Elizabeth Sukkar is a freelance journalist based in London.
Put simply, if the antibiotics divisions of GSK or AstraZeneca to pick two that kept going had been separate independent discovery companies, they would have been the largest things in the field. And they would have gone bankrupt. Years of work in both shops led to no marketed drugs — the money flowed out constantly and nothing ever flowed back in.
The Pew roadmap sums up the situation this way: New discoveries dropped precipitously from the s onward. As a result, the development of antibiotics has declined, with new Food and Drug Administration FDA approvals for these drugs falling from 29 during the s to nine in the first decade of the s.
All antibiotics approved for use in patients today are derived from a limited number of types, or classes, of antibiotics that were discovered by the mids Figure 1. This is even more concerning than the decline of drug approvals because resistance to one antibiotic often leads to resistance to multiple antibiotics within the same class.
While drugs can be categorized or classified in a variety of ways, for the purposes of this document, antibiotic classes are based on similarities in chemical structure.
Faced with poor discovery prospects and diminishing returns on investment, major drug companies have cut back or pulled out of antibiotic research altogether. Most industry antibiotic development programs are primarily focused on modifying existing classes of drugs discovered decades ago to circumvent bacterial resistance and better target difficult-to-treat infections.
Though essential, such incremental advances are not likely to meet the looming public health challenge of antibiotic resistance in the long term.
The plan calls for efforts to produce new chemical matter in the property space that antibiotics tend to occupy, which is a rather weird one compared to most other drugs and not well served by current screening libraries: It is important to clarify that this proposed effort is not focused on broad expansion of synthetic libraries or seeking out new sources of natural products.
Instead, the goal is to execute focused work to carefully vet existing chemical matter and conduct targeted synthesis and modification of new chemical matter based on what is known about antibacterials from published and unpublished sources, incorporating insights and guidance as new research findings emerge.
It will take time to determine whether conditional guidelines can be developed for Gram-negative drug entry and efflux avoidance. Meanwhile, practical and transparent knowledge-sharing mechanisms should be established to better inform discovery scientists on how to identify new chemical matter based on drug-like qualities and what is already known about the chemical properties of antibiotics.
This would require collaborative research to facilitate new and directed approaches to generate and modify chemical matter. For example, working together across multiple disciplines, scientists may begin to develop new semi-synthetic antibiotic templates derived from fragment-based or natural products-based starting points that better target Gram-negative or Gram- positive bacteria.
To that first point: Antibiotic discovery has a long history, but much of the published research is buried in old journal issues or out-of-print books, and other research never makes it to publication.
Organizing this body of research and making it accessible to the scientists who need it is critical for advancing discovery. Valuable knowledge may include compilations of screens that have been run before and information on past research programs.
While much of this information is publicly available, what may be most useful is an account of what projects failed, and why. Outside of these traditional antibiotic ideas, the document also has a section for working on some of the less standard ones: There are a lot of areas that have seen work on and off the polymyxin membrane-disrupting compounds, iron-uptake pathways as a route to drug entrythat need a more concerted effort.Jan 18, · In a new report, the World Economic Forum (WEF) throws its weight behind the push for 'pull' incentives for the development of new antibiotics, which aim to ensure that drugs that reach the market will be profitable.
Barry Eisenstein, senior vice-president, scientific affairs editor, antimicrobial agents and chemotherapy, for Cubist Pharmaceuticals, and speaking on behalf of EFPIA, says: “The development paradox is that one needs a large number of patients with those infections to develop new antibiotics, obviating the ability to have therapeutic solutions available in time for the epidemic.
To address a major drought in antibiotic discovery, lawmakers have given pharmaceutical companies incentives to research and design new drugs to fight deadly bacteria. Jan 18, · In a new report, the World Economic Forum (WEF) throws its weight behind the push for 'pull' incentives for the development of new antibiotics, which aim to ensure that drugs that reach the market will be profitable.
“Intelligent pull incentives, such as advance commitments and prizes, provide financial rewards to the developer that are not based on the volume of use of the novel antibiotic. With the right set-up, pharma companies will have no incentive to drive use.
Although society wants pharmaceutical companies to research and develop new antibiotics, policy-makers do not want healthcare professionals to use them. In other words, products should sit on the shelf until they are really needed by patients because of the antimicrobial resistance problem through the imprudent use of antibiotics over the years.