts across stakeholders and better prioritize high-potential efforts. Biopharma’s existing expertise in conducting global trials can serve as a valuable asset in codifying these efforts into part of the future outbreak blueprint (e.g., development and expansion of patient-trial matching platforms).
Across outbreak stages, the current system does not sufficiently incentivize the private sector to mobilize R&D efforts and follow-through to approval
There is no obvious track record of regulatory approval or commercial success for therapeutics and vaccines during recent disease outbreaks, and this dynamic highlights the lack of incentives to follow through with R&D efforts. Nearly two decades after the outbreak of SARS in 2003, there are still no approved therapies. MERS, first identified in 2012, also has no approved therapies. While Ebola has one vaccine, Ervebo, it was not FDA approved until December 2019 — a full six years after the West African outbreak — and there are still no approved therapeutics.
There are myriad factors further complicating the incentive structure, including:
- Unclear scale and spread of the outbreak and therefore undefined scope of need for pharmaceutical intervention (e.g., the self-limiting nature of MERS subsequently constrained infection growth)
- Inadequate incentives and economics for private industry to fund and develop therapies and vaccines to address hypothetical future outbreaks, with large capital needs and a high risk profile vs. other investment areas
- Rapid manufacturing at a massive scale requires an upfront capital and organizational commitment to expand supply chain capabilities
The economic structure under which the biopharma industry operates is subject to a number of stakeholders — governments, nongovernment organizations (NGOs), payers, academic partners and others — and will likely require a broad consensus across stakeholders on how to rework incentives moving forward. In the short term, however, progress has been made — the U.S. coronavirus relief bill, for example, allocated $3.5 billion to the Biomedical Advanced Research and Development Authority (BARDA) to support building scaled manufacturing preapproved for certain COVID-19 therapeutics.
We can shift how we prepare for and respond to future outbreaks
More needs to be done to enable a rapid and scaled response to threats. As we cannot predict the specific disease, we need to build systems, processes and technologies to enable a rapid response that is flexible to address a wider range of potential threats.
Based on prior outbreaks, COVID-19 and industry expertise, we have identified three areas that can help ensure we are better prepared for the next outbreak (see Figure 5):
Elevate public health surveillance to better understand the epidemiology and evolution of diseases, including improved sharing of clinical and scientific data across NGOs, governments and private partners
Ultimately, the biopharma industry cannot mobilize rapidly to address an outbreak if the front-line monitoring does not promptly identify potential outbreaks. The Global Health Security Agenda, formed in 2014, has worked with the Centers for Disease Control and Prevention (CDC) to help countries enhance surveillance and monitoring for infectious diseases. Worldwide surveillance — and prompt data reporting — should be a priority for all stakeholders and requires international collaboration to ensure all governments are reporting in a structured, rapid fashion.
Enlist the power of the private sector to support drug and platform development, as well as scalable diagnostic testing support
Vaccines and therapeutics garner the most attention as an outbreak progresses, and the response from the biopharma industry so far during the COVID-19 outbreak has been as impressive as it is encouraging. Partnerships between biopharma and the public sector (e.g., BARDA and Regeneron and Janssen, the Defense Advanced Research Projects Agency and Moderna) and the NGO sector (e.g., the Coalition for Epidemic Preparedness Innovations and CureVac, Inovio and Novavax, and the Wellcome Trust and Novartis) are major contributors to the speed and breadth of the biopharma COVID-19 response, from which any therapeutic or vaccine is likely to emerge. Diagnostics, on the other hand, which are crucial to supporting testing, surveillance and myriad R&D processes, have not realized the same dynamic. In particular, U.S. COVID-19 patient testing saw extensive delays and capacity constraints when the burden was shouldered exclusively by the CDC. Slow approval of tests from diagnostic companies limited the ability of the private sector to support testing efforts, despite the fact that companies (e.g., Abbott, Novacyte) were able to develop rapid tests and devices. Broad and deliberate involvement of the private sector from the earliest signs of pandemic potential, from diagnostics to drug development, is necessary to overcome the challenges of timing and scale posed by such outbreaks.
A key driver to unlock the power of the private sector is to address existing economic barriers, risks and returns on investment for innovators. In particular, government and NGO programs and partnerships can provide key economics to innovative biopharma companies to offset capital needs and risk of pandemic-related development efforts vs. other more-predictable areas of investment and return.
Double down on select platform technologies that enable rapid drug development while remaining pathogen-agnostic
Platform technologies can help enable a more flexible and dynamic response to the next disease outbreak. For example, Moderna’s messenger RNA platform — while still unproven — had the first human COVID-19 vaccine in trials within days of sequence availability and could represent a go-forward vaccine model for future outbreaks. Therapeutics can benefit from similar structural thinking — for example, antivirals that disrupt cells’ ability to assist in viral replication (i.e., “host targeted” therapies) rather than virus-specific efforts.
While the COVID-19 pandemic is still evolving, there are reasons for optimism in terms of having lifesaving therapeutic and preventive vaccine options emerge as we go forward — a forthcoming L.E.K. Executive Insights will further detail this development pipeline and progression. But the global toll taken by COVID-19 on human life, as well as the economies that underpin sustained human welfare, will be profound and lasting. Through concerted government, NGO and life sciences industry focus on the barriers discussed herein, and other enabling technologies such as rapid diagnostics, the pandemic potential for future high-threat pathogens can be suppressed long before reaching COVID-19-like impact.
Editor’s note: Pandemic Preparedness During COVID-19: Biopharma Lessons and Future Implications was co-authored by Kevin Giffels, a Senior Associate Consultant in L.E.K. Consulting’s Life Sciences practice. Kevin is based in Boston.