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solithromycin approval, solithromycin
Solithromycin trade name Solithera is a ketolide antibiotic undergoing clinical development for the treatment of community-acquired pneumonia and other infections

Solithromycin exhibits excellent in vitro activity against a broad spectrum of Gram-positive respiratory tract pathogens, including macrolide-resistant strains Solithromycin has activity against most common respiratory Gram-positive and fastidious Gram-negative pathogens, and is being evaluated for its utility in treating gonorrhea


  • 1 Pre-clinical studies
  • 2 Clinical trials
  • 3 Structure
  • 4 Mechanism of action
  • 5 Side effects
  • 6 Development
  • 7 Commercial aspects
  • 8 Intellectual property
  • 9 References
  • 10 Further reading

Pre-clinical studies

An in vivo pre-clinical study performed by Jeffrey Keelan done in sheep may provide a prophylactic approach for intrauterine infections during pregnancy This study was carried out by administering solithromycin to pregnant sheep, resulting in effective concentrations greater than 30 ng/ml in the fetal plasma, maternal plasma and amniotic fluid A single maternal dose maintained these concentrations for over 12 hours

Clinical trials

  • May 2011: solithromycin is in a Phase 2 clinical trial for serious community-acquired bacterial pneumonia and in a Phase 1 clinical trial with an intravenous formulation
  • September 2011: solithromycin demonstrated comparable efficacy to levofloxacin with reduced adverse events in Phase 2 trial in people with community-acquired pneumonia
  • January 2015: in a Phase 3 clinical trial for community-acquired bacterial pneumonia, Solithromycin administered orally demonstrated statistical non-inferiority to the fluoroquinolone, Moxifloxacin
  • July 2015: patient enrollment for the second Phase 3 clinical trial Solitaire IV for community-acquired bacterial pneumonia was completed with results expected in Q4 2015
  • Oct 2015: IV to oral solithromycin demonstrated statistical non-inferiority to IV to oral moxifloxacin in adults with community-acquired bacterial pneumonia
  • July 2016: Cempra announces FDA acceptance of IV and oral formulations of Solithera solithromycin New drug applications for the treatment of community-acquired bacterial pneumonia


X-ray crystallography studies have shown solithromycin, the first fluoroketolide in clinical development, has a third region of interactions with the bacterial ribosome, as compared with two binding sites for other ketolides

The only previously marketed ketolide, telithromycin, suffers from rare but serious side effects Recent studies have shown this to be likely due to the presence of the pyridine-imidazole group of the telithromycin side chain acting as an antagonist towards various nicotinic acetylcholine receptors Solithromycin differs from telithromycin because the side chain does not significantly antagonize nicotinic acetylcholine receptors Instead of the pyridine-imidazole group used on telthromycin, this molecule has a triazole-phenylamine moiety

Mechanism of action

Solithromycin inhibits bacterial translation by binding to the 23S ribosomal RNA to inhibit translation Preventing the offending bacteria from synthesizing proteins

Side effects

During a clinical study, some patients presented with elevated liver enzymes, which can be indicative of hepatotoxicity This prompted the FDA Antimicrobial Drugs Advisory Committee to vote that the risk to the liver has not been adequately characterized and that further studies need to be conducted To this extent, the FDA requires a 9,000 patient safety trial as well as restricting the drug for patients with limited options


In April 4, 2008 the investigational new drug application for solithromycin capsules was submitted under NDA number 209006, with the intravenous formulation submitted under the number 209007 From studies of pharmacokinetics, safety and efficacy several issues were found There is variable absorption which can result in subtherapeutic drug concentrations and even therapy failure Additionally, there are significant drug-drug interactions affecting solithromycin concentrations as well the concentrations of the offending drugs There is also a narrow therapeutic margin which can make this drug challenging to dose

Solithromycin is cGMP compliant with FDA protocol

Commercial aspects

Cempra's general plan is to develop solithromycin develop products through late stage clinical trials and sell them to their hospital based sales force or through partnerships, which would need negotiations with larger pharmaceutical companies There are several manufacturing plants used such as Wockhardt Limited and Hospira Incorporated manufacturing facilities as well as Uquifa Laboratories, an alternative GMP facility

Intellectual property

Due to the fact that bringing new products to the market takes a significant investment of time and money, companies place considerable importance on patent protection for new products Solithromycin is a new chemical entity from the macrolide library of compounds that were licensed by Optimer It is covered by a series of patents and patent applications which claim the composition of matter of solithromycin There are also patents surrounding the synthesis and purification of this substance For example, patent EP3190122 A1 presents a novel, efficient route of synthesis that bypasses the need for chromatographic purification which saves time


  1. ^ Reinert RR June 2004 "Clinical efficacy of ketolides in the treatment of respiratory tract infections" The Journal of Antimicrobial Chemotherapy 53 6: 918–27 doi:101093/jac/dkh169 PMID 15117934 
  2. ^ http://wwwcempracom/research/antibacterials/
  3. ^ Woolsey LN; Castaneira M; Jones RN May 2010 "CEM-101 activity against Gram-positive organisms" Antimicrobial Agents and Chemotherapy 54 5: 2182–2187 doi:101128/AAC01662-09 PMC 2863667  PMID 20176910 
  4. ^ Farrell DJ; Sader HS; Castanheira M; Biedenbach DJ; Rhomberg PR; Jones RN June 2010 "Antimicrobial characterization of CEM-101 activity against respiratory tract pathogens including multidrug-resistant pneumococcal serogroup 19A isolates" International Journal of Antimicrobial Agents 35 6: 537–543 doi:101016/jijantimicag201001026 PMID 20211548 
  5. ^ McGhee P; Clark C; Kosowska-Shick K; Nagai K; Dewasse B; Beachel L; Appelbaum PC January 2010 "In Vitro Activity of Solithromycin against Streptococcus pneumoniae and Streptococcus pyogenes with Defined Macrolide Resistance Mechanisms" Antimicrobial Agents and Chemotherapy 54 1: 230–238 doi:101128/AAC01123-09 PMC 2798494  PMID 19884376 
  6. ^ Putnam, Shannon D; Castanheira, Mariana; Moet, Gary J; Farrell, David J; Jones, Ronald N 2010 "CEM-101, a novel fluoroketolide: antimicrobial activity against a diverse collection of Gram-positive and Gram-negative bacteria" Diagnostic Microbiology and Infectious Disease 66 4: 393–401 doi:101016/jdiagmicrobio200910013 PMID 20022192 
  7. ^ Putnam, Shannon D; Sader, Helio S; Farrell, David J; Biedenbach, Douglas J; Castanheira, Mariana 2011 "Antimicrobial characterisation of solithromycin CEM-101, a novel fluoroketolide: activity against staphylococci and enterococci" International Journal of Antimicrobial Agents 37 1: 39–45 doi:101016/jijantimicag201008021 PMID 21075602 
  8. ^ Keelan, J A; Kemp, M W; Payne, M S; Johnson, D; Stock, S J; Saito, M; Fernandes, P; Newnham, J P 4 November 2013 "Maternal Administration of Solithromycin, a New, Potent, Broad-Spectrum Fluoroketolide Antibiotic, Achieves Fetal and Intra-Amniotic Antimicrobial Protection in a Pregnant Sheep Model" Antimicrobial Agents and Chemotherapy 58 1: 447–454 doi:101128/AAC01743-13 
  9. ^ "Intravenous IV Administration of Cempra Pharmaceutical's Solithromycin CEM-101 Demonstrates Excellent Systemic Tolerability in a Phase 1 Clinical Trial" 7 May 2011 
  10. ^ "Cempra antibiotic compound as effective, safer than levofloxacin" 15 Sep 2011 
  11. ^ http://investorcempracom/releasedetailcfmReleaseID=889300 4 Jan 2015
  12. ^ http://investorcempracom/releasedetailcfmReleaseID=920866 7 July 2015
  13. ^ http://investorcempracom/releasedetailcfmReleaseID=936994
  14. ^ http://investorcempracom/releasedetailcfmReleaseID=978096
  15. ^ Llano-Sotelo B, Dunkle J, Klepacki D, Zhang W, Fernandes P, Cate JH, Mankin AS 2010 "Binding and Action of CEM-101, a New Fluoroketolide Antibiotic That Inhibits Protein Synthesis" Antimicrobial Agents and Chemotherapy 54 12: 4961–4970 doi:101128/AAC00860-10 PMC 2981243  PMID 20855725 
  16. ^ Bertrand D, Bertrand S, Neveu E, Fernandes P 2010 "Molecular characterization of off-target activities of telithromycin: a potential role for nicotinic acetylcholine receptors" Antimicrobial Agents and Chemotherapy 54 12: 599–5402 doi:101128/AAC00840-10 PMC 2981250  PMID 20855733 
  17. ^ Fernandes, Prabhavathi; Martens, Evan; Bertrand, Daniel; Pereira, David December 2016 "The solithromycin journey—It is all in the chemistry" Bioorganic & Medicinal Chemistry 24 24: 6420–6428 doi:101016/jbmc201608035 
  18. ^ Owens, Brian 7 March 2017 "Solithromycin rejection chills antibiotic sector" Nature Biotechnology 35 3: 187–188 doi:101038/nbt0317-187 
  19. ^ Owens, Brian 7 March 2017 "Solithromycin rejection chills antibiotic sector" Nature Biotechnology 35 3: 187–188 doi:101038/nbt0317-187 
  20. ^ "FDA Briefing Document Solithromycin Oral Capsule and Injection Meeting of the Antimicrobial Drugs Advisory Committee AMDAC" PDF wwwfdagov Retrieved 31 October 2017 
  21. ^ "Cempra, Inc - Annual Report" investorcempracom 
  22. ^ "Cempra Annual Report" investorcempracom 
  23. ^ "Cempra Receives Complete Response Letter From FDA For Solithromycin NDAs NASDAQ:CEMP" investorcempracom 
  24. ^ "Cempra, Inc - Annual Report" investorcempracom 
  25. ^ "A novel synthetic pathway towards solithromycin and purification thereof" 2017 

Further reading

  • Profile of and Research on Solithromycin

solithromycin, solithromycin approval, solithromycin clinical trials, solithromycin gonorrhea, solithromycin manufacturer, solithromycin moxifloxacin, solithromycin nda, solithromycin phase 3 data, solithromycin safety, solithromycin structure

Solithromycin Information about


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    Solithromycin beatiful post thanks!


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