Successful Treatment of Prolonged, Severe Coronavirus Disease 2019 Lower Respiratory Tract Disease in a B cell Acute Lymphoblastic Leukemia Patient With an Extended Course of Remdesivir and Nirmatrelvir/Ritonavir.

A patient with B-cell acute lymphoblastic leukemia (ALL) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had persistent, progressive pneumonia with viremia after 5 months of infection despite monoclonal antibodies, intravenous (IV) remdesivir and prolonged oral steroids. Twenty days of nirmatrelvir/ritonavir and 10 days of IV remdesivir led to full recovery.

Healthcare on the brink: navigating the challenges of an aging society in the United States.

The US healthcare system is at a crossroads. With an aging population requiring more care and a strained system facing workforce shortages, capacity issues, and fragmentation, innovative solutions and policy reforms are needed. This paper aims to spark dialogue and collaboration among healthcare stakeholders and inspire action to meet the needs of the aging population. Through a comprehensive analysis of the impact of an aging society, this work highlights the urgency of addressing this issue and the importance of restructuring the healthcare system to be more efficient, equitable, and responsive.

Master protocols and other innovative trial designs in inflammation and immunology to expedite clinical drug development.

Master protocol designs, such as umbrella and basket studies, allow multiple compounds or multiple target populations to be evaluated simultaneously within a single protocol, and have been widely adopted in oncology clinical trials. These novel designs can also be applied in other therapeutic areas, where they could have several benefits over conducting traditional randomized controlled trials. Here, we detail Pfizer's recent implementations of master protocol designs in inflammation and immunology clinical studies, focusing on the opportunities for cost and resource savings and how these designs can expedite the time required to bring new treatments to patients in need.

Rewriting the textbook for pharma: how to adapt and thrive in a digital, personalized and collaborative world.

The pharmaceutical industry is undergoing a sweeping transformation, driven by technological innovations, demographic shifts, regulatory changes and consumer expectations. For adaptive players in pharma to excel in this rapidly changing landscape, which will be markedly different from today by 2030 and beyond, they will require a different set of skills, capabilities and mindsets, as well as a willingness to collaborate and co-create value with multiple stakeholders. The industry needs to rewrite the textbook for pharma by embracing and implementing four key dimensions of change: digitalization, personalization, collaboration and innovation. In this article, we will examine how these dimensions of change are reshaping the industry, and provide practical and strategic guidance based on best practices and examples. Specifically, adaptive pharma companies should embrace the use of advanced digital technologies, such as artificial intelligence and machine learning technologies, to streamline processes and solve challenges rapidly. Personalization, both in medicine and patient engagement, will also be key to success in the 'digital revolution', and a collaborative approach involving partnerships with tech start-ups, health-care providers and regulatory bodies will also be essential to create an integrated and responsive health-care ecosystem. Using these ideas for a rewritten textbook for pharma, adaptive players in pharma will evolve to be personalized and digitized health-focused organizations that provide comprehensive solutions which go beyond drugs and devices.

Breaking the mold with RNA-a "RNAissance" of life science.

In the past decade, RNA therapeutics have gone from being a promising concept to one of the most exciting frontiers in healthcare and pharmaceuticals. The field is now entering what many call a renaissance or "RNAissance" which is being fueled by advances in genetic engineering and delivery systems to take on more ambitious development efforts. However, this renaissance is occurring at an unprecedented pace, which will require a different way of thinking if the field is to live up to its full potential. Recognizing this need, this article will provide a forward-looking perspective on the field of RNA medical products and the potential long-term innovations and policy shifts enabled by this revolutionary and game-changing technological platform.

Deciphering immune responses: a comparative analysis of influenza vaccination platforms.

Influenza still poses a significant challenge due to its high mutation rates and the low effectiveness of traditional vaccines. At present, antibodies that neutralize the highly variable hemagglutinin antigen are a major driver of the observed variable protection. To decipher how influenza vaccines can be improved, an analysis of licensed vaccine platforms was conducted, contrasting the strengths and limitations of their different mechanisms of protection. Through this review, it is evident that these vaccines do not elicit the robust cellular immune response critical for protecting high-risk groups. Emerging platforms, such as RNA vaccines, that induce robust cellular responses that may be additive to the recognized mechanism of protection through hemagglutinin inhibition may overcome these constraints to provide broader, protective immunity. By combining both humoral and cellular responses, such platforms could help guide the future influenza vaccine development.

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

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.

Reviving an R&D pipeline: a step change in the Phase II success rate.

The pharmaceutical industry has faced declining research and development (R&D) productivity for decades. During the early 2010s, Pfizer saw its R&D productivity drop even more sharply than did its industry peers. As impactful medicines the company had developed and brought to patients in previous years lost exclusivity, Pfizer faced a steep patent cliff with a cumulative revenue impact of >US$28 billion through 2018. Since 2010, the company has embarked on a focused turnaround effort to improve R&D productivity. Although some efforts will need more time to prove themselves, there are early signs of a turnaround now, particularly in terms of Phase II success rates. Here, we share some learnings from a decade of experience as one of the largest R&D organizations in the industry.

Innovation in breakthrough drugs and vaccines: Development risk, patient impact, and value.

Innovation has a crucial role in developing breakthrough drugs and vaccines that can change patients' lives. To better understand this role, we evaluated recent outcomes for assets developed using different types of innovation. Although all approaches have delivered breakthroughs, assets that modulate established biological targets with innovative scientific or technological designs provide a unique combination of reduced development risk, high patient impact, and high commercial value. This type of asset currently represents a relatively small proportion of approved drugs and vaccines, but we anticipate that an increasing body of scientific knowledge and ongoing technological advancements could offer opportunities to grow this category in the future.

Precision medicine: an approach to R&D for delivering superior medicines to patients.

Pharmaceutical R&D productivity has declined over the last decade despite increasing investments. Recent trends, however, indicate a potential reversal of this trend fueled by a wave of new biologics, vaccines and highly selective NCEs directed against targets validated by human genetics, focus on new disease areas including orphan and genetic diseases and more precise tailoring of medicines to their target populations.