A lightspeed approach to pandemic drug development

Pfizer had successes during COVID-19 by streamlining decisions and running several steps in parallel, a lightspeed approach that can be applied to other diseases. Before the COVID-19

pandemic, the end-to-end timeline for bringing vaccine and drug candidates from discovery to market could take 10 to 15 years, or more. However, this paradigm changed when the SARS-CoV-2

virus was identified as an imminent, worldwide threat. Pfizer’s pandemic response — via external partnership, reduction of bureaucracy, and a purpose-driven culture — exemplifies this shift,

and provides real-world lessons on how to help avoid a regression to pre-pandemic ways. Credit: Jean Terman External factors that facilitated this included global sharing of the genome

sequence; existing mRNA-related technologies for vaccine development; and earlier coronavirus work (including research by the National Institutes of Health on stabilizing spike proteins)

that informed vaccine design and research. Meanwhile, Pfizer’s own facilitating factors included deep investments over the past decade in research and development infrastructure; extensive

experience in infectious disease research; talented, agile teams of scientists, engineers, physicians and staff; and therapeutic proof-of-concept for protease inhibitors designed against

SARS-CoV-1. Despite these advantages, many challenges loomed. The mRNA approach was unproven, and early vaccines and monoclonal antibody treatments could not account for antigenic change. In

the spirit of the adage about desperate times, Pfizer took a creative approach to maximize the facilitating factors, while mitigating the challenges that remained. The rapid pace with which

Pfizer and its collaborator, BioNTech, developed, tested, manufactured and marketed their COVID-19 vaccine, BNT162b2 (Comirnaty), demonstrated that this process can be markedly shortened by

streamlining decision-making and running several steps in parallel. This approach, which we termed ‘lightspeed’, was similarly used to develop the oral COVID-19 treatment nirmatrelvir and

ritonavir tablets (Paxlovid). For Comirnaty, Pfizer’s collaboration with BioNTech leveraged the strength of both companies to rapidly develop the vaccine: mRNA experience for BioNTech and

vaccine research and development for Pfizer. For Paxlovid, Pfizer used in-house experience with protease inhibitors, as well as AI- and structure-based small-molecule design to invent a main

protease (Mpro) inhibitor that limited the risk of causing resistance. For both modalities, academic partnerships were instrumental in generating data with collaborating coronavirus experts

with biosafety level 3 (BSL3) facilities. The clinical and product-development paradigms were similar for Comirnaty and Paxlovid, with resource investment and allocation that far exceeded

the norm, and little evidence that either modality would work. Both had expedited clinical programs, with more clinical sites than would normally be deployed. For Comirnaty, a seamless phase

I–III clinical study was conducted with several candidates tested simultaneously during phase I. This eliminated the usual transition periods between phases and was achieved in consultation

with regulatory agencies. For Paxlovid, an adaptive design led to dose selection and to the inclusion of ritonavir to maximize exposure of nirmatrelvir. While existing infrastructure

supported the lightspeed approach, changes in Pfizer’s governance structure promoted a clear mission and unified set of goals. The result was a purpose-driven culture that matched the

urgency of the approach. Vaccine and Hospital (anti-infective) area heads representing different functions met whenever needed to assess opportunities and drive rapid decision-making within

and across lines. These meetings were followed by almost daily check-ins with Pfizer chief scientific officer Mikael Dolsten and weekly meetings with Pfizer chief executive officer Albert

Bourla and key members of his leadership team, to review activities and obtain endorsements in real-time. Meeting preparations were minimal in favor of clear, constant communication across

the organization. At the same time, Pfizer worked externally with regulators such as the US Food and Drug Administration to ensure that the data from any successful programs were sufficient

to support making the product rapidly available to patients. Development and supply timelines were driven by manufacturing. With a limited supply chain and accelerated development process,

the supply of final products initially lagged. Despite these challenges, Pfizer achieved in mere months what usually takes years: scaling-up processes from gram-quantities to the tons

required to help supply the globe. The people component cannot be underestimated. Colleagues were highly committed and challenged existing assumptions about what was possible. Preventing

burnout was a huge concern, as was learning how to adjust work schedules when pandemic restrictions lifted. More than two years after the pandemic began, there are at least 27 vaccines, one

monoclonal antibody and three therapies with antiviral activity available. Although this should be celebrated, it is a drop in the ocean compared with the global effort to overcome this

public-health emergency. As we now enter a new era in drug development, the challenge is to apply this lightspeed approach across more therapeutic areas to lifesaving medicines for the

patients who need them the most. ACKNOWLEDGEMENTS A.G. Wexler provided editorial support. Note that emergency use of Comirnaty has not been approved or licensed by the US FDA, but has been

authorized to prevent COVID-19 in individuals aged over 6 months. Paxlovid is not approved, but is authorized for emergency use by the FDA to treat mild-to-moderate COVID-19 in high-risk

patients aged 12 years and over, weighing at least 40 kg, with positive results of SARS-CoV-2 viral testing. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Worldwide Research, Development

& Medical, Pfizer Inc., Pearl River, NY, USA Annaliesa S. Anderson Authors * Annaliesa S. Anderson View author publications You can also search for this author inPubMed Google Scholar

CORRESPONDING AUTHOR Correspondence to Annaliesa S. Anderson. ETHICS DECLARATIONS COMPETING INTERESTS A.S.A. is a fulltime employee of Pfizer and owns shares in the company. RIGHTS AND

PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Anderson, A.S. A lightspeed approach to pandemic drug development. _Nat Med_ 28, 1538 (2022).

https://doi.org/10.1038/s41591-022-01945-6 Download citation * Published: 11 August 2022 * Issue Date: August 2022 * DOI: https://doi.org/10.1038/s41591-022-01945-6 SHARE THIS ARTICLE Anyone

you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by

the Springer Nature SharedIt content-sharing initiative