Antibiotics Currently in Clinical Development
Note: This data visualization was updated in December 2016 with new data.
As of September 2016, an estimated 40 new antibiotics1 with the potential to treat serious bacterial infections are in clinical development for the U.S. market. The success rate for clinical drug development is low; historical data show that, generally, only 1 in 5 infectious disease products that enter human testing (phase 1 clinical trials) will be approved for patients.* Below is a snapshot of the current antibiotic pipeline, based on publicly available information and informed by an external expert. It will be updated periodically, as products advance or are known to drop out of development. Because this list is updated periodically, footnote numbers may not be sequential. Please contact email@example.com with additions or updates.
- Development Phase
For definitions of drug development terms, visit: http://www.pewtrusts.org/en/research-and-analysis/analysis/2014/03/12/glossary-for-the-antibiotic-pipeline. Note: The following drugs have been removed from the pipeline. They will be included in future updates if development resumes:
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, doi:10.1038/nbt.2786. See more at http://www.pewtrusts.org/en/multimedia/data-visualizations/2014/antibiotics-currently-in-clinical-development.
- Antibiotics listed here include products containing at least one component not approved in the United States previously. All analyses were strictly limited to systemic antibiotics (drugs that work throughout the body) and drugs to treat Clostridium difficile-associated disease. The Centers for Disease Control and Prevention cited C. difficile as an urgent public health threat in a 2013 report (Antibiotic Resistance Threats in the United States, 2013, Sept. 16, 2013, http://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf). This pipeline is also limited to drugs with the potential to treat serious or life-threatening infections. Specifically excluded were drugs to treat mycobacterial infections, such as tuberculosis and Mycobacterium avium complex, H. Pylori, and biothreat pathogens. Additionally, biological products, vaccines, and locally acting drugs such as topical, ophthalmic, and inhaled products were excluded. Avibactam, a novel beta-lactamase inhibitor, is being studied in combination with three approved antibiotics, and all three were counted for this report as each combination targets a distinct set of pathogens.
- Based on the most advanced development phase for any indication according to trials registered in clinicaltrials.gov, unless direct communication from the company indicated differently. If no trials were included in clinicaltrials.gov, then the phase listed on the company website or provided directly by the company is noted. Antibiotics that have been approved will remain listed for one year following approval of the initial indication.
- A ‘yes’ in this column indicates that a drug has in vitro data showing both activity against one or more Gram-negative species that are considered ESKAPE pathogens (Enterobacter species, Klebsiella pneumoniae, Acinetobacter baumanii, or Pseudomonas aeruginosa) and the potential for clinically significant improved coverage of resistant isolates of these species relative to currently available antibiotics. Excluded are drugs that may have shown in vitro activity but currently have no relevant indications listed in this pipeline. This does not apply to phase 1 drugs whose indications are often unknown. Five drugs are listed as ‘possibly’ according to these criteria. Data from in vitro studies and mouse models suggest that TP-271 and TP-6076 could potentially meet the criteria for this column. It is suspected that OP0595 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. Similarly, there are currently no publicly available in vitro data for WCK 5222; however, information found in company press releases and trial registrations suggests that this product will meet the criteria for this column. Delafloxacin is also listed as ‘possibly.’ Although current data show the potential for improved coverage compared with currently available fluoroquinolones in acidic environments, it is not clear how this in vitro benefit will translate into clinical efficacy. This column focuses on only one area of unmet medical need. However, stakeholders often highlight resistant Gram-negative ESKAPE pathogens as an area in which innovation is urgently needed and drug discovery and development are particularly challenging. 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 Centers for Disease Control and Prevention as an urgent threat to public health. These include C. difficile, carbapenem-resistant Enterobacteriaceae, and drug-resistant N. gonorrhoeae. Excluded are drugs that may have shown in vitro activity but currently have no relevant indications listed in this pipeline. This does not apply to phase 1 drugs, where indications are often unknown. Delafloxacin, TP-271, TP-6076, and WCK 5222 are listed as ‘possibly’ in this column, for the same reasons as explicated in Note 3. Finafloxacin, OP0595, and omadacycline are also listed as ‘possibly’. These drugs have in vitro activity against Enterobacteriaceae; however, published studies have not specifically referenced whether these drugs were tested against carbapenem- resistant strains.
- Based on clinical trials currently registered in clinicaltrials.gov and/or reported qualified infectious disease product (QIDP) designations unless otherwise noted. Bolded indications are reported QIDP designations. QIDP designations are given by the Food and Drug Administration 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.
- Not currently registered on clinicaltrials.gov. Information obtained from the company via a corporate website, news release, and/or direct communication.
- Avibactam is a new beta-lactamase inhibitor being tested in conjunction with three individual antibiotics. We list two of the combinations here. Another combination, Avycaz, was approved by the FDA in February 2015.
- Nemonoxacin has been approved for community-acquired bacterial pneumonia in Taiwan; a new drug application was submitted in China.
- Taksta was granted an orphan drug designation for the indication of prosthetic joint infections.
- Registered in clinicaltrials.gov but with no current study sites within the United States.
- 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 the U.S., this drug remains listed in our pipeline.
- Phase 2 trials for finafloxacin do not currently include any U.S. study sites; however, the company indicated in a December 2012 press release that the trial was based on updated guidance from FDA.
- 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 (unpublished) have shown improved clinical outcomes in patients treated with finafloxacin compared to patients treated with the current standard of care.
- The phase 2 clinical trial for MRX-I has no specific U.S. study sites listed, but the FDA is listed as the Health Authority for this study.
- This drug has received QIDP designation, but the specific indication this designation applies to is unknown.
- 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.
- Carbavance is a combination of a cyclic boronate β-lactamase inhibitor and a previously approved carbapenem. Β-lactamase inhibitors have been paired with β-lactams in the past, but this β-lactamase inhibitor has a novel chemical structure.
- Citeline, “Pharmaprojects,” (2012), http://www.citeline.com/products/pharmaprojects.
- BioCentury, “Antibiotics NCE Pipeline,” accessed Oct. 28, 2013, http://www.biocentury.com/antibioticsncepipeline.htm.
- 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 (2013): 792–821, http://cmr.as.org/content/26/4/792.
- Centers for Disease Control and Prevention, Antibiotic Resistance Threats in the United States, 2013 (Sept. 16, 2013), http://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf.