BARDA support moves antibacterial candidates from preclinical studies through advanced research and development
November 23, 2021
BARDA’s antibacterials program provides support that spans the development pipeline, ranging from preclinical and clinical research through regulatory approval and, ultimately, procurement for national preparedness. BARDA's continued efforts are critical to addressing AMR and are being highlighted to support World Antimicrobial Awareness Week (November 18-24, 2021), declared by the World Health Organization. BARDA’s core work focuses on advanced development, where we support companies through resource-intensive clinical studies to Food and Drug Administration (FDA) review, but our work starts much earlier and continues even after FDA authorization or approval.
“During Antibiotic Awareness Week, we commit to doing our part to take on the threat of antibiotic resistance and pursue strategies that will make all Americans safer and healthier,” said a proclamation by President Biden. “Every year, more than 3 million people in the United States are infected -- and nearly 50,000 are killed -- by an antibiotic-resistant germ or an infection that can occur after taking antibiotics.”
Even in the midst of the COVID-19 pandemic, antimicrobial resistance has been and continues to be one of the greatest global health threats. Efforts to combat drug resistant bacteria have reduced these infections and cut deaths by about 18% since 2013, according to the Centers for Disease Control and Prevention. But the increasing prevalence of antibiotic-resistant bacteria threatens the utility of antibiotics and opens the door to potentially untreatable infections that complicate recovery from modern medical procedures.
Establishing and maintaining an effective preparedness posture requires the development of multiple antibacterial products, which are a critical part of our layered approach to preparedness. Antibiotics are needed to treat infections caused by naturally occurring and intentionally engineered biothreats as well as secondary infections caused by antibiotic-resistant bacteria that can arise during a public health emergency or natural disaster.
Developing new products to treat resistant bacterial infections is difficult and expensive. The rarity of these drug resistant infections, combined with the desire to preserve these life-saving drugs for when they are needed most, prevents companies from recouping their investment in the research and development of antibiotics. As a result, many manufacturers have shifted their development efforts away from antibiotics.
Recognizing these challenges and the need to have effective antibiotics available for the most challenging infections, BARDA’s Antibacterials Program mitigates technical and financial barriers through public-private partnerships that provide subject matter expertise and non-dilutive funding. The goal is to provide clinicians and first responders with therapeutics that reduce illness or death caused by antibiotic-resistant infections.
Since its start in 2010, the BARDA Antibacterials program has invested over $1.6 billion in more than 120 antibacterial development products primarily via three program areas:
Of the ARD and PBS projects, 18 are currently active and 4 have been approved.
Because antimicrobial resistance remains a major global public health threat, BARDA also forms global partnerships to have an even broader reach. Together, these partnerships have led to approvals and a pipeline of candidates that target the majority of the priority pathogens identified by the U.S. Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO).
Through CARB-X, BARDA partners with international funders to support investigational new drug (IND)-enabling studies and phase 1 clinical trials. Since 2016, BARDA has provided $200 million dollars and technical support to CARB-X funded product developers of antibacterial therapeutics, preventatives, and diagnostics. Our goal is for the CARB-X program to identify and accelerate the development of early-stage candidates with potential clinical impact so that they are poised for late-stage development in the ARD portfolio. This model enables BARDA to invest strategically in areas with the greatest need.
One example of how BARDA supports development of antimicrobial product candidates is BARDA’s partnership with Vedanta Biosciences. BARDA’s non-dilutive funding and subject matter expertise helped Vedanta advance a candidate through early- to late-stage clinical development. Vedanta’s live biotherapeutic product, VE303, is in development to treat patients at high risk of recurrent Clostridioides difficile (C. difficile) infections (CDI). Patients receiving prolonged antibiotic therapy, which can occur during a public health emergency, are at increased risk for CDI. C. difficile, considered an urgent threat by the CDC, causes approximately 500,000 infections each year, including up to 165,000 recurring infections and up to 45,000 deaths in the United States. These patients suffer debilitating, often-recurrent diarrhea and colitis.
VE303 was initially funded through the CARB-X portfolio and later became the first CARB-X therapeutic to receive follow-on BARDA support for late-stage development in the ARD portfolio. The technical and financial support from CARB-X enabled Vedanta to advance VE303 rapidly through a phase 1 clinical trial, demonstrate favorable safety and pharmacokinetics/pharmacodynamics data, and select effective dosing regimens for a phase 2 clinical study. This early-stage support effectively de-risked the VE303 program, making it attractive to follow-on funding from BARDA’s antibacterials program. With ARD funding from BARDA, Vedanta completed a Phase 2 clinical trial that showed that VE303 provides a significant reduction in the odds of CDI recurrence compared to placebo and an acceptable safety profile. Based on these results, BARDA will support the pivotal phase 3 clinical trial of VE303.
The addition of VE303 to BARDA’s antibacterial portfolio aligns with BARDA’s broader interest in supporting the development of innovative, non-traditional therapies that address secondary bacterial infections and multidrug-resistant infections that complicate the response and recovery from public health emergencies.
BARDA’s work does not stop when supported products reach FDA approval. Recognizing the capital-intensive nature of post-approval requirements and clinical trials supporting the use of antibiotics in underserved patient populations like children, the antibacterials program works with companies to support these studies and improve their chance of success after approval and commercial launch. BARDA also supports the acquisition of drugs through Project BioShield contracts. The procurement of these products enables the Office of the Assistant Secretary for Preparedness and Response accomplish its life-saving mission during a public health emergency.
Recently, BARDA initiated procurement of the antibiotic NUZYRA (omadacycline) from Paratek Pharmaceuticals of Boston, Massachusetts, to treat infections caused by anthrax. Using Project BioShield authorities and funding, BARDA awarded a contract to Paratek in December 2019, potentially totaling up to $285 million over 10 years, for the late-stage development needed to achieve regulatory approval of the drug for post-exposure prophylaxis after anthrax exposure and to treat lung infections caused by inhaling anthrax spores. The contract also supports post-marketing requirements of the drug for bacterial pneumonia and enables federal procurement of NUZYRA.
BARDA’s goals include continued development of clinically impactful antibacterial drug candidates and accelerating the progression of products through clinical development to eventual consideration by the FDA for marketing authorization. We are interested in the development of a diverse array of antibacterial products, including new classes of antibiotics, non-traditional agents, and rapid diagnostics. BARDA’s innovative and effective approach to medical countermeasure development is critically needed to bring new life-saving antibacterial products to clinicians, first responders, and their patients.
If your organization has a potential innovation that can address antimicrobial resistance or other 21st century health security threats, please use this link for more information on how to arrange a meeting with BARDA.
BARDA plays a critical role in the federal government’s National Action Plan for Combatting Antibiotic-Resistant Bacteria (CARB), 2020-2025. Through the antibacterial program, BARDA has supported more than 28 public-private partnerships with industry since 2010, ranging from small biotechnology firms to global pharmaceutical companies. In addition to providing subject-matter expertise to supported companies, BARDA scientists have co-authored two papers analyzing best practices and implementation strategies for incentivizing global antibacterial drug development.
Learn more about BARDA's work in science and the impact of our countermeasures.