Conference Presentation, Panel
Outsmarting Superbugs: What Are the Alternatives?
Milken InstituteMargaret Hamburg, Matthew Hepburn, Peter Jackson, Nancy Knight, Jeanette Mucha, Peter Piot, Peggy Hamburg, David Wallace, Lance Price
- Antimicrobial resistance (AMR) is described as an existential threat, estimated to cause 700,000 to several million deaths annually, with projections rising to 10 million deaths per year by 2050 without intervention.
- In the United States specifically, AMR causes over 23,000 deaths and 2 million infections annually.
- The economic impact of unchecked AMR is projected to mimic the 2008 financial crisis but permanently, potentially reducing global exports by 3.8% annually, increasing global healthcare costs to over $1 trillion, and causing a 5% GDP loss in low-income countries.
- AMR is exacerbated by overuse and inappropriate use of antibiotics in human healthcare, the excessive use of antibiotics in animal agriculture for growth promotion, and the dumping of pharmaceutical effluents into the environment.
- The World Health Organization (WHO) ranks antimicrobial resistance among the top 10 public health threats globally.
- The U.S. Centers for Disease Control and Prevention (CDC) has launched a yearlong "AMR Challenge" involving over 100 organizations, including private sector partners like CVS, Walmart, and Petco, to commit to stewardship and prevention.
- Carb-X has committed $80 million to support over 40 drug, diagnostic, and vaccine development projects targeting AMR.
- Peter Piot highlights that AMR is worsening the control of major infectious diseases, noting untreatable malaria in parts of Southeast Asia and the emergence of extensively drug-resistant (XDR) tuberculosis.
- Drug-resistant TB has survival rates of only 30-40% even with third-line therapies, which are highly toxic and not widely available.
- The U.K. has introduced a new five-year AMR strategy that recognizes Small and Medium Enterprises (SMEs) as the primary drivers of the drug development pipeline, with only 2 of 45 active programs coming from Big Pharma.
- The U.K. is piloting the world's first "pull incentive" for antibiotics, a trial designed to reward pharmaceutical companies based on the value of preventing AMR rather than sales volume, potentially raising drug values from pennies to tens of thousands of dollars per course.
- DARPA is investing in non-traditional approaches to AMR, including modulating the human host's immune response to infections (drawing inspiration from cancer immunotherapy) and developing DNA-based therapies to produce antibodies within the body to reduce costs.
- Cybac Inc., led by CEO Jeanette Mucha, is developing live biotherapeutics using "second-generation probiotics" to treat infections like C. diff by using beneficial bacteria to produce bacteriocins and neutralize toxins, rather than traditional broad-spectrum killing.
- Jeanette Mucha notes that venture capital often hesitates to fund microbiome startups because grants like those from CARB-X are reimbursement-based and require matching investment, creating a capital gap.
- Peter Piot emphasizes that AMR requires a societal approach, necessitating the collaboration of microbiologists, anthropologists, and political scientists to understand prescription behaviors and the lack of access to antibiotics in low-income countries.
- The Global Health Security Agenda involves over 60 countries assessing national AMR systems, where countries score an average of 2 out of 5, indicating significant gaps in laboratory systems and supply chains.
- Lance Price raises a critical concern that poor wastewater treatment in developing nations acts as a distribution system for drug-resistant bacteria, fueling a cycle of infection and antibiotic use that affects global water security.
- Peggy Hamburg notes the FDA has made progress in limiting antibiotic use in animal agriculture for growth promotion but acknowledges that clinical trial structures for new antibiotics remain too rigid and require further flexibility.
- Peter Jackson warns against "sealed patents" or restricting international collaboration, arguing that new drugs must be available where resistant strains are endemic, and that intellectual property must be robust enough to allow investors to profit as developing markets grow.
- A recent example cited involves a company that successfully developed and approved a new antibiotic through CARB-X but subsequently went out of business due to an inability to effectively sell the product due to cost and provider education barriers.