Achieving end-to-end success in the clinic: Pfizer’s learnings on R&D productivity

Abstract

Over the past decade, Pfizer has focused efforts to improve its research and development (R&D) productivity. By the end of 2020, Pfizer had achieved an industry-leading clinical success rate of 21%, a tenfold increase from 2% in 2010 and well above the industry benchmark of ∼11%. The company had also maintained the quality of innovation, because 75% of its approvals between 2016 and 2020 had at least one expedited regulatory designation (e.g., Breakthrough Therapy). Pfizer’s Signs of Clinical Activity (SOCA) paradigm enabled better decision-making and, along with other drivers (biology and modality), contributed to this productivity improvement. These laid a strong foundation for the rapid and effective development of the Coronavirus 2019 (COVID-19) vaccine with BioNTech, as well as the antiviral candidate Paxlovid™, under the company’s ‘lightspeed’ paradigm.

Probability of Success in Drug Development

“…Pfizer recently shared its learnings on increasing “end‐to‐end” success, which is currently almost twofold higher than the industry benchmark; whereas, in the previous decade it was consistently lagging behind its peers 3 . A major driver for this turnaround was a remarkable increase in phase II success, which is currently 50% higher than that of the rest of the industry 3,4 . The company has described the three building blocks behind its increased R&D productivity as follows: Biology: deeper understanding, emphasis on science, and sharper focus on specific therapeutic areas; Modalities: broadening the toolbox to a range of modalities beyond small molecules; and Decision making: incorporating more systematic and consistent use of quantitative metrics. …”

“…It has been suggested that 60% of all research and development (R&D) costs are due to attrition. 3 However, obtaining a single estimate of PoS is not trivial, since a variety of diverse elements need to be considered and integrated. Thus, the definition of "success" is multifactorial and includes technical, medical, regulatory, and commercial success.…”

“…At this stage, the stakes (costs) are high and ~ 90% of drug candidates fail during clinical development. It has been suggested that 60% of all research and development (R&D) costs are due to attrition 3 . However, obtaining a single estimate of PoS is not trivial, since a variety of diverse elements need to be considered and integrated.…”

“…but expands the utility to earlier phases of development through, for example, the “3 Pillars” and “Signs of Clinical Activity (SoCA)” paradigms. Due to this more holistic approach, the concept of PoS can be expanded to “quality of success” 3 (QoS; Figure ).…”

Oral Nirmatrelvir/Ritonavir Therapy for COVID-19: The Dawn in the Dark?

“…Among these new drugs, the oral form nirmatrelvir/ritonavir provides the most promising therapeutic effect, an 89% reduction in the risk of hospitalization or death [ 7 , 9 , 12 ] ( Figure 1 ). Nirmatrelvir/ritonavir have been expected to change the course of the COVID-19 pandemic [ 13 , 14 ].…”