The discovery of the first antibiotic, penicillin, over 90 years ago, has revolutionised modern medicine. Since then, antibiotics have become one of the most common classes of drugs – used to prevent and treat infections, and make possible complex surgeries that have become routine, from caesarean sections to hip replacement surgeries and organ transplants.
But antibiotics are not as effective as they used to be. Over time certain bacteria, so-called ‘superbugs’, have adapted and learned to resist the effects of the drugs designed to kill them. Our collective overuse of antibiotics – in humans, animals and plants – has accelerated this process.
Today, drug-resistant infections are a serious threat to people’s health. Hundreds of thousands of lives are lost every year because of infections that can no longer be treated with existing drugs. Discovering new antibiotics, able to kill drug-resistant bacteria, is essential to saving modern medicine.
But that’s only part of the solution, as over time bacteria will learn to resist the new drugs too. To stay ahead of the game in this constant race against superbugs, we also need innovations in developing vaccines and diagnostics, and better prevention control and surveillance.
No new classes of antibiotics have been discovered since the 1980s. A class defines a group of antibiotics that have a certain way of working – for example by killing bacteria or by stopping them multiplying – and are effective against certain types of infections.
The antibiotics that have been brought to market in the past three decades are variations of drugs that have been discovered before.
Discovering and developing genuinely new antibiotics is challenging: the science is tricky and the research and development process is time-consuming and expensive, and often fails.
It can take 10-15 years and over $1billion to develop a new antibiotic.
Stages of antibiotic research and development (R&D)
The current economic model for developing new antibiotics is failing. Companies invest huge amounts of money to bring a new drug to market but cannot recover their costs or make a profit.
"This is the only field within pharmaceutical science where you come out with a drug and you don’t want it to be used too much," explained Anand Anandkumar, CEO of Bugworks, a biopharma start-up dedicated to discovering new antibiotics.
New antibiotics are seen as ‘drugs of last resort’ against dangerous bacteria. So, to limit the development of antibiotic resistance, they need to be used sparingly – and not sold in large volumes. Plus, compared to more expensive treatments, antibiotics tend to be quite low in price.
The combination of low sales and low prices limits the amount of money companies can make. Without financial incentives, many large pharmaceutical companies have started to pull out of the field. In the 1980s there were 18 multinational companies committed to antibiotic research; today there are only a handful.
Antibiotic R&D is now primarily driven by small biotechnology companies. In recent years, they have made some exciting scientific breakthroughs.
Many have been funded through initiatives such as CARB-X – a partnership between governments and philanthropic organisations like Wellcome – through what is called ‘push’ funding.
A scientific breakthrough doesn’t guarantee success though, as much more funding is needed to see drugs through the expensive process of clinical trials, registration and coming to market. Once companies lose early-stage funding, it becomes much more difficult to find investment.
The question of how to make antibiotic research and development sustainable remains.
At the moment, there aren’t sufficient drugs in development to deal with the growing threat of antibiotic resistance.
According to the World Health Organization and the Pew Charitable Trust, there are currently between 40 and 50 antibiotics in clinical development. Many of these will only bring limited benefits compared to existing treatments. And only a few target Gram-negative bacteria, which are the most dangerous resistant bacteria and can cause severe infections like pneumonia, bloodstream infections or meningitis.
The pre-clinical pipeline includes more innovative and diverse candidates – over 250 antimicrobial agents are in early-stage testing. But it will take up to 10 years for the first of these drugs to make it to market.
And many promising candidates will fail along the way. For antibiotics in existing classes, on average, only one for every 15 drugs in pre-clinical development will reach patients. For new classes of antibiotics, only one for every 30 candidates.
With large pharmaceutical companies continuing to abandon antibiotic research, small and medium-sized companies now dominate the space – they account for around 90 percent of the new antibiotics in development. But they face formidable challenges in trying to bring new drugs to market and making them accessible.
Innovation also comes from not-for-profit organisations – pretomanid, which was recently approved for patients with highly drug-resistant forms of tuberculosis, was developed by TB Alliance.
While non-traditional development pathways are valuable, strengthening the antibiotic pipeline requires ambitious solutions to retain and attract new investment into antibiotic R&D.
Industry, governments and philanthropic organisations need to work together to ensure a sustainable pipeline of new drugs. There are different options.
One is implementing a system of 'market entry rewards' – giving lump-sum payments to successful developers of new antibiotics, as first suggested in Jim O’Neill’s report.
Another idea is a ‘subscription’ style payment model, which the UK government announced it will be piloting. This involves paying pharmaceutical companies upfront for access to drugs based on their usefulness to the NHS.
Other interventions have proposed treating antibiotics as a global good, for example, by governments stockpiling antibiotics as they do with emergency medicines.
These solutions will require significant investment from governments, and the commitment has been low so far.
Among the pharmaceutical companies that have remained committed to antibiotic R&D, some have started to change their practices, for example by: removing financial bonuses tied to sales, sharing data on the spread of drug-resistant infections and putting plans in place to ensure better access to new antibiotics. While these trends are encouraging, change is not happening at the scale required.
The global community needs to respond quickly to make sure we protect modern medicine against the increasing threat of drug-resistant infections while there is still time.
New partnership models which share risk, resources and expertise across philanthropies, industry and the public sector could provide answers.