Is the pharmaceutical industry’s preoccupation with the monotherapy drug model stifling the development of effective new drug therapies?

Abstract

Drug discovery and development is heavily biased towards the development of monotherapies. Screening, testing, and evaluation of mono-entity drugs are generally much simpler than drug combinations, and are generally easier to get approval from the regulatory authorities for their clinical use. However, monotherapy drugs may not have optimal activity, may have associated toxicities, or may lose activity over time as their target develops resistance. Drug combinations, often developed from existing monotherapies, may have improved efficacy and/or be less toxic. Furthermore, the existing drugs which have lost efficacy due to the development of resistance can often be re-activated by combining them with other chemical entities. Thus, whilst the current climate for drug approval, registration, and clinical use drives the majority of drug development research towards the development of monotherapies, combinations are often a substantial improvement on the original drug. This commentary examines monotherapy and combinational therapy models and discusses the benefits and limitations of each model.

From Petri Dish to Patient: Bioavailability Estimation and Mechanism of Action for Antimicrobial and Immunomodulatory Natural Products

“…It could be argued that the modern techniques of molecular docking and rational drug design have demonstrated little success by comparison with the much less sophisticated screening methods employed during the ‘golden era’ of antibiotic discovery and this gives impetus to calls for a new iteration of natural product screening in the search for new efficacious drugs and novel drug scaffolds (Lyddiard et al, 2016). Yet another lesson we could learn from the ‘dark age,’ and Fleming’s grim yet accurate prediction, is to direct research efforts toward development of combination therapy drugs, by contrast with the monotherapy drug approach that ushered in the resistance paradigm (Cock, 2018).…”

“…If this is indeed true, then the trade-off may be that with higher specificity and potency comes greater probability of resistance development. Adjuvants can, in some cases, disrupt resistance mechanisms (Cock, 2018), but combination therapies that target two or more sites provide arguably the best strategy for preventing further resistance development. Thus, this new paradigm of dual-therapy drugs opens a potential niche for the common non-specific antimicrobials found in natural product research that could be used to complement the conventional antibiotics that are losing potency in the unrelenting march of microbial resistance.…”

Empirical Study on the Transparency of Security Risk Information in Chinese Listed Pharmaceutical Enterprises Based on the ANP-DS Method

“…From the "Plum Blossom K" and "Guan Mu Tong" incidents to the Changchun Changsheng vaccine incident, these occurrences cause widespread concern for the pharmaceutical industry [1,2] and seriously threaten the public's health and safety [3,4], thereby affecting government credibility and social harmony and stability [5,6]. Chen [7], Uthayakumar and Priyan [8], and de Korne et al [9] believed that, as a field closely related to people's lives, health, and safety, medicines have a security risk in any part of the production, transportation, storage, and usage.…”

Epigenetic treatment of dermatologic disorders

“…Thus, reshaping the microbiome (Gilbert et al, ) by modifying the genetic diversity of the various commensal bacterial compositions towards a healthier state, especially on skin (Blume‐Peytavi et al, ; Knight et al, ; McCoy et al, ; Rocha & Bagatin, ; Vollmer, West, & Lephart, ), and/or harnessing them to produce bioactive therapeutic products, including those influencing gene expression, present opportunities for therapeutic intervention (Bueso, Lehouritis, & Tangney, ; Dietert & Dietert, ; Eisenstein, ; O'Neill & Gallo, ). Indeed, therapeutic epigenetic regulation—nongenetic influences on gene expression (changes in phenotype that do not involve alterations in the genomic DNA sequence)—loosely defined as environmentally induced biological processes that silence, activate, and/or modulate gene expression pathways is increasingly garnering clinical recognition (Berson, Nativio, Berger, & Bonini, ; Cock, ; Feinberg, ; Jadotte, ; Kang, Chovatiya, & Tumbar, ; Mervis & McGee, ; Yamatsugu, Kawashima, & Kanai, ).…”

“…Indeed, therapeutic epigenetic regulation-nongenetic influences on gene expression (changes in phenotype that do not involve alterations in the genomic DNA sequence)-loosely defined as environmentally induced biological processes that silence, activate, and/or modulate gene expression pathways is increasingly garnering clinical recognition (Berson, Nativio, Berger, & Bonini, 2018;Cock, 2018;Feinberg, 2018;Jadotte, 2019;Kang, Chovatiya, & Tumbar, 2019;Mervis & McGee, 2019;Yamatsugu, Kawashima, & Kanai, 2018).…”