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This is an old revision of this page, as edited by Kdrichards (talk | contribs) at 21:44, 17 November 2009 (→Fidaxomicin – existing text including suggested changes). The present address (URL) is a permanent link to this revision, which may differ significantly from the current revision.

Clostridium difficile page – suggested updates


Treatments in development include:

  • Fidaxomicin, previously known as OPT-80 or PAR-101, is the first of a new class of antibiotics, the macrocyclics. In clinical studies, fidaxomicin has demonstrated that it is narrow spectrum and minimally absorbed after oral administration.[1] It is currently being evaluated in double-blind, randomized, multicenter international Phase III clinical trials vs. oral vancomycin. Results from the first phase III North American trial were presented publicly in November 2008. Fidaxomicin has received fast track designation from the FDA and is being developed by Optimer Pharmaceuticals, Inc.
  • CDA-1 and CDB-1 (also known as MDX-066/MDX-1388 and MBL-CDA1/MBL-CDB1) is an investigational, monoclonal antibody combination co-developed by Medarex and Massachusetts Biologic Laboratories (MBL) to target and neutralize C. difficile toxins A and B, for the treatment of CDI. Merck & Co., Inc. gained worldwide rights to develop and commercialize CDA-1 and CDB-1 through an exclusive license agreement signed in April 2009. It is intended as an add-on therapy to one of the existing antibiotics to treat CDI.
  • Nitazoxanide is a synthetic nitrothiazolyl-salicylamide derivative indicated as an antiprotozoal agent (FDA-approved for the treatment of infectious diarrhea caused by Cryptosporidium parvum and Giardia lamblia) and is also currently being studied in C. difficile infections vs. Vancomycin by Romark Laboratories, L.C.
  • Rifaximin is a clinical-stage semi synthetic, rifamycin-based non-systemic antibiotic for CDI. It is FDA-approved for the treatment of infectious diarrhea and being developed by Salix Pharmaceuticals.


Prulifloxacin page – existing text including suggested changes

Prulifloxacin (INN, codenamed NM441 and AF 3012; trade names Chinoplus, Keraflox, Quisnon, Unidrox and Sword) is a broad-spectrum fluoroquinolone antibiotic. It is a prodrug, and is metabolized in the body to the active compound ulifloxacin (also known as AF 3013), which has potent activity against gram-negative bacilli, including the bacterial pathogens associated with traveler’s diarrhea.[2][3] It was developed by Nippon Shinyaku Co. and in-licensed by Optimer Pharmaceuticals in 2004 for development and commercialization in the U.S. Prulifloxacin has a long half-life and may therefore be taken only once a day.

In clinical trials, prulifloxacin appeared as effective as ciprofloxacin, co-amoxiclav or pefloxacin in the treatment of bronchitis exacerbations or lower urinary tract infections. It was tolerated as well as ciprofloxacin.

Prulifloxacin has been approved for the treatment of uncomplicated and complicated urinary tract infections, community-acquired respiratory tract infections in several European countries, and gastroenteritis including infectious diarrheas in Japan.[4]

In the United States, India, Guatamala, Mexico and Peru, prulifloxacin has completed two phase III clinical trials for the treatment of traveler's diarrhea. Data from the two trials and 550 patients with infectious diarrhea demonstrated that prulifloxacin provides resolution of diarrhea in 24-32 hours, representing a statistically significant reduction in the duration of diarrhea compared to placebo (p<0.0001). The majority of patients receiving placebo in the two studies failed to achieve wellness by their test-of-cure visit. The overall safety profiles are similar for prulifloxacin as compared to placebo. Across both Phase III trials, 5 out of 550 subjects discontinued due to adverse events (3 prulifloxacin and 2 placebo).[5][5]

Fidaxomicin – existing text including suggested changes

Fidaxomicin (also known as lipiarmycin, lipiarmycin A3, tiacumicin B, clostomicin B1, and OPT-80) is a new narrow spectrum macrocyclic antibiotic drug. It is non-systemic, meaning it is minimally absorbed into the bloodstream, it is bactericidal, and it has demonstrated selective eradication of pathogenic Clostridium difficile with minimal disruption to the multiple species of bacteria that make up the normal, healthy intestinal flora. The maintenance of normal physiological conditions in the colon can reduce the probability of clostridium difficile infection recurrence.[6][7]

It is being developed by Optimer Pharmaceuticals for treatment of Clostridium difficile infection. It is administered orally.

It works by inhibiting the bacterial enzyme RNA polymerase. It is active against gram positive bacteria especially clostridia.

Clinical trials

Good results were reported in 2009 from a phase III trial comparing the efficacy and safety of fidaxomicin with vancomycin for the treatment of Clostridium difficile Infection, or CDI. The study met its primary endpoint of clinical cure, showing that fidaxomicin was non inferior to oral vancomycin (92.1% vs. 89.8%). In addition, the study met its secondary endpoint of recurrence: 13.3% of the subjects had a recurrence with fidaxomicin vs. 24.0% with oral vancomycin, p=0.004. The study also met its exploratory endpoint of global cure (77.7% for fidaxomicin vs. 67.1% for vancomycin p=0.006.[8] Clinical cure was defined as patients requiring no further CDI therapy two days after completion of study medication, as determined by the investigator. Subjects were followed up for four weeks after the end of therapy for recurrence of the disease, defined as return of diarrhea and confirmed by a positive toxin test. Global cure was defined as patients who were cured at the end of therapy and did not have a recurrence. The incidence of treatment-emergent adverse events such as nausea, hypokalemia and headache, and serious adverse events such as pneumonia, congestive cardiac failure and anemia between the fidaxomicin and oral vancomycin arms was similar and the safety profile of the two drugs was similar. Deaths were similar in both groups (5.3% for fidaxomicin vs. 6.5% for vancomicin), and no death was considered related to the study drug, as determined by the investigators.[9]

A second Phase 3 clinical trial of the same design is currently ongoing in North America and Europe.[10] Fidaxomicin has been granted fast track status by the FDA.

Optimer Pharmaceuticals

Optimer Pharmaceuticals, Inc. is a biopharmaceutical company focused on discovering, developing, and commercializing anti-infective products to treat serious infectious diseases such as ''Clostridium difficile'' infection (CDI) and travelers’ diarrhea.

Optimer has two anti-infective product candidates under development. Fidaxomicin, formerly known as OPT-80, is currently in Phase 3 worldwide clinical development for CDI. Prulifloxacin is an antibiotic which has completed two Phase 3 clinical trials for the treatment of travelers’ diarrhea, a form of infectious diarrhea.

History

Optimer Pharmaceuticals was founded in 1998 by Michael Chang (President and CEO), Chi-Huey Wong (Professor, The Scripps Research Institute and President, Academia Sinica, Taiwan) and Samuel Danishefsky (Professor, Memorial Sloan-Kettering Cancer Center and Columbia University). Michael Chang remains president and CEO. The Company headquarters and R&D laboratory are located in San Diego, California and has one subsidiary, Optimer Biotechnology, Inc. (OBI) located in Taipei, Taiwan.

Board

  • Michael N. Chang, Director since November 1998, President and Chief Executive Officer since November 1998
  • Anthony E. Altig, Director since November 2007
  • Mark Auerbach, C.P.A., Director since June 2005
  • Joseph Y. Chang, Ph.D., Director since November 1998
  • Peter E. Grebow, Ph.D., Director since February 2009
  • Alain B. Schreiber, M.D., Director since May 2001

Management

  • Michael N. Chang, Ph.D., President and Chief Executive Officer
  • Kevin P. Poulos, Chief Commercial Officer
  • Tessie M. Che, Ph.D., Chief Operating Officer and Senior Vice President, Corporate Affairs
  • Sherwood L. Gorbach, M.D., Chief Medical Officer and Senior Vice President, Medical Affairs
  • Francois-Xavier Frapaise, M.D., Chief Scientific Officer and Senior Vice President
  • John D. Prunty, C.P.A., Chief Financial Officer and Vice President, Finance
  • Youe-Kong Shue, Ph.D., Vice President, Clinical Development
  • Yoshi Ichikawa, Ph.D., Executive Director, Intellectual Property & Discovery
  • Pam Sears, Ph.D., Executive Director, Biology and Pre-Clinical Science
  • Mitchell Che, M.S., Executive Director, Operations and Information Technology

Pipeline Products

Fidaxomicin (OPT-80) is a novel macrocycle, which inhibits the bacterial enzyme RNA polymerase, resulting in the death of Clostridium difficile.[11] Data from the first of two Phase 3 clinical trials announced November 2008 demonstrated that fidaxomicin met the primary endpoint of being non-inferior to oral vancomycin (92.1% vs. 89.8%), met the secondary endpoint of reducing disease recurrence (13.3% vs. 24%) and also met the exploratory global cure endpoint (77.7% vs. 67.1%), defined as cure without recurrence at the end of therapy.[12] A second Phase 3 clinical trial of the same design is currently ongoing in North America and Europe. Fidaxomicin has been granted fast track status by the FDA.

Prulifloxacin is an oral prodrug fluoroquinolone antibiotic with broad-spectrum activity against gram-positive and gram-negative bacteria, including Pseudomonas aeruginosa. It is metabolized in the body to the active compound ulifloxacin (also known as AF 3013).[13][14] In 2009, Optimer announced results from two pivotal Phase 3 trials showing that prulifloxacin met the primary endpoint of significantly reduced duration of diarrhea compared to placebo, that it was generally well tolerated and had a similar safety profile compared to placebo. The median Time to Last Unformed Stool (TLUS) for patients treated with prulifloxacin in the first trial was 24 hours and 32.8 hours in the second trial, which were both significant improvements over the TLUS for placebo (p <0.0001).[5] Optimer acquired exclusive U.S. commercial rights to prulifloxacin from Nippon Shinyaku Co. in 2004.

Optimer licensed OPopS, a computer-aided technology and drug discovery platform from The Scripps Research Institute, or TSRI, in July 1999 to develop potential drug candidates through carbohydrate drug synthesis. With OPopS, the Company is able to reduce the time required for the synthesis of these molecules from weeks or months to hours.[15]

Cempra Pharmaceuticals, Inc. licensed a library of approximately 500 macrolides from Optimer in 2006 including OPT-1068, now known as CEM-101, which has demonstrated potent activity against multi-drug resistant Streptococcus pneumoniae and Streptococcus pyogenes, common respiratory tract infections pathogens.[16]

Notes

  1. ^ Louie, Thomas (2009-01). "OPT-80 Eliminates Clostridium difficile and Is Sparing of Bacteroides". Antimicrobial Agents and Chemotherapy. 535 (1): 261–263. PMID 18955523. {{cite journal}}: |access-date= requires |url= (help); Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  2. ^ Fritsche, TR (2009). "Antimicrobial activity of prulifloxacin tested against a worldwide collection of gastroenteritis-producing pathogens, including those causing traveler's diarrhea". Antimicrob Agents Chemother. 53 (3): 1221–4. PMID 19114678. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  3. ^ Giannarini, G. (2009). "Prulifloxacin: clinical studies of a broad-spectrum quinolone agent". Future Microbiol. 4 (2): 13–24. PMID 19207096. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  4. ^ Fritsche, TR (2009). "Antimicrobial activity of prulifloxacin tested against a worldwide collection of gastroenteritis-producing pathogens, including those causing traveler's diarrhea". Antimicrob Agents Chemother. 53 (3): 1221–4. PMID 19114678. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  5. ^ a b c Steffen, R. (2009-9-14), "Prulifloxacin, a New Fluoroquinolone Treatment for Traveler's Diarrhea", Presented at the 49th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, California: Interscience Conference on Antimicrobial Agents and Chemotherapy and American Society for Microbiology. {{citation}}: |access-date= requires |url= (help); Check date values in: |date= (help); Cite has empty unknown parameter: |coeditors= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: date and year (link) Poster abstract Full poster found here listed as “Prulifloxacin 002 Phase 3” Cite error: The named reference "“ICAAC" was defined multiple times with different content (see the help page).
  6. ^ Louie, Thomas (2009-01). "OPT-80 Eliminates Clostridium difficile and Is Sparing of Bacteroides". Antimicrobial Agents and Chemotherapy. 535 (1): 261–263. PMID 18955523. {{cite journal}}: |access-date= requires |url= (help); Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  7. ^ Johnson, Stuart (2009-06). "Recurrent Clostridium difficile infection: a review of risk factors, treatments, and outcomes". Journal of Infection. 58 (6): 403–410. PMID 19394704. Retrieved 2009-11-10. {{cite journal}}: Check date values in: |date= (help); Cite has empty unknown parameter: |coauthors= (help)
  8. ^ Golan, Y. (2009-09), "Low Recurrence Rate Among Patients with C. difficile Infection Treated with Fidaxomicin", ICAAC 2009, San Francisco, California: Interscience Conference on Antimicrobial Agents and Chemotherapy, retrieved 2009-11-09 {{citation}}: Check date values in: |date= (help); Cite has empty unknown parameter: |coeditors= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: date and year (link)
  9. ^ Gorbach, S. (2009-09), "Safety of Fidaxomicin Versus Vancomycin in Treatment of Clostridium difficile Infection", ICAAC 2009, San Francisco, California: Interscience Conference on Antimicrobial Agents and Chemotherapy and American Society for Microbiology, retrieved 2009-11-09 {{citation}}: Check date values in: |date= (help); Cite has empty unknown parameter: |coeditors= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: date and year (link)
  10. ^ ClinicalTrials.gov
  11. ^ Netterwald, James (2009-01-01). "Mapping Targets to Discovery". Drug Discovery & Development. Advantage Business Media. Retrieved 2009-11-09. {{cite news}}: Cite has empty unknown parameter: |coauthors= (help)
  12. ^ Louie, T.J. (2009-05-17), "A randomized, double-blind clinical trial of OPT-80 versus vancomycin in Clostridium difficile infection", European Congress of Clinical Microbiology and Infectious Diseases, Helsinki, Finland, retrieved 2009-11-09 {{citation}}: Cite has empty unknown parameter: |coeditors= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: date and year (link) CS1 maint: location missing publisher (link)
  13. ^ Fritsche, TR (2009). "Antimicrobial activity of prulifloxacin tested against a worldwide collection of gastroenteritis-producing pathogens, including those causing traveler's diarrhea". Antimicrob Agents Chemother. 53 (3): 1221–4. PMID 19114678. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  14. ^ Giannarini, G. (2009). "Prulifloxacin: clinical studies of a broad-spectrum quinolone agent". Future Microbiol. 4 (2): 13–24. PMID 19207096. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  15. ^ Borman, Stu (2004-08-09). "Carbohydrate Vaccines". Chemical & Engineering News. American Chemical Society. pp. 31–35. Retrieved 2009-11-10. {{cite news}}: Cite has empty unknown parameter: |coauthors= (help)
  16. ^ McGhee, P (2009-11). "In Vitro Activity of CEM-101 Against Streptococcus Pneumoniae and Streptococcus Pyogenes with Defined Macrolide Resistance Mechanisms". Antimicrobial Agents and Chemotherapy. 53 (11). PMID 19884376. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)

KDR 23:53, 1 October 2009 (UTC)

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