May 5, 2014, by James Smith

Novel Antibiotics: Is enough being done?

It is well documented in the media and literature that current antibiotics available on the market are losing their effectiveness against bacterial infections due to bacterial resistance. However, there is little coverage on what is being done to find novel antibiotics and this raises the question; is enough being done to discover new antibiotics?

Many newspapers have covered the ‘antibiotics crisis’ with some claiming that within 20 years all the antibiotics currently in our pharmacies will be ineffective and that untreatable ‘superbugs’ will wipe out humanity. Although these claims may be dramatised, designed to induce a public frenzy, many health organisations agree with the severity of the problem. For example, the World Health Organization (WHO) claims that “antibiotic resistance is becoming a public health emergency of yet unknown proportions”. Hence, there is a general consensus that developing novel antibiotics should be a priority for the pharmaceutical industry.

What are the issues facing the pharmaceutical industry regarding novel antibiotic development? One issue is that many feel a dead end has been reached with antibiotic discovery, with many companies unsure what types of molecules to test or what direction to head in. Controversial though it is, the pharmaceutical industry has been designed to make money, like any other industry. Many companies are unwilling to invest millions of pounds into research and development if they are not confident of an effective product reaching market, generating profits. On top of this, any product that is marketable is likely to have it’s use restricted to  antibiotic-resistant infections, hence resulting in a low volume of sales. In short, to me it seems that there is a lack of financial incentive for pharmaceutical companies to develop new antibiotics due to the risks of ending up with no marketable or profitable product.

In the USA, the Food and Drug Administration (FDA) recently announced plans to incentivise the development of antibiotics through the Antibiotic Development to Advance Patient Treatment (ADAPT) Act of December 2013. This Act allows new antibiotics to be approved by the FDA, fast-tracking them to the market for the purpose of treating life-threatening infections in select patient groups. It also aims to educate healthcare professionals about the safe use of antibiotics to avoid resistance and ensures that bacterial resistance is monitored closely, with the data generated publicly available to healthcare professionals, academics and hospitals. It builds upon the Generating Antibiotic Incentives Now (GAIN) Act legislated into American law in 2012. This act increases market exclusivity of newly developed antibiotics, provides extra development and documentation guidance from the FDA and aims to fast-track novel antibiotics to market. Arguably, these Acts have helped, with a reported 16 new compounds being developed and eligible to qualify for the benefits that the GAIN Act offers, although admittedly these compounds are still in early development, far from reaching market. These Acts are similar to the Orphan Drug Scheme run by the European Medicines Agency (EMA). The Orphan Drug Scheme aims to incentivise pharmaceutical companies to develop medicines for rarer conditions where there is a smaller patient group (5 in 10,000) and where profits may be scarce. Again, guidance for clinical trials and documentation is provided, as well as reduced fees and increased market exclusivity. If a similar scheme regarding antibiotic development was created by the EMA it may further increase the interest that pharmaceutical companies have in developing new antibiotics, hence increasing the chance of novel antibiotics being discovered and developed.

It is also important to note that a few companies have been forming strategic business partnerships to collaborate in the development of antibiotics. Most notably, Spero Therapeutics recently teamed up with Roche, the Swiss pharmaceutical powerhouse. Spero Therapeutics is a relatively new company specialising in developing antibiotics, bringing in microbiological experts from all over the world to help tackle the issue posed by antibiotic-resistant bacterial infections. The agreement is that Roche invests in Spero’s search for novel antibiotics, with Roche retaining the option to develop any lead compounds at the Investigational New Drug application phase (i.e. just before clinical trials). This combination seems to be promising as Spero therapeutics specialise in antibiotic discovery, ensuring that funds are used effectively by experts in the field, whereas the experience and financial resources of Roche will improve the chances of the lead compound performing through clinical trials and reaching market. More strategic partnerships like this may accelerate the development of promising novel antibiotics.

Furthermore, I recently became aware of an article which claimed the pharmaceutical industry required a reformation process if new medicines are to be discovered. The article, found on Pharma Times ( 24/Creating_a_new_ecosystem_for_drug_discovery.aspx? ), was about Professor Chas Bountra from the University of Oxford who feels the pharmaceutical industry should scrap the patent and intellectual property system in current use. Instead, he argues that pooling resources and research for open access to all the companies will increase the chance of successful medicines being developed and this would certainly help the development of novel antibiotics. I found this to be an interesting concept. A total reform of the pharmaceutical industry may be a huge ask and may not be well received by companies, but the scrapping of patents protecting new chemical entities with promising antibacterial properties may be a reasonable step to take. Having numerous companies working on the development of the same group of molecules may increase the chance of them being formulated into successful and safe medicines.

In addition to all these points, there is not only a need to discover and produce new antibiotics, but also to protect the ones we have currently. As a future health care professional, I already take my role as an antibiotic guardian very seriously; as should all over health care professionals. Antibiotic efficacy can be ruined and resistance can arise due to unnecessary prescribing, or by patient’s not finishing their courses on antibiotics. It is our role to ensure neither of these things happen. On top of this, when a patient’s infection is identified and antibiotics are a necessity, we have a key role to assess the antibiotics prescribed to ensure that they are going to be effective against that species of bacteria. In addition, we should push and campaign for further limitations of usage in agriculture where possible.

Some of these suggestions may seem a bit naive or unrealistic. But there is no doubt that novel antibiotics are required and as the crisis goes on, increasingly radical procedures and ideas are going to have to be considered. To me, the propsect of a post-antibiotic world  springs up images of a post-apocalyptic world, where infections that we have considered minor for the past century or so will have the capacity to kill. That image may be slightly exaggerated (and I certainly don’t see a zombie in sight) but there is no denying that it is a terrifying prospect for humanity.

In conclusion, there are certainly sectors of the Pharmaceutical industry putting in the time and resources into novel antibiotic research. On paper, the pooling of resources, scrapping of intellectual property and more strategic business partnerships may help to increase the rate at which antibiotics are discovered. On top of this, if the EMA were to introduce a scheme for antibiotic discovery, similar to the current Orphan Drug Scheme (or the FDA’s GAIN and ADAPT Acts), then antibiotic development may be incentivised, increasing the time and resources dedicated to their discovery. As for the current and future use of antibiotics, it is the responsibility of pharmacists and other healthcare professionals to ensure they are being used safely and sensibly, a role that should be taken extremely seriously.

Posted in Law and EthicsPharmaceutical Research