They claim an estimated 25,000 lives each year in the European Union alone. And that number could rise dramatically unless better drugs are developed. Pathogens that are resistant to standard antibiotics are a growing threat to global health.
Politicians are pushing for stronger prevention efforts and a new burst of innovation in antibiotic development. The health ministers of the G20 nations, who met in Berlin over the weekend, warned that “progress in the research and development of new antibiotic therapies against life-threatening and highly resistant organisms is slowly drying up.”
They advocate greater financial support for new research initiatives and alliances between industry and universities.
Experts in the pharmaceutical and biotech industries welcome the fresh political will, but warn against hoping for quick results. The battle against bacteria is a tough one to win – mainly because of past omissions. Essential research has been neglected for far too long.
Holger Zimmerman, head of Aicuris, a biotech specializing in anti-infective agents, does recognize a certain trend reversal and is cautiously optimistic. “But the important thing is that what’s now on paper actually becomes reality. We need ongoing support in this area. Otherwise it will go up in smoke.”
The German Association of Research-based Pharmaceutical Companies (VfA) agrees. It sees the G20 statement as groundbreaking, but also believes further action is needed. According to VfA Managing Director Birgit Fischer, activity in the areas of epidemic vaccines and antibiotics must be “significantly expanded, so that the world community can effectively cope with future health crises.”
The problem of antibiotic resistance is an indirect result of the research successes of the last century. In the 1980s and 90s, pharmaceutical companies introduced more than 40 new drugs onto the market, including many broad-spectrum antibiotics that are effective against a large number of bacteria. These drugs are now produced in huge quantities, available for a few cents, and widely used in human and veterinary medicine. That in turn promotes resistance.
At the same time, there is very little commercial incentive to develop new antibiotics. The dilemma pharmaceutical companies face is that failure rates in antibiotic research are similar to those with other drugs, whereas the market potential compared to drugs that treat chronic diseases like cancer remains very modest. It makes sense that to prevent resistance, new antibiotics should only be used very restrictedly. In routine use, however, they have to compete against successful and extremely inexpensive older products.
According to data from Quintiles IMS Health, antibiotics, with about $38 billion, or €34 billion, in sales, are still among the 10 largest therapy classes in the global pharmaceutical market, although sales have been declining since 2013. The market is now almost completely in the hands of generic manufacturers, which perform no research.
Starting in the late 1990s, the major pharmaceutical companies largely abandoned antibiotic research to focus on more lucrative areas, such as cancer and diabetes therapy, as well as autoimmune diseases.
The three leading German drug makers, Bayer, Boehringer and the Darmstadt-based Merck Group, are also no longer active in antibiotic research and, according to their own statements, have no plans to become involved in the field. Bayer spun off its anti-infective agent research 10 years ago into Aicuris, which is heavily funded by former Hexal owners Andreas and Thomas Strüngmann.
“The important thing is that what's now on paper actually becomes reality. We need ongoing support in this area. Otherwise it will go up in smoke.”
However, with growing research funding, there appears to be at least an uptick in activity. Several large pharmaceutical companies signed an appeal in Davos in early 2016, calling for concerted action against antibiotic resistance. And according to industry expert Marc Gitzinger, the number of smaller biotech companies in the field is growing again. Mr. Gitzinger heads Bioversys, a biotech firm based in Basel, Switzerland. He is also the deputy chairman of the Beam Alliance, a group of around 40 smaller pharmaceutical and biotech companies involved in antibiotic research.
The Boston Consulting Group estimates that $500 million in grant funding for antibiotic research is now being provided annually, in the context of international and national initiatives.
In a public-private partnership, the European Commission and the pharmaceutical industry launched the New Drugs 4 Bad Bugs research program in 2012. The seven-year program has received about €700 million in funding. And in 2016, the World Health Organization (WHO) launched The Global Antibiotic Research & Development Partnership, or GARDP. Participating companies agree to supply successfully developed antibiotics to emerging and developing countries under special conditions.
But experts believe further incentives are needed, in addition to direct research funding. “We need to create a certain amount of investment certainty,” Aversys CEO Gitzinger said. “The chain has to work credibly again, or else the initiatives will come to nothing.”
In a study for the German health ministry, experts at BCG propose, among other things, a bonus of $1 billion for the market entry of an urgently needed antibiotic – a model that industry representatives welcome but is also seen as difficult to implement.
New approvals are on the rise, however. The VfA counts 11 new antibiotics since 2011, including drugs to treat tuberculosis and the hospital bacterium MRSA. The association estimates that the number of new antibiotics could grow to 18 by the end of the decade.
A tentative renaissance of antibiotic activities is also taking shape among Big Pharma, with companies like Roche and French drug maker Sanofi boosting their activities in the field. In 2014, Sanofi began an alliance with the Fraunhofer Institute, contributing its extensive collection of naturally occurring substances. US producer Merck & Co. (which has no relationship with the German Merck Group) expanded in 2014 with the acquisition of biotech company Cubist, including its bestselling drug Cubicin. Industry leader Pfizer recently acquired the antibiotics division of AstraZeneca.
However, the companies were mainly interested in current business and development products that were almost ready for market. In both cases, basic research was scaled back or spun off. Experts see this as particularly troubling given the lack of new approaches to fighting pathogens. And most of the roughly four dozen projects currently in clinical development are based on known substance classes.
New mechanisms are needed, especially to confront the problem of resistance. “To keep resistance at bay in the longer term, we need a lot more drugs with novel mechanisms of action, with which the pathogens are not yet familiar,” Aicuris CEO Zimmermann warned. “This is difficult but ultimately it needs to be rewarded.”
Handelsblatt’s Meike Telgheder covers the pharma industry; Siegfried Hoffman also writes about the pharma and chemicals sectors. To contact the authors: firstname.lastname@example.org, email@example.com