West Coast Editor
A day after Oscient Pharmaceuticals Inc. sublicensed commercial rights for its product Factive in Mexico to a Pfizer Inc. division, the biotech firm disclosed that a separate deal regarding the Phase III candidate Ramoplanin has been restructured with a separate Pfizer subsidiary, and global rights now belong to Oscient.
"The next step in the process is that we need to secure and enter into a longer-term source of supply [of the drug]," said Steven Rauscher, president and CEO of Waltham, Mass.-based Oscient. "We can start the Phase III program, but we do want to button that down."
Oscient’s stock (NASDAQ:OSCI) closed Wednesday at $2.05, down 20 cents.
Vicuron Pharmaceuticals Inc., of King of Prussia, Penn., had licensed Ramoplanin to Oscient for the U.S. and Canada only, but the arrangement gives Oscient full control of manufacturing, development and commercialization worldwide. In exchange, Oscient made a one-time, up-front payment to Pfizer, with more to follow upon achieving specified regulatory milestones and as royalties on net sales. Oscient also has assumed all responsibility for drug manufacture.
Royalty obligations to Vicuron have been "adjusted to reflect the elimination of Vicuron’s manufacturing responsibility," Oscient said, and Pfizer has agreed to transfer the technological know-how related to making the drug. More specifically, an 8-K filed with the SEC shows that Oscient will pay "mid-single-digit to low double-digit" royalties to Pfizer for net sales of Ramoplanin, dependent upon the territory.
Oscient has a special protocol assessment from the FDA that calls for two pivotal, non-inferiority, Phase III trials to study Ramoplanin against Clostridium difficile-associated disease (CDAD), caused by a spore-forming bacterium that causes diarrhea and colitis. (See BioWorld Today, Dec. 22, 2005.)
Each trial will enroll about 490 patients diagnosed with CDAD from centers in the U.S., Canada and other parts of the world. Each patient will be randomly assigned to one of two treatment arms, in a double-blind regimen: Ramoplanin 200 mg orally twice daily or vancomycin 125 mg orally four times daily for 10 days. The primary endpoint will be the response rate at the end of therapy. Until recently, CDAD has been problematic mainly in patients who have had recent antibiotic therapy and/or are hospitalized, but the incidence and severity of the disease have increased over time, and anecdotal cases are being reported where no antibiotic therapy or exposure to hospitals has taken place.
Proved deadly to Clostridium difficile in vitro, Ramoplanin is not absorbed systemically from the gastrointestinal tract, acting in that locale only, and could be a new method for attacking hospital-borne pathogens.
Already in the CDAD space is Exton, Pa.-based ViroPharma Inc., with Vancocin, an oral capsule formulation of vancomycin hydrochloride. ViroPharma made headlines in December by raising $150.7 million through a public offering to support business development activities and general corporate purposes, as well as to pay off a portion of the company’s debt. (See BioWorld Today, Dec. 8, 2005.)
There’s worry about oral vancomycin, though, bringing resistance to the intravenous form, which is used against more serious cases, so "most clinicians would lead off with metronitazole," a widely used generic antibiotic that is not officially approved for CDAD, "unless they had a really sick patient, where the consequence of guessing wrong would be severe," Rauscher said.
Another firm to raise money, later in December, was San Diego-based Optimer Pharmaceuticals Inc., which brought in $22.2 million in a Series D financing, after a $12 million Series C round conducted in April. Optimer is developing the Phase IIb drug PAR-101 (OPT-80), in an effort that gained the April money from Par Pharmaceutical Companies Inc., of Spring Valley, N.Y. At the same time, Par bought equity, entering a deal to develop and market the narrow-spectrum antibiotic targeting CDAD-related diarrhea, given fast-track status by the FDA. The product could be on the market in 2008. (See BioWorld Today, Dec. 15, 2005.)
A number of drugs are in development, including Cambridge, Mass.-based Genzyme Corp.’s tolevamer, a non-absorbed polymer therapy to treat C. difficile-associated diarrhea.
"That one’s probably farthest along," Rauscher said. "The notion there is that C. difficile produces a toxin, and it’s actually the toxin that produces the disease. [Tolevamer] might have some merit, although you still have to kill the bacteria. Getting all rights to Ramoplanin was "something we wanted," he said. "We had licensed it originally from [Milan, Italy-based Biosearch Italia SpA], in the U.S. and Canada," Rauscher recalled. "At that time, Biosearch Italia was intending to be a European antibiotic company, and they were licensing compounds to other companies for development in the U.S."
Dalbavancin, for example, went to Fremont, Calif.-based Versicor Inc., which in the summer of 2002 merged with Biosearch to become Vicuron, and the new company then made clear its plans to become global. Vicuron also has anidulafungin, the antifungal licensed from Indianapolis-based Eli Lilly and Co. (See BioWorld Today, Aug. 1, 2002.)
"We had a difficult time in the relationship [with the merged firm]," Rauscher said. "The manufacturing site intended to open in Southern Italy didn’t, and Vicuron actually indicated to us that they wanted to terminate our license and take the product back."
Then, in the summer of last year, Pfizer made known its plan to buy Vicuron at $29.10 per share, or about $1.9 billion. The deal closed in September, and Oscient immediately started talking with Pfizer about getting all the rights to Ramoplanin. (See BioWorld Today, June 17, 2005.)
"Pfizer’s interests were a little more compatible to us," and the arrangement went through, Rauscher said. The deal has another benefit. "All the bulk drug we have used [in trials] so far was originally manufactured by Sanofi-Aventis, under contract to Vicuron," he said. "We wanted to control our own destiny, and have a direct relationship with the manufacturers." Talks are under way.
Earlier this week, Oscient said it has sublicensed the commercialization rights to Factive (gemifloxacin mesylate) tablets in Mexico to Pfizer SA de CV, a division of New York-based Pfizer, for an up-front payment and milestones.
The FDA has approved Factive for the five-day therapy of acute bacterial exacerbations of chronic bronchitis and the seven-day treatment of mild to moderate community-acquired pneumonia, and in January the agency accepted for filing the supplemental new drug application for clearance of Factive as a five-day treatment of mild to moderate CAP.