Combating antibiotic resistance requires new, better antibacterial drugs. BARDA is taking a unique partnership approach to engage industry in antibiotic development in an effort to combat the rise in antibiotic resistance.
BARDA established a Broad Spectrum Antimicrobials (BSA) Program in April 2010 to develop novel antibacterial and antiviral drugs to treat or prevent diseases caused by biological threats. ASPR and BARDA leadership recognized that new antibiotics are needed immediately to address the increasingly prevalent public health threat of antibiotic resistance, as well as the likelihood that antibiotic resistance will complicate the response to a public health emergency.
The BSA program provides non-dilutive funding to support product development and augments our partners existing capital raised from their investors. For laypeople, this means that BARDA provides funding companies can count on and can add to their own funding to develop a drug. If the drug is approved by the FDA, the company can sell it on the commercial market to treat antibiotic resistant infections. The approved antibiotic would then also be available during a public health emergency, if needed.
BARDA continues to establish public-private partnerships with industry to develop novel antibiotics, and we anticipate a long-term commitment to this market. Through these partnerships, we support concurrent development of candidate products for biodefense and commercial indications based on strategic and funding priorities outlined in our Broad Agency Announcement (BAA).
This strategy helps ensure that novel antibiotics progress through the development pipeline to approval for public health and commercial indications. The approach also increases the likelihood that novel antibiotics will be added to the arsenal of possible treatments available to antibiotic resistant infections. Approval of a drug for a commercial indication also helps establish a human safety database and a warm-base manufacturing capability for the drug should it be needed in a biothreat emergency.
By engaging with BARDA, our industry partners are able to receive funding and expert technical advice from BARDA for clinical studies (Phase 1-3), manufacturing, and regulatory activities. Industry partners are encouraged to visit the BARDA BAA and sign up for a TechWatch meeting with BARDA and other U.S. Government subject matter experts.
In just four years our Broad Spectrum Antimicrobials program, has funded six partnerships through the BARDA BAA and we anticipate funding additional programs using this mechanism in the future.
- In August 2010, BARDA entered into a public-private partnership with Achaogen, Inc. for the development of a drug called Plazomicin™. This novel, next-generation aminoglycoside antibiotic is being developed to treat plague and tularemia (known bioterrorism threats) as well as infections caused by carbapenem resistant Enterobacteriaceae (CRE) – which CDC Director Tom Frieden called a “nightmare bacteria”. We’re supporting a Phase 3 study of efficacy against blood stream and pneumonia caused by CRE.
- In January 2012, BARDA entered into a public-private partnership with CUBRC, Inc. in partnership with Tetraphase Pharmaceuticals, Inc. for the development of eravacycline, a novel antibiotic of the tetracycline class. BARDA funding will support studies evaluating the effectiveness [efficacy] of eravacycline against biothreat pathogens as well as Phase I clinical trials to assess eravacycline safety, clinical pharmacology studies, and drug manufacturing. The BARDA contract supports development of oral and intravenous formulations of eravacycline.
- In May 2013, BARDA entered into a public-private partnership with Cempra, Inc. for development of a novel fluoroketolide antibiotic, solithromycin for the treatment of anthrax and tularemia infections. BARDA is also supporting the development of a liquid version of the drug for children. Cempra also is developing solithromycin as a commercial indication for the treatment of community acquired bacterial pneumonia (CABP) and gonorrhea.
- In May 2013, BARDA entered into an Other Transactional Agreement with GlaxoSmithKline (GSK) to support the advanced research and development of a portfolio of novel antibiotic candidates. The Pandemic and All Hazards Preparedness Act in 2006 gave HHS the authority to enter into Other Transactional Agreements and the one with GSK was the first ever awarded by HHS. The agreement is flexible, so that antibiotic candidates can move in or out of the portfolio based on their stage and feasibility. This approach balances risk for the federal government and GSK. At the same time, the approach supports development of multiple drugs simultaneously, increasing the likelihood that one or more will succeed in achieving approval by the U.S. Food and Drug Administration.
- In June 2013, BARDA entered into a public-private partnership with Basilea Pharmaceutica Ltd for the development of BAL30072, a unique monosulfactam antibiotic that could treat a broad range of multidrug-resistant Gram-negative bacteria [including species of Pseudomonas, Acinetobacter, and Klebsiellathat are of great clinical concern]. The new antibiotic also looks promising as a treatment against biothreats like melioidosis and glanders for which there are no currently approved drugs. Under this project, Basilea will conduct clinical and non-clinical studies to evaluate the safety and efficacy of BAL30072. If approved, the new drug would provide doctors with new treatment options for severe and life threatening infections, including hospital-acquired pneumonia and complicated urinary tract infections, as well as for glanders and melioidosis.
- In February 2014, BARDA entered into a public-private partnership with Rempex Pharmaceuticals, a wholly owned subsidiary of The Medicines Company, to support the advanced research and development of a novel drug called Carbavance™, a novel carbapenem/β-lactamase inhibitor combination. During this potential five-year partnership, Rempex will develop Carbavance™ for the treatment of complicated urinary tract infections, hospital-acquired and ventilator-associated pneumonia, and infections known or suspected to be caused by carbapenem-resistant Enterobacteriaceae (CRE). BARDA will provide funding for clinical, nonclinical, manufacturing and regulatory activities to support the commercial indications of the drug. In addition, BARDA will fund the assessment of Carbavance as a treatment for melioidosis and glanders.
This post is the third part in our series Combatting Antibiotic Resistance. Next week, our blog post will focus on the specific incentives BARDA is using under the BSA program to revitalize the antibiotic pipeline and engage industryTo stay up to date as new blog posts are published, subscribe to the ASPR Blog on RSS, follow @PHEgov on Twitter or Like us on Facebook.