The development of new antibiotics yields so little that the world has become highly dependent on a group of small and medium-sized companies that are often in bad financial shape. Some of them are seeking collaboration with Chinese parties to spread risks and avoid bankruptcy, non-profit research organization Access to Medicine Foundation (ATMF) reported Thursday.
While the corona outbreak has not yet been contained worldwide, microbiologists are increasingly warning about what they call a ‘silent pandemic’: the rapidly increasing resistance of pathogenic fungi and bacteria to antibiotics. An estimated 700,000 people, mainly children and the elderly, die each year from infectious diseases such as blood poisoning, pneumonia and tuberculosis caused by resistant pathogens. Most of the victims are in low- and middle-income countries.
The United Nations wrote two years ago that their number could rise to more than 10 million deaths a year over the next three decades if global action is not taken quickly. That is slightly more than the annual death from cancer, while Covid-19 has so far caused 3.75 million victims worldwide, according to official statistics. In addition, effective antibiotics are necessary for safe surgery and for new treatments for several serious conditions, including cancer.
“Although history tells us that there is one pandemic every 100 years, the next is already a fact,” Plymouth University of Microbiology professor Tina Joshi concluded recently in the British magazine The New Statesman. According to Joshi and other experts, resistant pathogens, along with climate change, pose the greatest threat to public health.
Indispensable in the fight against advancing resistance of bacteria are new, innovative forms of antibiotics. But they are underdeveloped. The pipeline is “virtually static,” the World Health Organization recently wrote . Only a handful of new antibiotics have entered the market in recent years. Most of them (82 percent) are derivatives of existing drugs to which some strains of bacteria have already built up resistance. The expectation is that the same will happen with the modified variants in the foreseeable future.
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The development of new antibiotics is costly and risky, while expected returns upon success are modest at best. Margins on antibiotics are relatively low. More importantly, in order to prevent rapid resistance, it is necessary to distribute antibiotics in a highly targeted and limited quantity, followed by close monitoring of use and emerging resistance. It is precisely the excessive and ‘careless’ use of antibiotics, in both humans and animals, that encourages resistance. “Companies often get neither the margin nor the volume,” sums up ATMF director Jayasree Iyer.
That is why many large pharmaceutical companies have withdrawn from research into new antibiotics. Innovation should mainly come from smaller companies. These now account for three quarters of the upcoming experimental antibiotics, calculated the ATMF, a British and Dutch government-funded organization that investigates what pharmaceutical companies do to make medicines available to people in poor(er) countries.
According to the researchers, most smaller companies that develop antibiotics struggle to survive. Governments and philanthropic organizations usually help fund the early stages of research. In addition, here and there, including in the United Kingdom, experiments are underway with new methods of rewarding innovation. Consider a subscription model in which governments are given access to (various) antibiotics against periodic payment.
Hopeful initiatives, Iyer says, but far too few to ‘fix’ the market. Especially in later research phases, many antibiotic developers are at risk of collapse. Or they really go bankrupt, like the American biotech companies Aradigm and Achaogen, even if the results are good or drugs have already been approved. It’s what Iyer calls the “R&D Valley of Death.”
Still, some relatively small antibiotic developers manage to survive. Remarkably often, this is due to cooperation with Chinese parties, the ATMF discovered. They are responsible for part of the development and later distribution and commercialization of the antibiotic. According to Iyer, the explanation for this is that resistance of bacteria is relatively common in China and that there are therefore many patients for research.
A version of this article also appeared in NRC Handelsblad on 10 June 2021
A version of this article also appeared in NRC in the morning of June 10, 2021