West Coast Editor
Genzyme Corp.'s second late-stage disappointment in a week called into question tolevamer, the Clostridium difficile-toxin binder to fight diarrhea related to the bug (CDAD), put a bigger dent in the company's shares and might have encouraged competitors in the space.
In the first of two Phase III trials, the Genzyme compound failed to beat the standard prescribed oral dose of the antibiotic vancomycin.
"We don't view this [compound] as coming to market any time in the near term, but it is very important to us that we wait to see the results of the second Phase III study, that we'll have by the end of the year," said Maria Cantor, spokeswoman for the Cambridge, Mass.-based firm.
Genzyme's stock (NASDAQ:GENZ) fell $4.02 Friday to close at $60.85.
Tolevamer performed well in a Phase II trial, Cantor noted. "It has a liquid formulation [in the Phase III study], which is one of the most important differentiators," she said.
A solid form was used in Phase II, and Genzyme scientists will be evaluating whether that played a role in the differing outcomes.
Tolevamer came from the same technology that made the polymer Renagel (sevelamer hydrochloride), a phosphate binder approved for end-stage renal disease, and the out-licensed polymer-based therapy WelChol (colesevelam hydrochloride), which went to Tokyo-based Sankyo Pharma Inc. and targets cholesterol.
Two months ago, Optimer Pharmaceuticals Inc., of San Diego, started its second Phase III registration trial testing the antibiotic OPT-80, an RNA polymerase inhibitor, against the "super-bug" CDAD. Results are due late this year or the first half of next year, and Optimer hopes to submit a new drug application for OPT-80 in 2008. (See BioWorld Today, May 2, 2007.)
Optimer's stock (NASDAQ:OPTR) ended Friday at $10.20, up 22 cents.
Vancomycin, available in capsules from Exton, Pa.-based ViroPharma Inc., still gets an 85 to 90 percent cure rate, but clinicians are nervous about the oral drug boosting resistance to the intravenous form, and a search for an alternative is under way.
Therapy for milder cases of CDAD often starts with metronidazole, a widely used generic antibiotic (also marketed as Flagyl by New York-based Pfizer Inc.).
Not labeled for CDAD, it works and is cheaper, costing $50 for 10 days of treatment as generic and $80 for Flagyl, as compared to Vancocin, which costs $1,100 for 10 days.
Genzyme's PACT study, which comprises both Phase III CDAD trials, is the largest program of its kind ever conducted.
"It's also the first time that the two standards of care are being compared," Cantor said, so the full data should prove useful aside from tolevamer.
Consistent with recent published studies, high rates of CDAD recurrences showed up in PACT patients treated with either vancomycin or metronidazole, but not in patients treated with tolevamer liquid, which generally was well tolerated with no unanticipated safety concerns. Final results will be unveiled at a medical conference.
C. difficile is the main cause of diarrhea in hospitals worldwide, hitting more than 500,000 in the U.S., and more than one of every 1,000 patients admitted in Europe, especially the aged.
The bug takes hold in the bowels of patients treated with broad-spectrum antibiotics, and the incidence and severity have increased - including cases in people who have not been exposed to antibiotics or hospitals.
Another potential alternative is Oscient Pharmaceuticals Inc.'s Ramoplanin, global rights to which the Waltham, Mass.-based firm regained from Pfizer in early 2006.
Fast-track Ramoplanin, tested under a special protocol assessment deal with the FDA, acts in the gastrointestinal tract only and is not systemically absorbed. Vicuron Pharmaceuticals Inc., of King of Prussia, Penn., had licensed Ramoplanin to Oscient for the U.S. and Canada only. (See BioWorld Today, Feb. 9, 2006.)
Oscient's shares (NASDAQ:OSCI) closed Friday at $4.63, up 1 cent.
Genzyme also said last week that hylastan, its joint lubricator for osteoarthritis knee pain, failed to beat steroids in a pivotal study, but the firm is pushing hard with Synvisc-One, another compound for the same condition. (See BioWorld Today, July 6, 2007).