Antibiotic Development: Lessons from the Past and Future Opportunities.

The challenge of antimicrobial resistance is broadly appreciated by the clinical and scientific communities. To assess progress in the development of medical countermeasures to combat bacterial infections, we deployed information gleaned from clinical trials conducted from 2000 to 2021. Whereas private sector interest in cancer grew dramatically over this period, activity to combat bacterial infections remained stagnant. The comparative ambivalence to antimicrobial resistance is reflected in the number of investigative drugs under clinical investigation, their stage of development and most troublingly, a declining number of organizations that are actively involved in the development of new products to treat bacterial infections. This drop reflects the exits of many companies that had previously developed antibacterial agents.

2023 in review: FDA approvals of new medicines.

An analysis of all new entities approved by both the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) identified the approval of 69 new entities in the year 2023, 50 % more than in the previous year. Oncology drugs tied with congenital and infectious diseases drugs for the most approvals. Although orphan and priority approvals continued at a high pace, the rate of fast-track approvals continued to decline. The rate of industry consolidation also picked up again after decreasing slightly in 2022.

WANTED DEAD OR ALIVE: New Thinking to Incentivize Drug Development.

Despite unprecedented advancements in our understanding of disease process and targeting opportunities, our continued ability to discover and develop new medicines is fundamentally in doubt. These challenges reflect a growing recognition of the escalating risks of drug development (in terms of dollars and time) by established pharmaceutical companies and investors. Such hurdles are surmountable and require new thinking. This opinion piece conveys an overview of the challenge and an example of how we might overcome these challenges with constructive and forward-looking incentives for drug discovery.

2022 in review: FDA approvals of new medicines.

An accounting of all new entities approved by both the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) identified the approval of 44 new entities in the year 2022. Oncology-based drugs continued to be the most popular indication for these medicines. Likewise, orphan indications encompassed more than half of new drug approvals. The number of new entities approved in 2022 declined from its peak after 5 years of more than 50 annual approvals. Likewise, the rate of consolidations slowed somewhat, among both new entries in the realm of clinical-stage developers and more established organizations.

Monoclonal antibodies: Trends in therapeutic success and commercial focus.

Monoclonal antibody products have risen from obscurity in the 1990s to a position that increasingly dominates both revenue generation and patient impact. This success has occurred largely over the past two decades, and we have identified factors associated with the remarkable advances that have contributed to the discovery, development and approval of monoclonal antibodies. Although consolidation has increased in recent years, the net number of monoclonal antibody developers continues to grow, bucking the general trend in the biopharmaceutical industry.

Immunoconjugates and bispecific antibodies: Trends in therapeutic success and commercial focus.

Monoclonal antibodies (mAbs) have revolutionized the selective targeting of disease, as well as changing the character of the pharmaceutical industry. Although most attention has focused on conventional antibodies, immunoconjugates and bispecific antibodies (bsAbs) are beginning to show greater potential. Herein, we identify trends in the development and approval of antibody derivatives, as well as the organizations developing these products. Whereas industry development of immunoconjugates has grown steadily over four decades, momentum behind bispecific agents has seemingly expanded only recently. Together, our findings suggest that antibody derivatives provide interesting, albeit still speculative, opportunities for targeted interventions.

A Novel Innovation and Entrepreneurship (I&E) Training Program for Biomedical Research Trainees.

PROBLEM: Contemporary science emphasizes efficient translation of scientific discoveries into tangible, innovative products and services to improve human health. Therefore, researchers need skills in innovation and entrepreneurship (I&E) to select which problems to address and bring to market the most promising solutions. Training in this skillset is not currently available to most biomedical research trainees. APPROACH: The Entrepreneurship for Biomedicine (E4B) training program was created to develop biomedical researchers' I&E skills. The program comprises 2 semester-length courses: E4B1 teaches core skills; E4B2 focuses on advanced skills for those interested in pursuing funding for a new venture. In addition to traditional entrepreneurship training, E4B teaches ethics and personal skills such as resilience, communication, and team-building. Each course is delivered online and requires about 4 hours weekly. Program elements include short videos for didactic content; a team-based capstone project; mentorship from experienced entrepreneurs; and a live, virtual pitch presentation. The program is housed at Washington University School of Medicine in St. Louis and is open to pre- and postdoctoral biomedical research trainees and faculty nationwide. OUTCOMES: In 2020, 77 trainees completed E4B1 and 13 went on to complete E4B2. Trainees in both courses were satisfied with learning content and mentorship and would recommend the program to a friend. Pre- and postanalyses demonstrated that trainees' confidence in their knowledge about and ability to perform I&E tasks taught throughout the program increased. Since completion, 4 graduates have received external funding for an innovation and 3 have started a company. NEXT STEPS: E4B is well accepted, and this preliminary evaluation suggests the program is effective. It could serve to support medical school curricula, business competitions, and technology transfer efforts, which are opportunities for future exploration. A more robust evaluation is planned and recruitment will be expanded to increase participation from women and underrepresented populations.

2021 in review: FDA approvals of new medicines.

The year 2021 witnessed a remarkable number of US Food and Drug Administration (FDA) approvals and registered clinical trials. In total, 60 new molecular entities (NMEs) were approved by the FDA, the highest level achieved in the post-Prescription Drug User Fee (PDUFA) era and tied with 2018. Of these NMEs, 49 used the incentives of the Orphan Drug Act or were approved under Priority, Fast-Track, Accelerated, and/or Breakthrough designations. Looking further, the number of registered clinical trials was off its 2020 record peak but well within the 5-year running average. Nonetheless, these remarkable outcomes were tempered by the fact that the rate of industry consolidation and turnover continued apace, reducing the number of organizations involved in the clinical development of new medicines and raising questions about long-term sustainability.

2020 in review: FDA approvals of new medicines.

Amid a global pandemic, the US Food and Drug Administration (FDA) remained relatively active, approving 55novel molecular entities (NMEs) in 2020, the third highest annual rate recorded. Orphan approvals also surged, capturing 60% of NMEs introduced during 2020, as did the number of NMEs approved using a priority review. The pandemic did appear to impact one recent trend, and in a paradoxically encouraging way. Escalating rates of consolidation slowed in 2020, with only 102 companies lost, down by two-thirds over the rate in 2019. This leaves 2000 extant clinical-stage pharmaceutical companies. When limiting this analysis to companies contributing to the research and development (R&D) of an approved drug, eight were lost, leaving 144 extant.

Sources of innovation for new medicines: questions of sustainability.

The biopharmaceutical industry has undergone remarkable changes over the past half century, driven largely by a need to offset the ever-rising costs of developing new medicines. In this report, we aggregated information about the creation and fate of all clinical-stage biopharmaceutical companies, assessing trends over time. These results reveal that the rate of new company formation has been declining at the same time that industry consolidation has been accelerating at an unprecedented rate. Consequently, the number of companies involved in biopharmaceutical research and development has declined by one-third over the past decade, while those able to achieve at least one FDA approval has dropped by more than half. These findings raise important questions about the sustainability of an industry that is vital for both public and economic health.

Oh, the Frustration of Antibodies!

The COVID-19 pandemic has been humbling for the biomedical community, pointing out as much about what we do not know as what we do. Among these learnings are lessons about immune-based measures to prevent or treat a new biothreat. This article summarizes lessons learned from two experimental approaches for passive immunity, convalescent plasma and monoclonal antibody therapy. Two early reports of outcomes, both of which appeared within hours of one another, reveal the importance of blending past learning with a forward-looking approach. These also present cautionary lessons as the world looks to new vaccines to help eradicate this deadly scourge.

2019 in review: FDA approvals of new medicines.

The US Food and Drug Administration (FDA) green-lighted the marketing of 53 therapeutic agents in 2019. This rate of approvals was consistent with the 5-year running average. Nonetheless, a few changes are worth noting. The rate of medicines first approved using an orphan drug designation declined from 56% in 2018 to 41% in 2019, which mirrored a comparable decline in the use of priority review. A second notable feature was an uptick in industry consolidation. Twenty-five companies were lost, primarily because of mergers, leaving only 146 extant companies that have contributed to the research or development of an innovative FDA-approved medicine.

Expanding roles for academic entrepreneurship in drug discovery.

An assessment of inventors of US Food and Drug Administration (FDA)-approved medicines reveals a growing role for academic entrepreneurship in general and National Institutes of Health (NIH)-supported investigators in particular. For all small-molecule therapeutics approved between 2001 and 2019 (383 in total), 8.3% listed an academic inventor in the Orange Book. Remarkably, an additional 23.8% listed an inventor from a company founded by an NIH-funded academic inventor. Over time, the relative inventive contributions from academia has progressively increased, including nearly one-third of medicines approved since 2017. These findings suggest a surging role for academic inventors and founders, perhaps in combination with a faltering of traditional private sector dominance of drug discovery.

Rising Academic Contributions to Drug Development: Evidence of Vigor or Trauma?

We analyzed therapeutic areas most commonly targeted by academia since 2001, finding a domination of certain oncology and infectious diseases. These findings raise important questions about whether this trend reflects an expanded opportunity arising from academic research or a troubling sign of an industry struggling with the challenges of innovation.

CDEK: Clinical Drug Experience Knowledgebase.

The Clinical Drug Experience Knowledgebase (CDEK) is a database and web platform of active pharmaceutical ingredients with evidence of clinical testing as well as the organizations involved in their research and development. CDEK was curated by disambiguating intervention and organization names from ClinicalTrials.gov and cross-referencing these entries with other prominent drug databases. Approximately 43% of active pharmaceutical ingredients in the CDEK database were sourced from ClinicalTrials.gov and cannot be found in any other prominent compound-oriented database. The contents of CDEK are structured around three pillars: active pharmaceutical ingredients (n = 22 292), clinical trials (n = 127 223) and organizations (n = 24 728). The envisioned use of the CDEK is to support the investigation of many aspects of drug development, including discovery, repurposing opportunities, chemo- and bio-informatics, clinical and translational research and regulatory sciences.

2018 in review: FDA approvals of new molecular entities.

2018 was a remarkable year, both in terms of the number of new molecular entities (NMEs) approved and the organizations developing them. In total, 59 NMEs received a nod from the US Food and Drug Administration (FDA), most of which were approved using a priority or breakthrough designation. Orphan drugs accounted for more than half of new approvals, only the second time in history that level has been achieved. Moreover, the net number of organizations that received an FDA approval and remain active in new drug research surged in 2018, reflecting both an increase in new organizations and lower levels of industry consolidation.