Antibiotic innovation is ailing. ‘Brain drain’ may kill it

In today’s labor market, good help is hard to find. For companies developing antibiotics, it’s becoming nearly impossible.

Three years ago, I became CEO of the AMR Action Fund, which is investing approximately $1 billion in biotech companies developing treatments for antimicrobial-resistant infections, a growing global health crisis that now contributes to 4.9 million deaths every year. I have spent most of my career developing antibiotics and investing in biotechnology companies, so I was aware of the scientific and financial headwinds we’d be up against — including workforce challenges. The latter is worse than I expected, and I now worry the field is suffering irreparable harm from a prolonged period of “brain drain” that could affect everything from how new antibiotics are discovered to regulators’ ability to evaluate antibiotic candidates in the future.

Antibiotics are arguably the most important drug class ever discovered. They have dramatically extended the average human lifespan, saved many millions of lives, and transformed modern medicine. The quest for these miracle cures also inspired generations of microbiologists and chemists who devoted their careers to discovering and developing new antibiotics.

That’s no longer the case. In today’s life sciences market, antibiotics represent a perilous career path with diminishing opportunities, and researchers young and old are steering clear. A recent analysis from The AMR Industry Alliance estimated that there are only 3,000 active researchers in the world focused on antibiotic resistance, compared with some 46,000 cancer researchers. The report also found that the number of individuals listed as authors on publications related to antibiotic resistance declined by 50% from a high of 3,599 in 1995 to just 1,827 in 2020.

To understand this loss of talent and drop in output, it helps to understand the unfavorable economics of antibiotic research and development. It can cost a billion dollars or more and take a decade to develop a new antibiotic and get it approved. But new ones should be prescribed sparingly to conserve their effectiveness for as long as possible because bacteria quickly evolve resistance to them. In short, we don’t want to abuse new antibiotics as we have previously; we want to save them for worst-case scenarios. But that’s a losing proposition in today’s market, where a drug’s value is pinned to the volume of sales.

Unable to generate reasonable returns, most large pharmaceutical companies have stopped antibiotic R&D. At the same time, private investors have largely abandoned smaller biotech companies in this space: Venture capital funding for U.S.-based antibacterial-focused companies totaled $1.6 billion between 2011 and 2020 compared with $26.5 billion for oncology companies. This one-two punch has dealt a blow to scientists on all rungs of the antibiotic career ladder.

I recently talked with a colleague who worked for a large pharmaceutical company that closed its antibiotics program several years ago. He estimated the company laid off 40 researchers at the time. Of those, only five stayed in the field of antibiotics, himself included.

An identical situation played out at Achaogen, the Bay Area biotech that developed and earned FDA Breakthrough Therapy Designation and approval for plazomicin, an antibiotic effective against tough-to-treat gram-negative bacteria. Yet Achaogen was unable to weather the punishing market forces. Eight months after its achievement, the company declared bankruptcy in April 2019.

One of Achaogen’s co-founders, Ryan Cirz, estimated that of the approximately 60 antibiotic specialists at the company, only he and five others are still working in the field. “It’s a special phenotype that’s sticking it out right now,” he half joked, adding that when Achaogen closed, he encouraged colleagues to go into fields other than antibiotics “because I wanted the young scientists on my team to have a more stable environment in which to grow their careers.”

The older generations of scientists who have brought antibiotics through clinical trials and to patients are retired, or soon will be, and young scientists aren’t being trained in antibiotic research in meaningful numbers. This double-siphoned brain drain is already hampering R&D: In 2022, 20 times more patents were awarded for cancer-related innovations than antibiotic-related innovations, according to the AMR Industry Alliance report.

The U.S. and the world cannot afford to fall any further behind on securing effective and safe treatments for antibiotic-resistant infections. They now kill more people than malaria or HIV/AIDS, and the financial costs are staggering. The CDC estimates that drug-resistant infections add $4.6 billion to the nation’s health care bill each year. Globally, the cost of antimicrobial resistance could hit $1 trillion annually by 2050. Yet there are only 27 drug candidates in clinical development targeting the bacteria that the World Health Organization has declared a priority, and most of those compounds will fail in clinical testing. By comparison, some 1,600 cancer treatments and cancer vaccines are currently in clinical development.

To fight an existential-scale threat like antibiotic resistance, the world needs all the brainpower it can muster. Training grants and funding from the National Institutes of Health and similar efforts supported by universities and philanthropies are incredibly important. But they’re not enough to turn around decades of decline, and those institutions cannot take drugs through the clinic and to the people who need them. To drive long-term innovation and access, investors and industry need to come back to this fundamental field of medicine. That won’t happen, however, until policymakers address the market failures that have hobbled antibiotic development.

Scientists who go into drug development want to innovate therapies that save lives and contribute to a healthier society. Antibiotics offer enormous opportunity in that regard and are foundational to health care. But until there’s a vibrant ecosystem with viable career paths forward and upward, it’s hard to blame them for applying their talents elsewhere when society and policymakers continue to take antibiotics for granted.

Henry Skinner is the CEO of the AMR Action Fund.

date 03/06/2024
source STAT News
Author Henry Skinner