For definitions of drug development terms, visit: https://www.pewtrusts.org/en/research-and-analysis/articles/2014/03/12/glossary-for-the-antibiotic-pipeline.
Note: The following drugs have been removed from the pipeline. Removed candidates will be included in future updates if development resumes. In the case of the September 2017 update, candidates were added to reflect the expanded global scope of the pipeline.
December 2018 review: No changes.
June 2018 review: Cadazolid, DS-2969, GSK3342830, and Zabofloxacin were removed during the June 2018 review. These drugs were either no longer included in the research and development pipelines on the company website, or there was direct communication from the company regarding the status of the drugs.
September 2017 review: The antibiotics pipeline was expanded to include global development. With the expanded global methodology, the following antibiotics were added: lascufloxacin, AIC499, and AAI-101. Ramoplanin and TD-1607 were removed during the September 2017 review because they were no longer included in the research and development pipelines on the company’s website. Aztreonam + Avibactam was removed from the pipeline because avibactam is an approved beta-lactamase inhibitor.
March 2017 review: Ceftaroline + Avibactam was removed during the March 2017 review because it was no longer included in the research and development pipelines on the company’s website.
September 2016 review: BAL30072 was removed during the September 2016 review because it was no longer included in the research and development pipelines on the company website.
March 2016 review: Radezolid, Debio 1452, avarofloxacin, and surotomycin were removed during the March 2016 review. Radezolid was removed because systemic indications for this product were no longer included in the development plans listed on the sponsor website. Debio 1452, avarofloxacin, and
surotomycin were no longer included in the research and development pipelines on the company website.
September 2015 review: No changes.
March 2015 review: No changes.
December 2014 review: EDP-788 (Enanta Pharmaceuticals) and TD-1792 (Theravance Biopharma) were removed during the December 2014 review. These drugs were either no longer included in the research and development pipelines on the company website, or there was direct communication from the company regarding the status of the drugs. Additionally, GSK-2696266, which had been removed during the September 2014 review, is included in this pipeline again as S-649266, which is being developed by Shionogi.
September 2014 review: GSK-2696266 and GSK-1322322 (GlaxoSmithKline), ACHN-975 (Achaogen), and LFF571 (Novartis) were removed during the September 2014 review. These drugs were either no longer included in the research and development pipelines on the company website, or there was direct communication from the company regarding the status of the drugs.
June 2014 review: Ceftobiprole, an antibiotic developed by Basilea Pharmaceutica, had been included in our analysis; however, the company announced in June 2014 that it is not pursuing further development in the United States until a partner has been acquired. As of April 2016, Basilea announced a partnership with BARDA for Phase 3 development of ceftobiprole in the United States. This product will be included in our pipeline once development commences.
* Michael Hay et al., “Clinical Development Success Rates for Investigational Drugs,” Nature Biotechnology 32, no. 1 (2014): 40–51, https://www.ncbi.nlm.nih.gov/pubmed/24406927.
- Drugs with the potential to treat C. difficile-associated disease are also included in this resource, even though they do not necessarily work systemically, as the Centers for Disease Control and Prevention (CDC) cited C. difficile as an urgent public health threat in a 2013 report (“Antibiotic Resistance Threats in the United States, 2013”: http://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf). Specifically excluded are drugs to treat mycobacterial infections, such as tuberculosis and Mycobacterium avium complex, Helicobacter pylori, and biothreat pathogens. Locally acting drugs such as topical, ophthalmic, and inhaled products are also excluded. Biological products, including vaccines and antibodies, are tracked separately in Pew’s nontraditional pipeline (“Nontraditional Products for Bacterial Infections in Clinical Development,” http://www.pewtrusts.org/en/research-and-analysis/data-visualizations/2017/nontraditional-products-for-bacterial-infections-in-clinical-development).
- Based on the most advanced development phase for any indication according to trials registered in a government clinical trial registry (United States, http://www.clinicaltrials.gov, Australian New Zealand Clinical Trials Registry, http://www.anzctr.org.au, European Union Clinical Trials Register, https:// www.clinicaltrialsregister.eu, Japan Pharmaceutical Information Center, http://www.clinicaltrials.jp), unless direct communication from the company indicated differently. If no trials were included in a clinical trial registry, then the phase listed on the company website or provided directly by the company is noted by footnote 6. Antibiotics that have been approved will remain listed for one year following approval of the initial indication. The country and regulatory agency that approved the drug will be indicated in parentheses. Antibiotics that are approved in a country outside of the U.S., but are still in clinical development for the U.S. market, will remain in the pipeline and noted.
- A “yes” in this column indicates that a drug has in vitro data showing both activity against one or more Gram-negative bacteria that are considered ESKAPE pathogens (Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, or Enterobacter species) and the potential for clinically significant improved coverage of resistant isolates of these species relative to currently available antibiotics. Excluded drugs may have shown in vitro activity against an ESKAPE pathogen(s), but currently have no listed potential indications that are caused by these pathogens. This exclusion generally does not apply to Phase 1 drugs whose indications have not yet been identified. Four drugs are listed as “possibly” according to these criteria. It is suspected that SPR741 will meet the criteria for this column, but is listed as “possibly” pending identification of the beta-lactam antibiotic with which it will be combined. This column is based on information available in the literature, but we welcome any additional information a company may be able to provide. The column definition was revised in March 2015. In previous versions of this chart, the column included all drugs with Gram-negative activity (including drugs active against Neisseria gonorrhoeae or Haemophilus influenzae).
- A “yes” in this column indicates a drug with the potential to address one of the pathogens identified by the CDC as an urgent threat or World Health Organization (WHO) critical threat. The target pathogen is listed in parentheses. CDC urgent threats include C. difficile, carbapenem-resistant Enterobacteriaceae (CRE), and drug-resistant N. gonorrhoeae. WHO antibiotic-resistant critical priority pathogens include carbapenem-resistant A. baumannii (CRAB), carbapenem-resistant P. aeruginosa (CRPA), and carbapenem-resistant/extended spectrum β-lactamase producing Enterobacteriaceae (WHO, “Global Priority List of Antibiotic-Resistant Bacteria to Guide Research, Discovery, and Development of New Antibiotics” (2017), http://www.who.int/medicines/publications/global-priority-list-antibiotic-resistant-bacteria/en). A “possibly” in this column indicates a drug with activity information reported by the company via a corporate website, news release, or direct communication, and/or with inconclusive in vitro data. However, SPR741 is listed as “possibly” for the same reason as explained in Endnote 3. This column was revised in September 2017 to include WHO’s critical threat pathogens.
- Based on clinical trials currently registered on a government clinical trial registry, and/or reported qualified infectious disease product (QIDP) designations, unless otherwise noted. Bolded indications are reported QIDP designations. QIDP designations are given by the FDA to antibiotics intended to treat serious or life-threatening infections. QIDPs are eligible to receive benefits under the Generating Antibiotic Incentives Now Act (signed into law as part of the Food and Drug Administration Safety and Innovation Act), including expedited FDA review and extended exclusivity for approved products.
- Information not currently registered on a clinical trial registry. Information obtained from the company via a corporate website, news release, and/or direct communication.
- This antibiotic has been approved in a country outside the U.S., but remains in the pipeline because it is currently in development for the U.S. market. Nemonoxacin has been approved for community-acquired bacterial pneumonia in Taiwan, Province of China and China. Taksta (fusidic acid) has been approved for acute bacterial skin and soft tissue infections in outside markets. Ceftobiprole has been approved for community-acquired pneumonia and hospital-acquired bacterial pneumonia in outside markets. SPR994 has been approved for pneumonia, otitis media, and sinusitis in Japan.
- This drug has been granted an orphan designation from the FDA. Taksta received designation for the indication of prosthetic joint infections and Iclaprim for cystic fibrosis lung infections.
- Products added after expanded methodology in September 2017 pipeline update to include global antibiotic development (see methodology section for further details on determining product inclusion). Currently, there is no public information available indicating that these antibiotics are in development for the U.S. market.
- In February 2015, FDA approved an otic suspension formulation of finafloxacin to treat acute otitis externa. Because a systemic formulation of finafloxacin has not received approval in any country, this drug remains listed in our pipeline. Finafloxacin has shown the potential for improved activity under certain conditions, namely, acidic environments. Additionally, a company press release noted that Phase 2 complicated urinary tract infection study results have shown improved clinical outcomes in patients treated with finafloxacin compared to patients treated with the current standard of care.
- A novel drug class is defined as a core chemical structure (scaffold) that has not previously been used systemically as an antibacterial in humans.
- A target is defined as novel if the drug acts on a bacterial structure that has not previously been targeted by a systemic antibacterial in humans.
- SPR741 is an antibiotic potentiator that makes the outer membrane of Gram-negative bacteria more permeable, increasing the entry and, therefore, the efficacy of antibiotics. The antibiotic that SPR741 will be paired with has not yet been announced.
- Delpazolid (LCB01-0371) is also in development for tuberculosis, but remains in the pipeline because it is also being developed for bacterial infections.
- This is the prodrug form of the antibiotic, which has the same mechanism of action and core chemical structure, and is being developed for the distinct benefit of being able to be administered in other ways, e.g., oral or intravenously.
- ETX2514SUL is also in development as a combination with imipenem and cilastatin. With this combination, in vitro activity against CRE and possibly CRPA has been shown.
- Citeline, “Pharmaprojects,” (2012), http://www.citeline.com/products/pharmaprojects.
- U.S. National Institutes of Health, “Search for Studies,” http://www.clinicaltrials.gov.
- Helen W. Boucher et al., “10 x ’20 Progress—Development of New Drugs Active Against Gram-Negative Bacilli: An Update From the Infectious Diseases Society of America,” Clinical Infectious Diseases 56 (2013): 1685-94, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3707426.
- Michael J. Pucci and Karen Bush, “Investigational Antimicrobial Agents of 2013,” Clinical Microbiology Reviews 26, no. 4 (2013): 792-821, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3811234.
- Centers for Disease Control and Prevention, “Antibiotic Resistance Threats in the United States, 2013” (2013), http://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf.
- World Health Organization, “Global Priority List of Antibiotic-Resistant Bacteria to Guide Research, Discovery, and Development of New Antibiotics” (2017), http://www.who.int/medicines/publications/global-priority-list-antibiotic-resistant-bacteria/en.
- World Health Organization, “Antibacterial Agents in Clinical Development: An Analysis of the Antibacterial Clinical Development Pipeline, Including Tuberculosis,” (2017), http://www.who.int/medicines/areas/rational_use/antibacterial_agents_clinical_development/en/.