Depomed Inc.'s new formulation of ciprofloxacin HCl achieved top-notch results in a Phase III trial of urinary tract infections.
The extended-release version - Ciprofloxacin GR - showed efficacy and fewer side effects than the approved twice-daily Cipro.
"This is indeed a momentous day for us," said John Fara, president, CEO and chairman of Depomed, in a conference call. "This is our second product that has gone through the Phase III testing and come out successful."
The first product - Metformin GR - demonstrated positive results last December in a pivotal Phase III trial in Type II diabetes. Depomed expects to file new drug applications, first for Metformin GR, then for Ciprofloxacin GR, in the second quarter.
Fara later told BioWorld Today the products could be on the market by mid-2005, assuming a 12-month review process. If approved, they would be Depomed's first marketed products.
The company's stock (NASDAQ:DEPO) rose 72 cents Thursday, or 11.2 percent, to close at $7.15.
Phase III data of Ciprofloxacin GR confirmed Phase II results by eliminating the organisms responsible for urinary tract infections. The product proved to be as effective as twice-daily Cipro, but with fewer gastrointestinal side effects, such as nausea and diarrhea.
With Cipro coming off patent, Depomed hopes to tap into a $1.7 billion worldwide market for urinary tract infections. Unlike the twice-daily Cipro, Depomed's extended-release product is dosed once a day.
"It's a superior product," Fara said. "I think in the right partner's hands it could be half of that [$1.7 billion] market."
Depomed has talked with a number of partners for some time, Fara said. He expects to complete a U.S. partnership agreement within six months. It might be expanded to cover overseas markets, or Depomed might find a separate European partner.
"We were thrilled with the results of the study," said Bret Berner, vice president of product development. "This is exactly as you want a non-inferiority trial to come out, with your product looking better."
Depomed, of Menlo Park, Calif., started the Phase III trial last June. (See BioWorld Today, June 4, 2003.)
The trial evaluated 580 patients with uncomplicated urinary tract infections. The randomized, double-blind trial was designed to evaluate a three-day treatment course of Ciprofloxacin GR at 500 mg dosed once a day with a three-day course of Cipro at 250 mg dosed twice a day. A preliminary analysis showed that Ciprofloxacin GR eradicated 93.5 percent of the organisms responsible for the infections, compared with a Cipro rate of 89.6 percent. About 2.9 percent of patients taking Ciprofloxacin GR complained of gastrointestinal disorders, compared with 5.1 percent of those taking Cipro.
"In terms of nausea, that's a threefold reduction that we saw," Berner said. "And with diarrhea, there was a sevenfold reduction."
Cipro, a drug that also is used by people worried about anthrax exposure, lost its patent protection in December. However, Bayer AG, of Leverkusen, Germany, has a pediatric extension of the patent until this summer. Depomed's business strategy is to develop products that are off patent or about to go off patent.
Ciprofloxacin GR was developed using Depomed's Gastric Retention (GR) System technology for preferential absorption in the upper intestine.
The technology fools the stomach into thinking it contains undigested food, causing it to swell, something it does naturally when retaining large objects for further digestion. The system then continuously releases the drug at a controlled rate to absorption sites, optimizing delivery and therapeutic benefits.
Urinary tract infections are bacterial infections often caused by E. coli and typically treated with antibiotics. Bayer's Cipro had $1.7 billion in worldwide sales in 2002. Bayer's extended-release version, Cipro XR, entered the market last year, but Fara said the new product still doesn't fare as well as Ciprofloxacin GR.
"We had a marked reduction in GI side effects, which Bayer did not see in their trials with their XR," Fara said. "They had comparable GI side effects to the immediate release."
In addition to Ciprofloxacin GR, Depomed's Gastric Retention System has been used to develop Metformin GR, which has completed Phase III trials in Type II diabetes. Metformin, approved in 1994 for Type II diabetes, is sold by Bristol-Myers Squibb Co., of New York, as the immediate-release Glucophage and the once-a-day Glucophage XR. Bristol-Myers had $2.5 billion in U.S. sales of the immediate-release formulation of Metformin in 2002, before the company lost marketing exclusivity. Depomed's formulation would compete with a number of generic versions of the drug. The drug is partnered with Biovail Corp., of Toronto.
Fara said that he is not aware of any other companies developing a sustained-release ciprofloxacin product, meaning the main competition for Ciprofloxacin GR would be Cipro.
"There are other antibiotics that are used, although Cipro is by far the drug of choice," he said.
Depomed also is studying the diuretic Furosemide GR in a Phase II trial and plans to begin a Phase II of the seizure and pain drug Gabapentin GR later this year.
As of Dec. 31, Depomed had cash and investments of $44.3 million. The company raised $35.75 million in a public offering last October. (See BioWorld Today, Oct. 24, 2003.)