World AMR Congress: Fighting Anti-Microbial Resistance
The World Anti-Microbial Resistance Congress 2019 was held November 7-8 in Washington, D.C. The event drew people from 40 different countries, including government officials from the U.S. and others, multi-lateral organizations, philanthropists, physicians, academics and various industry players.
The draw, of course, is a global problem—what to do about antibiotic-resistant bacteria. According to the U.S. Centers for Disease Control and Prevention (CDC), about 2 million people each year are infected with antibiotic-resistant bacteria and 23,000 people die as a result. A recent study by the UK government estimated that by 2050, as many as 10 million people could die worldwide from antibiotic-resistant infections.
The CDC is releasing a report this month on the topic, its first report in six years. And many experts are concerned the results will show that the world is not making enough progress in this area.
Greg Frank, director of Infectious Disease Policy at the Biotechnology Innovation Organization (BIO) and executive director of Working to Fight AMR, took time to talk to BioSpace ahead of the meeting about some of the topics that will be discussed and what those concerns are. He notes that although there are larger conferences related to infectious diseases, this one is by far the largest to focus solely on drug-resistant microbial diseases. “It is a great opportunity, particularly at the end of the year, to reassess the last year on how we are doing with these issues.”
He also pointed out that he expects there to be quite a focus on how the state of the industry is deteriorating quite rapidly, and some of the relatively few biotech companies in the space are struggling to stay afloat. For example, only three of the top 50 pharmaceutical companies are working on multi-drug antibiotic resistance, largely because the market discourages antibiotic R&D. This is a significant part of the congress, which broadly addressed three areas: finding new cures; fixing a broken market; and reforming current use.
Frank says, “Almost all of the recently approved antimicrobials are last-line therapeutics, used only when absolutely necessary. Part of the reason for that is if we used them too broadly it would impact their effectiveness. They’re rarely used, which is a good thing, but unfortunately, that low frequency-of-use and the general lack of societal value placed on antibiotics has created a perfect storm where a company has a low-value product that is only used occasionally.”
The primary example of struggles in the industry is Achaogen, which in 2018 received FDA approval for Zemdri (plazomicin), an antibiotic for multi-drug-resistant (MDR) Gram-negative infections, including for complicated urinary tract infections (cUTI) and pyelonephritis. The drug launched in July 2018.
Unfortunately, at the same time, Achaogen announced plans to eliminate 80 jobs, about 28% of staff, to focus on the launch and two other research programs. In April 2019, Achaogen filed for Chapter 11 bankruptcy, and two months later auctioned off most of its assets for $16 million, royalties and assumption of certain contractual liabilities. The companies that acquired them were China companies Cipla USA and QiLu Antibiotics Pharmaceutical, and Heritage Global Partners.
The issue isn’t the science, however. It’s the market. It takes about 10 to 15 years and at least $1 billion to develop a drug. Most antibiotics, on the other hand, are inexpensive. The ones with high prices are generally reserved for rare hospital use. And in the best-case scenarios, antibiotics aren’t used at all, and in most cases are only used for a short period of time. That makes it difficult for companies to turn a profit on antibiotics, despite an increasing critical need.
Expected major topics of discussion at the congress are the role, if any, government should have in addressing these issues.
One is the DISARM Act. Government reimbursement programs and private insurers reimburse hospitals for antibiotics as a bundle rather than separately. The less a hospital pays for the components of the bundle, the more likely it is to cover its costs or be profitable.
The DISARM (Developing an Innovative Strategy for Antimicrobial Resistant Microorganisms) Act was introduced by Senators Johnny Isakson (R-GA) and Bob Casey (D-PA) in June 2019.
“Hospitals have a strong incentive to use the cheapest antibiotics possible, which aren’t all that expensive, about $14,000 per course. But they tend to lose money on the bundled payments,” Frank said.
An example is an antibiotic called Colistin or polymyxin E. It was approved for use in the U.S. in 1970, but has a lot of toxicity issues, causing it to fall out of use. However, Frank says, “in the last 10 years it has come back into use by virtue of it not having been used, so there isn’t much drug resistance to it. It is one of the last remaining options for multi-drug infections.”
But there have been newer, less-toxic antibiotics that are as good or better now on the market, but hospitals aren’t utilizing them. And this is related to the issue of bundled payments—they get reimbursed for Colistin, but not the newer, expensive drugs.
As a result, Frank believes a topic of discussion will be on whether efforts like DISARM are working or are working well enough. DISARM takes these qualifying new antibiotics out of the bundled payments, with hospitals being paid no matter which antibiotics they use, but the decision will be made based on patient needs, the stewardship programs and the supervising physician.
Frank said, “There’s a need to look at the utilization of these antibiotics right now, and where they should be if they were being utilized appropriately. There’s a realization that in order to keep these companies alive long enough, it won’t necessarily solve all these problems, which is why we need to implement other incentives to help support it.
A major question, particularly during a presidential election, is whether it will be possible to get the government and politicians to act in any meaningful way. It’s not an easy task to convince the government or the public to fund private and public companies. “I can say,” Frank said, “that presidential campaigns tend to mean not a lot of stuff gets done congressionally. We acknowledge that, for better or worse. Trying to get something done this year is our biggest objective, not only because time is of the essence, but because there’s an acknowledgment that a tough road gets harder in election years.”
Another area of interest is what the U.S. Centers for Medicare and Medicaid Services (CMS) is able to do under its own authority. “The prospective payment rules did try to address these with antimicrobials,” Frank said. “It was a good first step, but a lot more is needed because I don’t think it’s going to get us far enough down the road. But CMS is taking this issue very seriously. The coalition is trying to advance these and work with CMS to see what they can do to advance these initiatives under their own authority.”
Another component is so-called “pull” incentives, which can be a difficult political road. After the 2001 anthrax attacks in the U.S., the U.S. government made several measures to support infectious disease research and manufacturing via the Department of Defense or Health and Human Services’ Biomedical Advanced Research and Development Authority (BARDA), to secure the U.S. from chemical, biological, radiological and nuclear (CBRN) threats, as well as pandemic influenza and emerging infectious diseases. Part of this was to fund research by biopharma companies into new treatments for some of these threats and manufacture them for the Strategic National Stockpile.
Frank says these are “a far more monumental task because you’re asking the U.S. government and other governments to put forth significant amounts of money to fund companies to come to the market. This could cost $1 to $2 billion in the U.S. These are enormous sums and where do we find the money to pay for it?”
As people continue to get sick and die from drug-resistant bacterial infections, the question has to arise: will it be too little, too late?