What are the lessons learned from the COVID-19 response for treating new emerging infectious diseases?
Scientists began work on the COVID-19 vaccine in January 2020. Dedicated vaccine funding helped move vaccine candidates through the preclinical/clinical assessments at an unprecedented speed, enabling researchers to advance into phase 3 clinical trials in six months instead of the typical two years. This speed was accomplished through several modifications to the typical drug development cycle. The lessons learned through these modifications, among dozens of other biotechnology-focused topics, were discussed at the 2021 American Association of Pharmaceutical Scientists (AAPS) National Biotechnology Conference (NBC) held virtually May 17-20, 2021.
Emergency measures
Operation Warp Speed provided $18 billion in funding for development of vaccines that were intended for U.S. populations. As explained by Bryan Harmon from Eli Lilly during NBC, this funding allowed vaccine producers to eliminate money as a constraint and accelerate scope and timing to viable treatment candidates. This public-private partnership has included vaccines and monoclonal antibody treatments, and it has enhanced CDMO manufacturing capacity and raw material supply. This allowed the manufacture of at-risk clinical materials before clinical data were available and allowed production of commercial product prior to approval for distribution. Front loading of many CMC and manufacturing activities was critical to the rapid response. Harmon used these strategies to reduce the timeline for cell line transfection to first human dose from a typical 17 months to 2 months.
Additionally, the Emergency Use Authorization (EUA) process allows the department of Health and Human Services (HHS) to request the Food and Drug Administration (FDA) to authorize unapproved medical products to be used as counter measures in public health emergencies. These requests were initially focused on terrorism and worries of a potential biological or radiation weapon being used against the U.S. or U.S. allies. Over time, legislation has addressed how the EUA process works, but at its core, it starts with the emergency declaration from the HHS secretary after concluding that there is a public health emergency that could be a threat, recently such as Ebola, Zika, and COVID-19. FDA moves EUA reviews to the top of the queue and employs an all-hands-on-deck resourcing approach to get the reviews done quickly. For example, the RNA lipid nanoparticles and their ability to be applied to new indications—like COVID-19 mRNA vaccines—was recently authorized under an EUA. Related, parallel workflows were recently used to rapidly deliver monoclonal antibody therapeutics for COVID-19.
An expedited response
Adaptive clinical trial designs were also used to increase the speed of vaccine development. An adaptive design uses ongoing generated data to modify the trial design in real time. These modifications could include dosage, sample size, and patient inclusion criteria. Bamlanivimab, a monoclonal antibody treatment for COVID-19, was rapidly developed using this method. Preclinical data was used for modeling and simulation, and it was used cumulatively with clinical data generated in an adaptive design to develop this therapy.
Another major consideration for approval is the availability of long term safety data and whether the shortened development time compromises patient safety. Other novel biologics that eleicit a similar immune response to COVID-19 infection can be leveraged to risk mitigate the lack of these safety data.
Even though unlimited money may not be available for every disease, the COVID-19 experience does show that there are lessons to be learned for drug developers. As discussed throughout NBC, parallel development activities, prudent risk taking, predictive modeling, and adaptive clinical designs are lessons that can be leveraged for other product candidates as well.
