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.

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.

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.

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.

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.

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.

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.

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.