Shares in Depomed Inc. on Friday gained nearly 10 percent on news that the FDA approved Proquin XR, a once-daily, extended-release formulation of ciprofloxacin hydrochloride that the specialty pharmaceutical company soon plans to partner.
"This is clearly a momentous moment for us," Bret Berner, Depomed's vice president of product development, told BioWorld Today. The approval marks the company's first regulatory authorization, and while he declined to provide details of the pending partnering plans, he added that the antibiotic's launch is planned by the end of the year.
Indicated for the treatment of uncomplicated urinary tract infections (UTIs), Proquin XR's efficacy is being touted by Depomed as superior to drugs from the same class. Preliminary analysis of a randomized, double-blinded Phase III trial of 1,037 patients showed that Proquin XR eradicated 93.4 percent of the bacteria most commonly responsible for causing UTIs, a comparable rate to the 89.6 percent seen in patients on twice-daily Cipro (ciprofloxacin, Bayer AG).
The Menlo Park, Calif.-based company, whose stock (NASDAQ:DEPO) gained 40 cents following news of the approval to close at $4.47, also highlighted Proquin XR's side-effect profile as setting it apart from other drugs in the same space. Studies have shown that it causes fewer incidences of gastrointestinal side effects, including nausea and diarrhea, than alternative versions of ciprofloxacin. In fact, Depomed said its product represents the first ciprofloxacin formulation with nausea and diarrhea listed as uncommon adverse events in its label rather than common.
"Nausea and diarrhea are known to be major reasons for the discontinuation of therapy on ciprofloxacin," Berner said. "They also are the No. 1 and 2 reasons for call-backs to physicians."
In the Phase III study, overall gastrointestinal disorders were reported in 2.9 percent of Proquin XR patients and 5.1 percent of Cipro patients. Also, there were fivefold fewer complaints of nausea and sevenfold fewer cases of diarrhea reported in the Proquin XR group, compared to Cipro patients.
The company attributed Proquin XR's side-effect profile to the underlying technology used in creating the extended-release formulation. The Gastric Retention (GR) system oral drug delivery technology, designed for drugs that are preferentially absorbed high in the gastrointestinal tract, swells following ingestion and is retained in the stomach for a number of hours while it continuously releases the incorporated drug at a controlled rate to absorption sites in the upper intestinal tract.
"We've always claimed that we could do [positive] things with gastrointestinal side effects," Berner said. "And for future products, this is going to be very important."
Proquin XR gradually releases the drug over six hours, stopping large quantities of the active ingredient from quickly entering a patient's intestinal system. In contrast, Depomed conducted dissolution studies that showed that Cipro and generic equivalents release their entire dosage within about 30 minutes. Even once-daily Cipro XR's two-hour release is far quicker than Proquin XR, which produces common side effects that include vaginal yeast infections and headaches, DepoMed said.
Proquin XR, approved after four years of in-house development, is indicated for a 500-mg dose over a three-day course of treatment. Its new drug application, submitted last summer, was based largely on the aforementioned Phase III trial. (See BioWorld Today, July 21, 2004.)
The ciprofloxacin market is estimated at $1.5 billion in the U.S., the company said, adding that prescriptions for uncomplicated UTIs representing a significant portion of usage. To tap overseas markets, Depomed is in the midst of partnering talks to cover European and Asian territories, said Sylvia Wheeler, its senior director of corporate communications. She added that the company also is contemplating additional applications of the drug to eventually expand its marketability.
"Ciprofloxacin certainly is used for many different complications," Berner said, adding that Depomed is "considering doing some trials" that would be required for a label expansion.
Beyond its excitement over the Proquin XR approval, the company also has high hopes for another product borne of its internal development activities, Glumetza (metformin GR). Depomed expects an FDA decision by June 7 on a marketing application for the Type II diabetes drug, which also was developed with the GR system, following an approvable letter issued earlier this spring. That letter indicated that Glumetza is approvable pending discussions related to finalizing a single manufacturing specification. Partnered with Biovail Corp., of Toronto, the drug also is under regulatory review in Canada. Biovail will market the product there and is expected to sublicense its U.S. rights to another partner later this year. (See BioWorld Today, March 2, 2005.)
Those near-term prospects offered by Proquin XR and Glumetza have Depomed well on its way to generating its initial product revenues. And in its pipeline, the company, which looks to off-patent drugs or those soon losing patent protection for reformulation development, is conducting a Phase II trial of Gabapentin GR in post herpetic neuralgia patients.