Repurposing – second life for drugs

Drug repurposing refers to finding new indications for existing drugs. The paradigm shift from traditional drug discovery to drug repurposing is driven by the fact that new drug pipelines are getting dried up because of mounting Research & Development (R&D) costs, long timeline for new drug development, low success rate for new molecular entities, regulatory hurdles coupled with revenue loss from patent expiry and competition from generics. Anaemic drug pipelines along with increasing demand for newer effective, cheaper, safer drugs and unmet medical needs call for new strategies of drug discovery and, drug repurposing seems to be a promising avenue for such endeavours. Drug repurposing strategies have progressed over years from simple serendipitous observations to more complex computational methods in parallel with our ever-growing knowledge on drugs, diseases, protein targets and signalling pathways but still the knowledge is far from complete. Repurposed drugs too have to face many obstacles, although lesser than new drugs, before being successful.

Innovations and Patent Trends in the Development of USFDA Approved Protein Kinase Inhibitors in the Last Two Decades

Protein kinase inhibitors (PKIs) are important therapeutic agents. As of 31 May 2021, the United States Food and Drug Administration (USFDA) has approved 70 PKIs. Most of the PKIs are employed to treat cancer and inflammatory diseases. Imatinib was the first PKI approved by USFDA in 2001. This review summarizes the compound patents and the essential polymorph patents of the PKIs approved by the USFDA from 2001 to 31 May 2021. The dates on the generic drug availability of the PKIs in the USA market have also been forecasted. It is expected that 19 and 48 PKIs will be genericized by 2025 and 2030, respectively, due to their compound patent expiry. This may reduce the financial toxicity associated with the existing PKIs. There are nearly 535 reported PKs. However, the USFDA approved PKIs target only about 10–15% of the total said PKs. As a result, there are still a large number of unexplored PKs. As the field advances during the next 20 years, one can anticipate that PKIs with many scaffolds, chemotypes, and pharmacophores will be developed.

Practical considerations for creating a strategic and proactive clinical safety and pharmacovigilance organization for the future

OBJECTIVE: In 2012, Patient Safety (PS) in AstraZeneca was facing a situation with multiple challenges, scientifically and structurally. To meet these and support AstraZeneca’s ambition to return to growth after years of patent expiry, we undertook a project to fundamentally revisit ways of working to create an organisation set up to provide strategic safety in support of drug project decision-making. METHOD: In this paper, we describe the challenges we faced, the project to deliver changes to respond to them, and the methodology used. The project had two main components: creating a new operating model and simplifying the procedural framework. RESULTS: It was delivered in a focused effort by internal PS resources with cross-functional input. The framework simplification resulted in a 71% reduction in procedural documents and a survey of PS staff revealed an increase in satisfaction of 10%–20% across all scores. CONCLUSIONS: With >3 years of observation time, this project has provided AstraZeneca with a PS organisation able to provide strategic safety, supporting successful portfolio delivery, while ensuring patient safety and maintaining compliance with global pharmacovigilance regulations. It has driven efficiency and set the foundation for continued organisational evolution to meet future business needs in an everchanging environment.

Authorized Generics and Biosimilars as Part of Drug Life Cycle Management

Nowadays there is no longer a clear distinction between innovative pharmaceutical companies and generic and biosimilar manufacturers. The latter seek patent protection for new formulations or medical uses of known pharmaceuticals, and originators have responded by building their own generic divisions. Through them, innovative pharmaceutical companies are able to launch their own generics or biosimilars to cushion the loss of revenues after the expiry of blockbuster patents. In particular, in recent years so-called authorized generics and biosimilars have received increased attention as part of patent expiry strategies.

Global challenges in the manufacture, regulation and international harmonization of GMP and quality standards for biopharmaceuticals

Biopharmaceuticals belong to a class of medicinal products whose active pharmaceutical ingredient (API) is manufactured using living systems such as microbial and mammalian cells. With the patent expiry of the originator biopharmaceuticals, a surge in the production of biopharmaceuticals in the form of biosimilars is to be expected. However, biopharmaceuticals are inherently more complex than conventional chemical-based pharmaceuticals, hence requiring a more complicated manufacturing process. This paper provides a brief overview of the biopharmaceutical manufacturing processes and reveals that most biopharmaceuticals share similar processes and considerations. The complex nature of biopharmaceuticals presents various manufacturing challenges such as the inherent variation in quality and demand for extensive process and product understanding. Furthermore, downstream processing bottleneck also presents another manufacturing challenge. A brief comparison of the good manufacturing practice (GMP) standards of various regulatory authorities (RAs) and international organizations (IOs) reveals that the standards are largely similar and appropriate in addressing the manufacturing challenges. This review is one of the few covering the biopharmaceutical industry and the regulatory framework of the Association of South East Asian Nations (ASEAN). However, GMP alone does not address regulatory challenges such as evaluation of biosimilarity, differing outlook on interchangeability and a growing occurrence of data integrity lapses. Solutions such as the implementation of Industry 4.0, improved harmonization of regulatory efforts and creating a culture of quality within the organization may help to address the forgoing challenges.

Evaluation of adverse events focusing on infection associated with infliximab originator and biosimilar using a spontaneous reporting system database

Background Infliximab (IFX) has changed the management of many life-threatening immune-mediated diseases. The high cost of IFX and its patent expiry have led to pharmaceutical companies developing a biosimilar; however, its safety profile remains unknown in the real world. The purpose of this study was to clarify the adverse events associated with IFX originator and its biosimilar using the Japanese Adverse Drug Event Report (JADER) database. Methods Adverse event reports submitted to the Pharmaceuticals and Medical Devices Agency between the third quarter of 2014 and the fourth quarter of 2018. We calculated the reporting odds ratio and 95% confidence interval for each adverse event. Results We obtained 2771 reports of adverse events associated with IFX originator and 402 reports with IFX biosimilar. Signals were detected for pneumonia, interstitial lung disease, tuberculosis, and sepsis with both IFX originator and its biosimilar, whereas there was no signal for infection with the biosimilar. Conclusions The strength of the association between IFX originator and its biosimilar with adverse events is partly different, but reports were quite limited for the biosimilar compared with originator. It is recommended that research be continued in order to accumulate a wide variety of information, and that newly reported data be placed in the multifaceted viewpoints for improvement of care levels.