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NTI-851 (Ramoplanin)

Ramoplanin™ is a glycolipodepsipeptide antibiotic that is bactericidal for many gram-positive aerobic and anaerobic bacteria, including C. difficile and has previously been evaluated in clinical development programs for both vancomycin-resistant enteroccocus (VRE) as well as the active treatment of CDI.  Ramoplanin™ has been reported to also have activity against C. difficile spores, both in vitro and in an animal model.  Recent in vitro work sponsored by Nanotherapeutics has confirmed that effect which seems to not be sporicidal per se.  The mechanism is relatively novel in that the exosporium may be the target for Ramoplanin™ binding, permitting an “ambush” type of vegetative cell killing.   The natural history of CDI, regretfully, does not end with successful treatment of the infection.  Approximately 25% of patients will experience a recurrence with higher rates among older age groups as well as increasing comorbidities.  These relapses are thought to be at least partially due to residual spores in the human gut in clinically cured patients.  Elimination of these spores could reduce relapse rates, decreasing the risk of readmission, further treatment requirements, or adverse clinical outcomes.  An innovation gap exists for a compound that can successfully reduce such relapse rates as it reduce the risk of other nosocomial infections (e.g., VRE) and add a therapeutic regimen to the current armamentarium where currently none exists.  Nanotherapeutics believes that ramoplanin, based on its relatively novel mechanism of action, non-absorbable kinetics (enhanced by dosing to non-inflamed gut mucosa) and established safety profile from prior studies would fill this innovation gap.

 

Clinical Development

NTI-851 (Ramoplanin™) is being developed for the targeted prophylaxis of recently treated patients with C. difficile infection (CDI) at high risk for infection relapse. Twelve phase 1 studies, two phase 2 studies (one in CDI and one in VRE) as well as one phase 3 study (in CDI) have been conducted by prior Ramoplanin™ sponsors.  Nanotherapeutics is now targeting a new indication for development, relapse prevention, for Ramoplanin™  and a phase 2b study is under development with first patient in scheduled for 2016.  

 

References

Freeman J, Baines SD, Jabes D, Wilcox MH. Comparison of the efficacy of ramoplanin and vancomycin in both in vitro and in vivo models of clindamycin-induced Clostridium difficile infection. The Journal of antimicrobial chemotherapy. 2005;56(4): 717-725.

McFarland LV, Surawicz CM, Rubin M, Fekety R, Elmer GW, Greenberg RN. Recurrent Clostridium difficile disease: epidemiology and clinical characteristics. Infection control and hospital epidemiology : the official journal of the Society of Hospital Epidemiologists of America. 1999;20(1): 43-50.

Barbut F, Richard A, Hamadi K, Chomette V, Burghoffer B, Petit JC. Epidemiology of recurrences or reinfections of Clostridium difficile-associated diarrhea. Journal of clinical microbiology. 2000;38(6): 2386-2388.

McFarland LV. Alternative treatments for Clostridium difficile disease: what really works? Journal of medical microbiology. 2005;54(Pt 2): 101-111.

McFarland LV, Elmer GW, Surawicz CM. Breaking the cycle: treatment strategies for 163 cases of recurrent Clostridium difficile disease. The American journal of gastroenterology. 2002;97(7): 1769-1775.

 

 

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