Antibiotics: Reconciling profit and sustainable use

Companies should be rewarded for developing antibiotics. But only if – at least for a certain time – a new drug remains robust in the face of bacterial resistance.

By rewarding the long-term effectiveness of antibiotics, the profit motives of pharmaceutical companies can be reconciled with the sustainable use of these drugs. The idea of a group of researchers at the University of Geneva, working together with Swedish and Canadian colleagues, is convincingly simple. But the economic reality in antibiotic research and development isn’t. Antibiotics are cheap compared to other drugs, but their development costs the same – if not more.

That’s why large financial incentives to accelerate antibiotic research and development, such as market entry rewards, are being considered by governments around the world. “But at the same time, we need to restrict the use of potential new drugs in order to prevent the development of bacterial resistance”, says Chantal Morel, health economist at the University of Geneva, “and this again diminishes the prospects for profits”.

Good performance increases the reward

To resolve this contradiction, Morel and her colleagues propose adding a performance component to any scheme that rewards the results of antibiotic development on a large scale. By way of comparison, the UK government’s Antimicrobial Resistance (AMR) review group has proposed a reward as high as USD 1.6 bn for bringing an antibiotic to market. With a performance component, this reward could be split: a company would receive a fixed sum of USD 1bn at the time of market approval plus conditional payments at years 5, 10, 15 and 20, depending on whether the product maintains its effectiveness.

This approach has the real strength of being able (at least partially) to decouple the profitability of developing a new antibiotic from the volume sold. The expected benefits are two-fold, as Morel explains: “First, companies would be incentivised to promote antibiotics less aggressively in order to avoid overuse. Second, firms would from the outset be guided towards real innovation – i.e. towards advancing candidate products that show the greatest likelihood of long-lasting effectiveness”.

It’s time to fix the details

The discussion about market entry rewards, with or without a performance component, has been going on for several years. So far, however, governments have not made any binding commitments. This makes it very difficult to win over companies to support these schemes. In talks with firms’ representatives, Chantal Morel has obtained a clear response: “As long as the rewards are so vague, private companies won’t invest”, she says. And while a performance component might be interesting for them, its exact mechanisms have to be defined in binding terms. That’s what Chantal Morel and her colleagues are working on at the moment. Two key aspects need to be addressed: How big should the bonus be? And how will the effectiveness of a drug be measured over time?

How much exactly?

“To sufficiently incentivise the industry, the bonus must exceed the profits it is foregoing through the constraints on its business, while at the same time respecting taxpayers or other funders of the scheme”, says Chantal Morel. The researchers are navigating those divergent interests in a close dialogue with decision-makers from government agencies and industry, mainly in European countries. They are also elaborating proposals that should deter companies from not selling drugs at all in certain countries just to secure the bonus. One solution would be for drug companies seeking the bonus to agree to provide their product when requested by qualifying buyers who meet the requirements for responsible use. “Supply would thus be triggered by justified requests for the product rather than by the companies’ promotional activities”, Morel explains.

Measuring the effectiveness of drugs

At the heart of the proposed mechanism is the drug’s effectiveness over time. This in general is defined by the amount of an active ingredient that is needed to inhibit the targeted pathogenic bacteria. At present, such data is not routinely gathered on a large scale for new antibiotics. In fact, the surveillance of antibiotic resistance has until now been focused on a small number of infections and pathogens and on a limited number of older antibiotics. Furthermore, it is mostly done in high-income countries.

However, new surveillance methods are developing quickly, and these will allow us to gain a more accurate, comprehensive and up-to-date picture of the situation. Nevertheless, all involved parties need to agree on thresholds for precisely determining when a drug’s overall efficacy – or lack of efficacy – has been established.

Who will take the first step? Pioneers welcome!

Chantal Morel and her team can show exactly how the system would work and what it would need – and that it would be a win-win situation for everyone. But to establish it, a large number of actors will have to work together, from governments to companies to scientists. Ideally, market-entry rewards with a performance component would be organised on an international basis, as Chantal Morel says. But as is so often the case, it is individual countries that must take the first step. At present, the UK and Sweden are outstanding examples of countries seriously discussing novel schemes to re-ignite antibiotic research and development. But for Chantal Morel it’s clear that Switzerland should also take a leading role here: “Switzerland not only has the necessary resources, it is also home to a strong research-based industry. That puts it in an ideal position to do pioneering work in this area”.