Over-prescription of antibiotics has turned common infections into a nightmare for patients and the medical fraternity both. The problem is already recognized in developed countries, but the numbers and effects are yet to be quantified in the developing world, where usage is rampant.
The COVID pandemic has added to the urgency in combating the increasing threat of drug-resistant strains of bacteria. More than 1.3 million people worldwide are dying each year from antibiotic-resistant infections, and it is estimated this number will grow to 10 million per year by 2050, according to The Lancet and WHO.
Big pharma companies are no longer interested in investing in research for new antibiotics, and the FDA has not approved a new antibiotic since 2019. According to a report, seven companies in the research and development of antibiotics have gone bankrupt or left the business altogether.
More than 90 percent of all antibacterial discoveries were made in the first half of the 20th century. There have been only 11 indirect-acting NCEs approved, including seven drugs that work to extend the activity of existing antibiotics. Only one new molecular target (new chemical entity)NCE has been approved over the last 35 years, illustrating a need to speed up the antibacterial discovery space.
The Antibacterial Pipeline
The existing clinical antibacterial pipeline is insufficient to meet the growing threat of antibiotic-resistant pathogens. Only 64 NCEs are in clinical trials out of which 20 are candidates for tuberculosis and Clostridioides difficile. The report says the antibiotic development ecosystem is “fragile and failing.”
“Historic success rates for drug development have shown that the number of shots on goal must increase if we are to see life-saving therapies become available for patients,” the authors of the report wrote.
ROI in Research
Lower return on investments has led drug companies to pull the plug on further research. Antibiotic companies have raised just $0.16 billion in the last decade.(less than what they raised 10 years prior). The report estimates that smaller companies are engaged in R&D of nearly 81% of the antibiotics currently in the clinical pipeline.
Of the 12 antibiotics companies that have gone public in the past decade, only five are actively in the business. One company (Achaogen) went bankrupt within a year of gaining a new antibiotic approval.
“When you have companies that reach FDA approval after 20 years of R&D and then go bankrupt, the problem must be the market,” said David Thomas, vice president of industry research at BIO and an author of the report.
Another report released by the Boston Consulting Group (BCG), in partnership with the Wellcome Trust, the World Economic Forum, and the Novo Nordisk Foundation points out the lack of innovation in this space. It reveals that whatever antibiotics have been approved in recent years aren’t all that different from previously approved antibiotics.
“But incremental changes in new antibiotics fail to stop the development of resistance, and the pipeline of truly novel drugs in development or coming to market has dried up,” the BCG report states.
There is a lack of dedicated marketing and interest in extending availability across the globe. Of the 18 antibiotics approved in the United States, the European Union, Canada, and Japan since 2010, many have not even been launched in major markets and are unavailable in most countries.
Future of Antibiotics
The medical fraternity warns that as the bacteria mutate and adapt to the medicines, millions of currently treatable infections could become life-threatening as the antibiotics in existence become redundant in the coming years.
Moreover, while resistance is a persistent issue, some 90%-95% of fatal infections involve microbes that are not drug-resistant but are difficult to treat due to patient conditions, say medical personnel.
An ever-present conflict between R&D and approval of such new drugs is how to measure the effectiveness of the antibiotics—should it be patient survival? Symptom treatment? Bacteria count or duration of treatment?
This is not to say that governments and organizations, and even the industry are not doing their bit to improve the situation. The World Health Organization and the drug industry in 2020 created a $1 billion venture capital fund to support worthy antibiotics companies.
Governments have grants and patent extension policies in place to further aid research.
But the biggest hurdle is that new drugs gain approval based on their effectiveness compared to the existing ones. Since they are roughly as effective as existing drugs, infectious disease doctors generally shun them due to the high price and scepticism.
And since there is no widespread adoption of the newer advanced antibiotic drugs, the big pharma is not interested in investing in the same. It is a complex cycle to break as profit comes before care.
