Why is big Pharma getting out of antibacterial drug discovery?

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Abstract

Since the advent of the antibiotic era in the late 1940s drug discovery and development has evolved into an expensive, time consuming, cumbersome and bureaucratic process involving multiple interest groups such as pharmaceutical manufacturers, governmental regulatory authorities, patent officers, academic and clinical researchers and trial lawyers. It would seem that the least involved among the interest groups are the consumers of health care themselves. Politicians and the public alike complain loudly about drug prices although fewer and fewer new therapies are being developed. The cost and complexities of drug discovery and development have shifted the investment equation away from the development of drugs targeting short course therapies for acute diseases and towards long-term treatment of chronic conditions. Coupled with the failure of large investments into target-based approaches to produce novel antibacterial agents, companies large and small have exited from this field despite a growing clinical need.

Introduction

There is an easy and accurate answer to the question posed in the title: it is the prevailing view in Big Pharma that there are better ways to invest research dollars. Therefore in the past four years Aventis, Bristol-Myers Squibb, Eli Lilly, Glaxo SmithKline, Proctor and Gamble, Roche, and Wyeth have greatly curtailed, wholly eliminated or spun off their antibacterial research. This reversed a trend in the early 1990s where large companies restarted antibacterial research to address the emergence of antibacterial drug resistance.

Section snippets

Is there actually a need for novel antibacterial drugs?

While it is true that infectious diseases are the second leading cause of death worldwide and the third leading cause of death in developed countries [1], the main rationale for the development of novel antibacterial agents is the emergence and dissemination of resistant strains. In fact, it has been difficult to demonstrate that patients infected with resistant bacteria have poorer clinical outcomes than patients infected with susceptible bacteria and this is especially true when other

The antibacterial market has lost its attractiveness

Even though the number of doses of antibacterials used has continued to increase annually, the market size (in dollars) has remained flat; predictions of market growth to $32 billion by 2010 not withstanding. There are clear market pressures that are likely to result in lower revenues. These include the availability of generic forms of two of the largest selling or most widely used antibiotics: amoxacillin/clavulanate (Augmentin) and ciprofloxacin (Cipro). In addition, there has been increasing

Portfolio optimization

Pharmaceutical companies invest large amounts of capital to discover and develop novel therapies. While this investment actually surpasses the total budget for the National Institutes of Health (NIH) it is still finite and, just like the extramural funding of basic research by NIH, many worthy, even valuable projects cannot be supported. In the case of pharmaceutical companies, various competing projects must be prioritized relative to each other and a key parameter used in that prioritization

Antibacterial research, particularly target-based approaches, has not been productive

Although many infectious disease groups at large pharmaceutical companies are, or were, far from the largest in their respective organizations there has still been a considerable amount of resources that were devoted to the discovery of novel antibacterial agents. Yet very few novel antibacterial agents have made it as far as clinical development. The explosion of genomic data has not delivered the promised ‘flood’ of novel targets — rather focusing efforts back on the tried and tested [7].

Drug approval is becoming increasingly problematic

Regulatory authorities have come under increasing public and government scrutiny particularly in making pronouncements or decisions regarding the safety of novel agents in all therapeutic areas. In the anti-infective arena, the example of trovafloxacin is often cited in which infrequent hepatotoxicity was not observed until after the drug was widely marketed [9]. In addition to safety, regulators both in Europe and the United States have been demanding demonstrations of relative efficacy within

Solutions and conclusions

Almost all of the solutions proposed below call for changes in public/social policy and are going to come at some cost. Quite simply, if we want new therapies then someone is going to have to pay for it. However, one critical item that does not cost anything is a change in cultural outlook: we need a culture of cooperation between stakeholders; one that recognizes that there must be a balance between public health/clinical needs and the commercial realities of drug discovery and development.

References and recommended reading

Papers of particular interest, published within the annual period of review, have been highlighted as:

  • •

    of special interest

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    of outstanding interest

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