So where are antibiotics supposed to come from?
Last month I wrote about the unexpected bankruptcy of the small biotech firm Achaogen, which declared Chapter 11 despite having brought out a needed new antibiotic. Its remarkable that, in the five weeks since the company put itself up for sale, the alarm provoked by its crash hasnt died away. If anything, the concern has gotten more intense. It sounds like this: If a company that had everything going for it cant profitably produce an antibiotic, who can?
The answer may be that no one canthat the traditional structure of the pharma business, which works so well to bring forth cancer and cardiovascular and lifestyle drugs, cant profitably produce the antibiotics that society needs. Which means it may be time to stop asking pharma to make them, and create some other entitya government institute, an international nonprofit, a utilityto perform the task instead.
This sounds unthinkably radical, but a surprising number of leading thinkers about antibiotics are starting to advance the concept, out loud.
At the end of March, Lord Jim ONeillthe former chief economist of Goldman Sachs, who ran the British governments two-year Review on Antimicrobial Resistancestartled the audience at a London summit on resistance by recommending that antibiotic R&D be excised from companies and nationalized. Just take it away from them and start over, he said, excoriating pharma companies for being endless talk but no progress.
That same week, three British researchers proposed that governments band together to create an international nonprofit that would assume responsibility for discovering new compounds and conducting trials to prove their worth. One of the authors, Adam P. Robertswho is a microbiologist and antibiotic discoverer at the Liverpool School of Tropical Medicinesaid by email that if the institute found new antibiotics, they would be considered joint intellectual property, held as open science on behalf of the world and turned over to generic drug firms to be manufactured as cheaply as possible.
And two weeks ago, Rick Bright, director of Bardaa division of the US Department of Health and Human Services that functions as the governments own biotech investment firmwrote in Forbes that new antibiotics can only be achieved through novel business models and real change.
That may seem like a lot at once, but the medical communitys frustration with achieving new antibiotics has been boiling up for a while. One after another, the large pharma companies that once made antibioticsincluding AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Abbvie, Sanofi, and Novartisdeparted the specialty, claiming they couldnt make a profit on drugs that are only taken for short periods of time and that lose effectiveness to resistance every day they are on the market. That left the field to small biotechs such as Achaogen, which found the profitability crunch even harder to endure than the big companies did, because they didnt have other drug categories bringing in revenue to even out the balance sheet.
The proposals to remake antibiotic R&D into a government possession or a nonprofit concern are a response to those departures. They say, in effect: If profitability is an insoluble problem for antibiotics companies, we can solve that problem by making profit irrelevant.
Creating a whole new entity feels like it might be throwing good money after badbut Roberts says this effort could be funded by redirecting money that governments are investing and wasting. To date, he said, governments and philanthropies such as the Wellcome Trust have put more than $600 million into boosting antibiotic research, contributions that produced no results because companies shelved their proprietary findings when they abandoned their research programs or went broke.
And theres a historic precedent for government ownership of antibiotic production, dating back to the first antibiotic, penicillin. It was identified in a London laboratory in 1928, but it was only turned into a mass-produced drug in the 1940s, after the US governmentwhich needed it for the war effortgave grants to multiple companies to make it, coupled with massive military contracts to later buy it.
Organizations already exist that might serve as models for creating an international antibiotics initiative, or for doing some of the tasks an international initiative might perform. Gavi, a global vaccine alliance, guarantees that low-income countries can afford childhood vaccines by placing bulk orders on behalf of several countries at once, negotiating prices with manufacturers, and funding the purchases through a mix of government contributions and philanthropic funds. The Global Antibiotic Research and Development Partnership, meanwhile, supports research into new and abandoned antibiotics for neonatal and childhood infections and sexually transmitted diseases. Laura Piddock, its scientific director and a microbiologist at the University of Birmingham, calls the nonprofit not a replacement for pharma companies, but an alternative approach. She adds: We want to fill the gaps that no company is addressing.
But the ultimate goal of nationalized, internationally supported, nonprofit antibiotic production would be to replace pharma companiesand because they represent such an established (if malfunctioning) ecosystem, theres a lot of skepticism around the idea.
Kevin Outterson, a professor of health law at Boston University and the executive director of CARB-X, a public-private partnership that funnels money to very early stage antibiotic research, worries that consigning antibiotic R&D to nonprofits will squelch innovation. If you do that, no private investor will ever again put a nickel in a preclinical antibiotic product, he says.
What Outterson envisions instead is a for-profit public entity, possibly more than one. The closest analogue may be investor-owned public utilities, which have shareholders who receive a capped rate of returnwhich, in the case of a new antibiotic entity, would reward investment, but at a lower rate than Wall Street currently demands of pharma companies.
We have to do it in a way that actually gives some hope to the private investor, and to little startups that have 10 employees and borrowed money from their aunts and uncles to get started, who hope to get bought out at a reasonable price, he says. That's the only way we're going to have an ecosystem that works for decades.
Decades is the point. The reason the Achaogen bankruptcy is so serious isnt because of the loss of one company or drug. It is because it represents a last gaspmaybe the last gaspof a manufacturing system that has stood since the end of World War II. From this point, producing antibiotics isnt a matter of achieving one new drug, or several; the actual task is realizing a new paradigm that will guarantee production for at least as many years into the future as we have had them in the past. Whichever model governments and industry choose, it is unlikely to look like what came before.