The decline and fall of anti-bacterial drug approvals. Is there a renaissance in the making?
Yesterday the Wall Street Journal summarized the current situation in antibiotic drug development and commercialization. To summarize:
- Big Pharma is slowly returning to antibiotic (really, antibacterial) drug discovery and development
- Physicians are caught between resistance to old antibacterials and a lack of new ones
- New pricing models similar to cancer pricing are needed to make it worthwhile for Big Pharma
There is no question that the need is present, and growing rapidly. As the article points out:
There is an acute medical need for new antibiotics. Antibiotic-resistant infections now kill around 50,000 people a year in the U.S. and Europe, and that number is rising, according to the World Health Organization. In the U.S., two million people a year will contract a drug-resistant infection, with direct health-care costs of as much as $20 billion, according to the Centers for Disease Control and Prevention.
The FDA recognizes the challenge faced by both physicians and the industry, and they are responding. Last year, for example, the FDA provisionally announced a rule that states that companies who develop anti-bacterials against a select list of pathogens will be awarded with an additional five years of market exclusivity (the list is available here, while the full FDA document is available here).
Dr. Brad Spellberg, Assistant Professor of Medicine at UCLA, published an excellent summary of the problem:
In 2012, antibiotic development continues to stagnate. Two systemic antibacterial agents have been approved for use in humans by the U.S. FDA from 2008 through the current year. Compare that to sixteen that were approved from 1983-1987. In particular, we have had no new classes of antibiotics to treat Gram-negative bacilli (GNB) for more than 40 years – amazingly, the fluoroquinolones were the last new class of antibiotics to treat GNB. Meanwhile, antibiotic resistance continues to spread like wildfire, particularly among the GNB.
He also highlights the problem we as a society have with antibiotic pricing versus oncology drug pricing:
…The FDA continues to approve [antibiotics] based on disease state one at a time (pneumonia, urinary tract infection, etc.) rather than based on the organisms the antibiotic is designed to kill. Thus, companies spend $100 million for a phase III program and as a result capture as an indication only one slice of the pie. There is also imbalanced drug pricing in society. We will pay $50,000 for a course of cancer chemotherapy that prolongs life by 3 months, but we don’t want to pay more than $100 for a course of antibiotics that cures the target infection. This pricing difference is neither rational nor data-driven; there is no cost-efficacy analysis that supports cancer drug pricing. Rather, drug pricing in the U.S. is based on public perception and fear. People are terrified of cancer, but not of infections.
The notion of pricing antibiotics up to the prices for novel cancer therapies is quite disturbing, but understandable. How will Payers be convinced that a second or third line antibiotic course of therapy (let’s assume 10-14 days) can justify a $5000 price tag? Matt Herper discusses the antibiotic issue in an article at the unwieldy Forbes web site:
Governments and insurance companies need to commit to paying 10 or 50 times more than they already do if industry is going to put resources into fighting the threat of superbugs…
But when it comes to trying to produce new antibiotics, governments, insurers and hospitals seem anything but serious when they vote with their wallets. The cost of a course of branded, expensive antibiotics costs $3,000 per patient. Meanwhile, Sovaldi, a new Gilead Sciences treatment that can cure hepatitis C in combination with other drugs, costs $84,000 per treatment course. Cancer medicines that add weeks or months of life can cost $100,000 per patient. Drugs for rare diseases now commonly cost $200,000 or more per patient per year, and are seen as a quick way for biotech companies to ramp up sales.
Fortunately, it’s not only Big Pharma that’s returning to the fold. A number of start ups are getting funded on the basis of antibiotic research and drug discovery. And many of these assets are available for licensing. For example, a quick search turned up the following assets available for licensing:
- AFN-1252 is an oral and iv antibiotic with potency against all drug-resistant phenotypes of staphylococci including hospital and community-acquired MRSA.
- Nemonoxacin is a novel, non-fluorinated quinolone antibiotics with a broad spectrum of activity against various resistant pathogens, in particular hospital- or community-acquired MRSA and vancomycin-resistant bacterial strains.
- Dalbavancin is a long-acting, intravenous (IV) lipoglycopeptide for the treatment of acute bacterial skin and skin structure infections (abSSSI).
So there are encouraging signs here. We have novel antibiotics being discovered and developed in small companies, we have Big Pharma jumping into the mix, we have the FDA developing policies which encourage antibiotic drug development, and we have substantial unmet needs in major markets. Hopefully, this activity will result in a series of novel, reasonably priced antibiotic launches throughout the remainder of the decade.