Chart: Fighting C. Difficile: Beyond Optimer's Fidaxomicin

Fighting C. Difficile: Beyond Optimer's Fidaxomicin
Optimer released positive data Feb. 4 from its second pivotal Phase III trial of fidaxomicin, raising hopes that hospitals will soon have a new weapon for fighting new deadly strains of Clostridium difficile, a bacterium that occurs naturally in the gut and is ordinarily benign. Problems arise, however, when antibiotics used to treat hospital-acquired infections eliminate other resident flora, allowing novel and toxic strains of C. diff to proliferate. Outbreaks of the disease, typified by diarrhea, nausea and in severe cases, colitis, sepsis and death, have made headlines in the United Kingdom and Canada. Vancomycin and metronidazole are the current standards of care, but relapse rates with those drugs are 20 to 30 percent, and resistance is a growing worry. Optimer's data shows fidaxomicin has a slightly better cure rate and much lower recurrence rate than vancomycin, though the recurrence rate is no different among patients with a severe form of C. diff infection. Are these factors enough to sway hospitals to use fidaxomicin if approved instead of vacomycin, especially if generic versions come to market? An FDA advisory committee endorsed a generic vancomycin pathway last August ('The Pink Sheet,' Aug. 10, 2009). It remains to be seen if the generic threat constrains the size and scope of an Optimer partnership, which analysts say the San Diego firm needs to sell fidaxomicin outside the U.S. There's growing interest in infectious disease, and clarity around the regulatory pathway has led to increased deal-making for antibiotics in the $300 million to $500 million range ('The Pink Sheet,' Nov. 23, 2009). But only one C. difficile-centered drug has been partnered in recent years - a dual antibody co-developed by Medarex and the University of Massachusetts Medical School - making it difficult to benchmark likely deal terms for fidaxomicin as Optimer pushes toward an NDA filing and a likely partnership. Here's a quick look at several C. diff.-targeted compounds currently in the pipeline. - Alex Lash ([email protected])
Company & Drug	Clinical Phase	Analysis
Optimer Fidaxomicin	Phase III	Positive results from two Phase III trials give Optimer leverage in partnership negotiations. Fidoxamicin is a macrocyclic and inhibits RNA polymerase.
Medarex/Massachusetts Biologic Laboratories CDA-1+CDB-1	Phase II	Medarex and the nonprofit MBL licensed the fully human MAb combination to Merck in April 2009 for $60 million upfront and up to $165 in milestones ('The Pink Sheet' DAILY, Apr. 21, 2009).
Sanofi-Aventis ACAM-CDIFF	Phase II	Sanofi gained this C. diff. vaccine when it bought Acambis in July 2008 for $549 million ('The Pink Sheet' DAILY, July 25, 2008). It is currently recruiting for a Phase II interventional trial in the UK.
Cubist CB-183,315	Phase I	Completed single and multiple ascending dose trials with this cidal lepopeptide, should begin Phase II in first half of 2010. Unpartnered.
ViroPharma NTCD	Phase I	Licensed in 2006 from Hines VA Hospital in Chicago. NTCD is a non-toxic strain of C. difficile that would repopulate a patient's GI tract after antibiotic treatment eradicates the pathogenic strain. Unpartnered. ViroPharma sells Vancocin, the branded form of vancomycin, and NTCD is in effect a brand extension, meant to be used in conjunction with Vancocin.
Romark Nitazoxanide	Phase III (terminated)	Branded as Alinia, nitazoxanide has been a commercial diarrhea treatment for more than a decade. Romark ended a Phase III trial in 2008 because of slow recruitment, according to Clinicaltrials.gov.
Genzyme Tolevamer	Phase III (terminated)	Genzyme's toxin-binding polymer did not meet its primary endpoint of noninferiority vs. vancomycin and the trial was terminated in early 2008.