Data Visualization

Antibiotics Currently in Clinical Development

As of September 2015, an estimated 39 new antibiotics1 with the potential to treat serious bacterial infections are in clinical development for the U.S. market and two have been approved within the last year. The success rate for clinical drug development is low; at best, only 1 in 5 candidates 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 abxpipeline@pewtrusts.org with additions or updates.

September 2015 (PDF)| March 2015 (PDF) | December 2014 (PDF) | September 2014 (PDF) | June 2014 (PDF) | February 2014 (PDF)

Drug name

Development phase2

Company

Drug class

Expected activity against resistant Gram-negative ESKAPE pathogens?3

Expected activity against a CDC urgent threat pathogen?4

Potential indication(s)?5

Drug name

Development phase2

Company

Drug class

Expected activity against resistant Gram-negative ESKAPE pathogens?3

Expected activity against a CDC urgent threat pathogen?4

Potential indication(s)?5

Ceftolozane+Tazobactam (Zerbaxa)

Approved Dec. 19,
2014

Cubist Pharmaceuticals, Inc. (wholly owned subsidiary of Merck & Co.)

Novel    cephalosporin+beta- lactamase inhibitor

Yes

No

Approved for: complicated urinary tract infections, complicated intra-abdominal infections, acute pyelonephritis (kidney infection); other potential indications: hospital-acquired bacterial pneumonia/ ventilator-associated bacterial pneumonia

Ceftazidime+Avibactam (Avycaz)

Approved Feb. 25,
201513

Allergan plc (formerly Actavis)/AstraZeneca plc

Cephalosporin + novel beta-lactamase inhibitor

Yes

Yes

Approved for: complicated urinary tract infections, complicated intra-abdominal infections, acute pyelonephritis (kidney infection); other potential indications: hospital-acquired bacterial pneumonia/ ventilator-associated bacterial pneumonia, bacteremia

WCK 4873

Phase 1

Wockhardt Ltd.

No

No

Bacterial infections17

MGB-BP-3

Phase 110

MGB Biopharma Ltd.

No

Yes

C. difficile infections

OP0595 (RG6080)

Phase 110

Meiji Seika Pharma Co., Ltd./Fedora Pharmaceuticals, Inc. (Roche licensee)

Beta-lactamase inhibitor

Possibly

Possibly

Bacterial infections

Aztreonam+Avibactam7 (ATM-AVI)

Phase 110

AstraZeneca/Allergan (formerly Actavis)

Monobactam + novel beta-lactamase inhibitor

Yes

Yes

Bacterial infections

BAL30072

Phase 1

Basilea Pharmaceutica Ltd.

Monosulfactam

Yes

Yes

Multidrug-resistant Gram-negative bacterial infections6

CRS3123

Phase 1

Crestone, Inc.

Methionyl-tRNA synthetase (MetRS) inhibitor

No

Yes

C. difficile infections

LCB01-0371

Phase 110

LegoChem Biosciences, Inc.

Oxazolidinone

No

No

Bacterial infections

TD-1607

Phase 1

Theravance Biopharma, Inc.

Glycopeptide- cephalosporin heterodimer

No

No

Acute bacterial skin and skin structure infections,6 hospital-acquired pneumonia/ ventilator-associated pneumonia,6 bacteremia6

WCK 2349

Phase 1

Wockhardt Ltd.

Fluoroquinolone (WCK 771 pro-drug)

No

No

Bacterial infections17

WCK 771

Phase 1

Wockhardt Ltd.

Fluoroquinolone

No

No

Bacterial infections17

MRX-I

Phase 216

MicuRx Pharmaceuticals, Inc.

Oxazolidinone

No

No

Acute bacterial skin and skin structure infections

Debio 1450

Phase 2

Debiopharm Group

Fabl inhibitor (Debio 1452 pro-drug)

No

No

Acute bacterial skin and skin structure infections (staphylococci-specific)

ETX0914

Phase 2

Entasis Therapeutics, Inc.

Spiropyrimidinetrione DNA gyrase inhibitor

No

Yes

Uncomplicated gonorrhea

S-649266

Phase 2

Shionogi, Inc.

Cephalosporin

Yes

Yes

Complicated urinary tract infections

POL7080

Phase 210

Polyphor Ltd.

Macrocycle (protein epitope mimetic) LptD inhibitor

Yes (Pseudomonas)

No

Ventilator-associated bacterial pneumonia (caused by Pseudomonas aeruginosa), lower respiratory tract infection, bronchiectasis

Debio 1452

Phase 2

Debiopharm Group

Fabl inhibitor

No

No

Acute bacterial skin and skin structure infections (staphylococci-specific)

Avarofloxacin

Phase 2

Allergan plc (formerly Actavis)

Fluoroquinolone

No

No

Community-acquired bacterial pneumonia, acute bacterial skin and skin structure infections

Brilacidin

Phase 2

Cellceutix Corp.

Defensin-mimetic

No

No

Acute bacterial skin and skin structure infections

Ceftaroline+Avibactam

Phase 2

AstraZeneca plc/Allergan plc (formerly Actavis)

Cephalosporin + novel beta-lactamase inhibitor

Yes

Yes

Bacterial infections6

CG400549

Phase 2

CrystalGenomics, Inc.

Fabl inhibitor

No

No

Acute bacterial skin and skin structure infections, osteomyelitis6

Finafloxacin11

Phase 212

MerLion Pharmaceuticals Pte Ltd.

Fluoroquinolone

Yes14

Possibly15

Complicated urinary tract infections, acute pyelonephritis (kidney infection), complicated intra-abdominal infections, acute bacterial skin and skin structure infections

Gepotidacin (GSK2140944)

Phase 2

GlaxoSmithKline plc

Novel bacterial topoisomerase inhibitor

No

Yes

Respiratory tract infections, acute bacterial skin and skin structure infections, uncomplicated urogenital gonorrhea

Nemonoxacin8

Phase 2

TaiGen Biotechnology Co., Ltd.

Quinolone

No

No

Community-acquired bacterial pneumonia, diabetic foot infection, acute bacterial skin and skin structure infections

Radezolid

Phase 2

Melinta Therapeutics, Inc.

Oxazolidinone

No

No

Acute bacterial skin and skin structure infections, community-acquired bacterial pneumonia

Ramoplanin

Phase 2

Nanotherapeutics, Inc.

Glycolipodepsipeptide

No

Yes

C. difficile relapse prevention6

Zabofloxacin

Phase 2

Dong Wha Pharmaceutical Co., Ltd

Fluoroquinolone

No

No

Community-acquired bacterial pneumonia

SMT 19969

Phase 2

Summit Therapeutics, Inc.

No

Yes

C. difficile-associated diarrhea

Omadacycline

Phase 3

Paratek Pharmaceuticals, Inc.

Tetracycline

Yes

Possibly15

Community-acquired bacterial pneumonia, acute bacterial skin and skin structure infections, complicated urinary tract infections

Lefamulin (BC-3781)

Phase 3

Nabriva Therapeutics AG

Pleuromutilin

No

No

Acute bacterial skin and skin structure infections, community-acquired bacterial pneumonia, hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia, osteomyelitis,6 prosthetic joint infections6

Imipenem/ cilastatin+relebactam (MK-7655)

Phase 316

Merck & Co., Inc.

Carbapenem + novel beta-lactamase inhibitor

Yes

Yes

Complicated urinary tract infections, acute pyelonephritis, complicated intra-abdominal infections, hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia

Iclaprim

Phase 318

Motif Bio plc

Dihydrofolate reductase (DHFR) inhibitor

No

No

Acute bacterial skin and skin structure infections; hospital-acquired bacterial pneumonia

Cadazolid

Phase 3

Actelion Pharmaceuticals Ltd

Quinolonyl- oxazolidinone

No

Yes

C. difficile-associated diarrhea

Taksta (Fusidic acid)9

Phase 3

Cempra, Inc.

Fusidane

No

No

Prosthetic joint infections, acute bacterial skin and skin structure infections

Carbavance (RPX7009+meropenem)

Phase 3

Rempex Pharmaceuticals, Inc. (wholly owned subsidiary of The Medicines Co.)

Meropenem + novel boronic beta-lactamase inhibitor

Yes

Yes

Complicated urinary tract infections, complicated intra-abdominal infections, hospital-acquired bacterial pneumonia/ ventilator-associated bacterial pneumonia, febrile neutropenia, bacteremia, acute pyelonephritis (some indications specifically target infections caused by carbapenem- resistant Enterobacteriaceae )

Delafloxacin

Phase 3

Melinta Therapeutics, Inc.

Fluoroquinolone

Possibly

Possibly

Acute bacterial skin and skin structure infections, hospital-acquired bacterial pneumonia,6 complicated urinary tract infections,6 complicated intra-abdominal infections6

Eravacycline

Phase 3

Tetraphase Pharmaceuticals, Inc.

Tetracycline

Yes

Yes

Complicated intra-abdominal infections, complicated urinary tract infections, hospital-acquired bacterial pneumonia6

Plazomicin

Phase 3

Achaogen, Inc.

Aminoglycoside

Yes

Yes

Complicated urinary tract infections, catheter-related bloodstream infections, hospital-acquired bacterial pneumonia/ ventilator-associated bacterial pneumonia, complicated intra-abdominal infections, acute pyelonephritis (kidney infection) (some indications specifically target infections caused by carbapenem-resistant Enterobacteriaceae)

Solithromycin

Phase 3

Cempra, Inc.

Macrolide (fluoroketolide)

No

Yes

Community-acquired bacterial pneumonia, uncomplicated urogenital gonorrhea, urethritis6

Surotomycin

Phase 3

Cubist Pharmaceuticals, Inc. (wholly owned subsidiary of Merck & Co.)

Lipopeptide

No

Yes

C. difficile-associated diarrhea

For definitions of drug development terms, visit: http://www.pewtrusts.org/en/research-and-analysis/analysis/2014/03/12/from-lab-bench-to-bedside-a-backgrounder-on-drug-development. 

Note: The following drugs have been removed from the pipeline. They will be included in future updates if development resumes:

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.

* Michael Hay et al., “Clinical Development Success Rates for Investigational Drugs,” Nature Biotechnology 32, no. 1 (2014): 40–51, doi:10.1038/nbt.2786. http://www.pewtrusts.org/en/multimedia/data-visualizations/2014/antibiotics-currently-in-clinical-development.

Endnotes

  1. 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/threat-report-2013/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.
  2. 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.
  3. 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. Two drugs are listed as ‘possibly’ according to these criteria. It is suspected that OP0595 will meet the criteria for this column, but is listed as ‘possibly’ pending public release of data and identification of the beta-lactam antibiotic with which it will be combined. 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).
  4. 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 and OP0595 are listed as ‘possibly’ in this column, for the same reasons as explicated in Note 3. Finafloxacin and omadacycline are also listed as ‘possibly’ (see Note 15).
  5. 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.
  6. Not currently registered on clinicaltrials.gov. Information obtained from the company via a corporate website, news release, and/or direct communication.
  7. Avibactam is a new beta-lactamase inhibitor being tested in conjunction with three individual antibiotics. We list all three combinations here.
  8. Nemonoxacin has been approved for community-acquired bacterial pneumonia in Taiwan; a new drug application was submitted in China.
  9. Taksta was granted an orphan drug designation for the indication of prosthetic joint infections.
  10. Registered in clinicaltrials.gov but with no current study sites within the United States.
  11. 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 in our pipeline.
  12. Phase 2 trials for finafloxacin do not currently include any U.S. study sites; however, the company indicated in a December 2012 news release that the trial was based on updated guidance from FDA.
  13. Avycaz was approved based on Phase 2 data.
  14. 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.
  15. Both finafloxacin and omadacycline have in-vitro activity against Enterobacteriacea; however, published studies have not specifically referenced whether these drugs were tested against carbapenem-resistant strains.
  16. These drugs have no specific U.S. study sites listed for one or more clinical trials, but the FDA is listed as the Health Authority for these studies.
  17. These drugs have received QIDP designations, but the specific indication this designation applies to is unknown.
  18. Iclaprim previously failed to gain approval from the FDA. Current sponsor, Motif Bio, received approval for a new clinical development program from the FDA and plans to resume development for this product. However, there was no new Phase 3 trial in clinicaltrials.gov as of September 2015.

Citations

  1. Citeline, “Pharmaprojects,” (2012), http://www.citeline.com/products/pharmaprojects.
  2. BioCentury, “Antibiotics NCE Pipeline,” accessed Oct. 28, 2013, http://www.biocentury.com/antibioticsncepipeline.htm.
  3. U.S. National Institutes of Health, “Search for Studies,” http://www.clinicaltrials.gov.
  4. 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.
  5. Michael J. Pucci and Karen Bush, “Investigational Antimicrobial Agents of 2013,” Clinical Microbiology Reviews 26 (2013): 792–821, http://cmr.asm.org/content/26/4/792.
  6. 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.

Media Contact

Linda Paris

Officer, Communications

202.540.6354