West Coast Editor
Optimer Pharmaceuticals Inc. reaffirmed its position in the race for a better drug against increasingly common "super bug" Clostridium difficile-associated diarrhea (CDAD) with the start of another Phase III registration trial testing the antibiotic OPT-80, an RNA polymerase inhibitor.
The company's stock (NASDAQ:OPTR) closed Tuesday at $9.92, up 2 cents.
Already available for CDAD is Exton, Pa.-based ViroPharma Inc.'s Vancocin, an oral capsule formulation of vancomycin. Some clinicians are edgy, though, about oral vancomycin speeding resistance to the intravenous form.
Doctors often start therapy in milder patients with metronidazole, a widely used generic antibiotic (also marketed as Flagyl by New York-based Pfizer Inc.) not labeled for CDAD. Metronidazole is cheaper - $50 for 10 days of treatment as generic, $80 for Flagyl - than Vancocin, which costs $1,100 for 10 days.
OPT-80 kills bacteria, whereas Vancocin "just [stops] the bacteria from proliferating and lets the immune system clean it up," noted John Prunty, chief financial officer for San Diego-based Optimer. Metronidazole nails the bug, but some studies have shown a growing recurrence rate, he added.
The opportunity is large, Prunty said.
"Vancomycin has been around for over 40 years, and still effectively treats CDAD," he said, pointing to the 85 percent to 90 percent cure rate, although there is concern about vancomycin-resistant enterococci. ViroPharma said earlier in the year that Vancocin would bring in about $200 million in revenues, and "they write about 20 percent of the prescriptions in the U.S," Prunty said. "Obviously, a lot of the rest is metronidazole, which doesn't generate as much revenue."
The design of Optimer's second trial is identical to the ongoing Phase III study, and compares safety and efficacy of OPT-80 to Vancocin. Clinical cure rate at the finish of therapy is the primary endpoint, with recurrence within four weeks the secondary endpoint. About 664 CDAD patients from 100 sites in Europe and North America will be enrolled.
"We would expect to have data late this year or the first half of next year," Prunty said, and Optimer hopes to submit a new drug application for OPT-80 next year.
The firm bought back the rights to OPT-80, also known as Difimicin, in February from Par Pharmaceutical Cos. Inc., of Woodcliff Lake, N.J., paying $20 million up front with a potential $5 million milestone payment later and single-digit royalties for seven years. Earlier in the month, Optimer raised $49 million through an initial public offering. (See BioWorld Today, Feb. 12, 2007.)
Toxin-making C. difficile can thrive in the bowels of patients treated with broad-spectrum antibiotics, and the incidence and severity have increased over time, with cases cropping up in people who have not been exposed to antibiotics or hospitals. The bug 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.
OPT-80's narrow spectrum provides an advantage. "In one of our Phase IIa studies, we showed that the normal gut floor was undisturbed," Prunty said. Broad-spectrum antibiotics kill good and bad bacteria, and when the broad-spectrum therapy is taken away, "the spores grow back with a vengeance because they don't have any competing bacteria in the gut. You end up with a revolving door, treating serial CDAD patients."
In Phase IIa, OPT-80's recurrence rate was less than 6 percent. The compound also showed a 100 percent clinical cure rate at the dose - 200 mg, twice per day - being used in the Phase III trials, and a median time to diarrhea relief of three days.
"We say [dosing takes place] every 12 hours, but it does not have to be 12 hours exactly," since OPT-80 shows a long post-antibiotic effect, Prunty said. Vancocin and metronidazole both are dosed four times per day, every six hours on the dot.
At a symposium at the 17th European Congress of Clinical Microbiology and Infectious Diseases in Munich, Germany, last month, experts confirmed a new, particularly virulent strain of CDAD known as North American Phenotype 1/027. The strain has been identified in 25 states in the U.S., and produces about 20 times more of the toxins A and B, Prunty said, adding that OPT-80 has been tested against some NAP1 strains and proven effective.
Cambridge, Mass.-based Genzyme Corp. has tolevamer for CDAD, also in two Phase III studies that are expected to yield results in the second half of this year, with approval possible as early as 2009. Not an antibiotic, tolevamer binds to and removes C. difficile toxins. The product emerged from the same technology that made the polymer Renagel (sevelamer hydrochloride), a phosphate binder approved for end-stage renal disease. An out-licensed polymer-based therapy also from that platform, WelChol (colesevelam hydrochloride, Sankyo Pharma Inc.), targets cholesterol. (See BioWorld Today, April 5, 2005.)
Other approaches to CDAD include Oscient Pharmaceuticals Inc.'s Ramoplanin, global rights to which the Waltham, Mass.-based firm regained from Pfizer in early 2006. Fast-track Ramoplanin, for which the FDA also has cleared a Phase III special protocol assessment, 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.)
Salix Pharmaceuticals Ltd., of Raleigh, N.C., has trials ongoing to expand the label of Xifaxan (rifaximin) tablets 200 mg for the treatment of travelers' diarrhea caused by noninvasive E. coli.