Avoid clinical trial ‘valley of death’ with medical countermeasure program

Associated Press/Charles Krupa
Pharmacist Sima Manifar prepares a children’s dose of the Pfizer COVID-19 vaccine during a vaccination clinic at City of Lawrence’s “The Center,” which serves seniors, families and the community, Wednesday, Dec. 29, 2021, in Lawrence, Mass. Pfizer has begun a study comparing its original COVID-19 vaccine with doses specially tweaked to match the omicron variant.…

The COVID-19 pandemic has put us on notice. It is critical to health and national security for the U.S. to prepare for the inevitable future infectious disease emergencies that will occur. It is clear that vaccines, antivirals, monoclonal antibodies and diagnostics are key components of preparedness and response. And we cannot relent, assuming another coronavirus will ignite the next pandemic. There are other threats out there. The United States needs to launch a strategic effort to create the capability to proactively develop a robust pipeline of products targeted toward the high consequence viral families most likely to cause a pandemic.

While it is impossible to know precisely what the next pandemic pathogen will be — “Disease X” is likely to arise from one of several viral families that include efficiently spreading respiratory viruses some of which may be highly transmissible and lethal. Right now, the U.S. remains vulnerable to the next novel pathogen because there is no sustained federal funding, program or strategy dedicated to accelerating the advanced development of medical countermeasures for such a Disease X virus.

What is stopping government, academia and industry from commencing this important work? The answers are many — the absence of a coordinated government strategy; the scientific complexity of the mission; limited resources; and the lack of a clear commercial market that could drive investment. The list goes on.

There is now hope that Congress will address these impediments. The bipartisan PREVENT Pandemics Act, currently being considered by Congress, directs the National Institutes of Health (NIH) director to develop a ”multidisciplinary research program to advance the discovery and preclinical development of medical products for priority virus families and other viral pathogens with a significant potential to cause a pandemic, through support for research centers.” As part of this program, the NIH director is to partner and coordinate with other agency chiefs.

This is exactly what is needed for early-stage development of medical products for a future Disease X, but it is only one aspect of the multi-stage process. 

Stopping at preclinical development of promising products only gets us (almost) halfway there if our national goal is to be optimally prepared for the next threat. As the PREVENT Pandemics Act moves through the legislative process it is imperative that the act includes specific funding and a clear remit to the Biomedical Advanced Research and Development Agency (BARDA) to launch a “Disease X” medical countermeasure development program. Sen. Tammy Baldwin (D-Wis.) introduced a bill, the Disease X Act, last summer that calls for the creation of this program.

Medical countermeasure development is well known to be a high risk undertaking that typically requires significant investment at all stages of development. There are products that make it through preclinical development successfully but falter when it comes to clinical trials and late phase development. Some products and platforms are highly scalable for surge manufacturing, but many are not, and this also must be carefully addressed during this later stage. This chasm between preclinical and clinical development is colloquially referred to as the “valley of death” as products can easily die at this stage.

With biodefense — preparation against potential biological weapons such as anthrax and smallpox — it was quickly realized that unless products were pulled through the “valley of death” the U.S. would be left without any products that could be quickly deployed to mitigate the impacts of a biological attack. Preclinical development would never be enough and because many of these products had no commercial market (as the diseases they addressed are thankfully not everyday occurrences), a comprehensive solution was required.

In 2006, President George W. Bush signed the Pandemic and All Hazards Preparedness Act (PAHPA) which, among myriad other things, established BARDA. BARDA has a mission “to develop and procure medical countermeasures that address the public health and medical consequences of chemical, biological, radiological, and nuclear (CBRN) accidents, incidents and attacks, pandemic influenza, and emerging infectious diseases.”

Specifically, BARDA is an advanced development agency  — emphasis on advanced — which bridges across the “valley of death.” As such they have ample experience working with small and large biotech and pharmaceutical companies with promising technologies. These are not early-stage development ideas or basic scientific research. BARDA works with commercial companies of various sizes in a more mature stage of development, while NIH typically works with university-based researchers doing cutting-edge basic science. 

To date, BARDA has been integrally involved in the FDA licensure, approval and clearance of over five dozen medical countermeasures. This speaks to their vital role in bringing actual products — against pressing health and biosecurity threats — to fruition. It is the mission they were constituted to fulfill. 

BARDA should not be relegated to a junior partner role, cc’d on emails. To advance the national goal of having safe and effective medical products that are ready to be surge produced in the face of a future pandemic, Congress should ensure that BARDA is specifically tasked in the PREVENT Pandemics Act with executing an advanced development program for Disease X medical countermeasures so that they aren’t interminably mired in the “valley of death” when the next infectious disease emergency surfaces.

Amesh Adalja, M.D., is an infectious disease physician and a senior scholar at the Johns Hopkins Center for Health Security.

Anita Cicero, JD is deputy director at the Johns Hopkins Center for Health Security and a senior scientist at the Johns Hopkins Bloomberg School of Public Health.

Tags Amesh Adalja Anita Cicero Clinical trial COVID-19 Infectious disease NIH Pandemic Tammy Baldwin

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