“If you invent a mediocre antibiotic, your sales will be low; if you develop a great antibiotic, your sales will be lower.” Kevin Outterson, who runs CARB-X, told the Davos meeting of the World Economic Forum in 2020, and the line explains most of what is wrong with the business of new antibiotics.
Families take the pills in the cabinet on trust, but the pipeline behind them is thin. In April 2021 the World Health Organization published its fourth review of antibacterial drugs in clinical development. It counted 43 antibiotics and combinations. Of those, 26 act against the organisation’s priority pathogens, 12 against Mycobacterium tuberculosis and 5 against Clostridioides difficile, CIDRAP reported.
More of the same
Most of the 26 are variations on existing classes. Just seven clear any of the WHO’s tests for innovation, and only two of those work against the critical, multidrug-resistant gram-negative bacteria that leave doctors with few options. Eleven are beta-lactam combinations, a type sold for more than three decades. Nothing in the pipeline addresses extensively resistant gram-negative infections, and two named bugs, Acinetobacter baumannii and Pseudomonas aeruginosa, both carbapenem-resistant, remain badly served. There is also a shortage of oral options that would let patients with resistant infections be treated outside hospital.
Since 2017 regulators have approved 11 antibiotics; just 2 belong to a new class. WHO said 82% of recently approved antibiotics are derivatives of classes where resistance is already well established. Peter Beyer, a senior adviser in the WHO’s antimicrobial resistance division, put it plainly: “The pipeline is insufficient to counter the rising resistance in these priority bacteria.”
Why companies stay away
The reason is revenue. An antibiotic cures an infection in days or weeks, so sales volumes stay small. Doctors also hold the newest drugs in reserve to slow resistance, which squeezes sales further. Applied Clinical Trials Online noted that developing a new antimicrobial drags on for over 10 years and costs above $1.5 billion, while annual sales of about 30 percent of the new antibiotics sold between 2000 and 2015 did not exceed $100 million. Oncology drugs, by comparison, topped $500 million in 2016. Between 2016 and 2019 venture funding shrank by a factor of more than 10. Small and mid-sized biotechs make up 90 percent of the developers.
Beyer drew the same contrast with cancer, where thousands of drugs are in development. The “main reason is because the revenue you can generate with new cancer treatment is so much higher than with a new antibiotic,” he said.
Merck’s Cubicin shows how it can go wrong. Merck paid $9.5 billion for Cubist Pharmaceuticals in 2014, and Cubicin earned more than $700 million in its first nine months. Then a federal court in the U.S. struck down several patents, generics arrived, and annual sales by 2019 were barely above $360 million.
Beyer pointed to Germany and the United Kingdom, which are testing models that pay for a new antibiotic’s value to public health rather than the number of doses sold.
Sources
- WHO report highlights shortage of new antibiotics (CIDRAP)
- WHO: No antibiotic in development sufficiently addresses drug resistance (Healio)
- A Market Failure for Antimicrobial Resistant Medicines (Applied Clinical Trials Online)
