Indevus Pharmaceuticals Inc. took another step toward an approved product for overactive bladder by filing a new drug application for trospium chloride.
The company also reported new trospium Phase III data at the American Urological Association meeting in Chicago. However, having divulged in September the meatiest parts of the Phase III trial that hit both primary and secondary endpoints, the data presented at the meeting basically were "all the efficacy data and the adverse event data," said William Boni, vice president of corporate communications at Lexington, Mass.-based Indevus. (See BioWorld Today, Sept. 25, 2002.)
Trospium is an in-licensed product and approved in Europe, allowing Indevus to add European data to the filing. The NDA includes results from 32 clinical studies that involved more than 2,700 individuals.
"All the European data is part of the NDA package," Boni told BioWorld Today.
In the Phase III, trospium hit endpoints of reduction in frequency of urination and reduction in number of urge incontinent episodes. Also, the severity of urgency was reduced. Assuming a general review time of 12 months, Boni said Indevus would be "pleased if we were in a position to launch in the middle of next year."
As of now, the product is unpartnered, but "discussions are active," Boni said, adding that Indevus is "speaking with several potential partners and discussing a variety of business models."
"Our target is to have someone on board this year," he said.
Trospium, a muscarinic receptor antagonist, is designed to relax smooth muscle tissue in the bladder and thereby decrease bladder contractions. Indevus licensed the U.S. rights to the product from Madaus AG, of Köln, Germany, in 1999, back when Indevus was still called Interneuron Pharmaceuticals Inc. The twice-daily formulation for which it filed might be just the beginning.
"We are working on a once-a-day form with Shire [Pharmaceuticals Group plc]," Boni said, "which should have completed its development process and be ready to launch about two to three years after the launch of the twice-a-day."
The Shire deal was signed in March.
The overactive bladder market in the U.S. is estimated to be near $1 billion annually and growing, but it's a market characterized by dissatisfaction. Side effects cause many patients to discontinue therapy after six months, Indevus said. Given that overactive bladder is a chronic condition, it would appear that the estimated 17 million overactive bladder sufferers in the U.S. would take to a new product with less severe side effects, the most notable of which is "fairly intense dry mouth," Boni said.
In placebo-controlled trospium studies, 17.4 percent of trospium patients experienced dry mouth, and 5.2 percent experienced constipation. In Indevus' Phase III trial, dry mouth was reported in 21.8 percent of trospium patients; constipation was reported in 9.5 percent.
When considering the competition, Boni said, "We think our dry mouth rate is highly competitive."
Behind trospium, Indevus has pagoclone, an anti-anxiety product. The product has been in numerous trials and has had a bumpy clinical road, causing Pfizer Inc., of New York, to return rights to the product in June. Aventis SA, of Lyon, France, had an option on rights but did not pick it up. It remains unpartnered and Boni said Indevus is "still seeking a partner to bring pagoclone forward in a full-blown Phase III development program." (See BioWorld Today, June 10, 2002, and Sept. 3, 2002.)
There have been other Indevus drug miscues. The heart failure product Bextra, which was being developed in a joint venture called CPEC LLC with Incara Pharmaceuticals Corp., of Research Triangle Park, N.C., in 1999 stumbled in a Phase III trial when a data and safety monitoring board recommended it be stopped due to seeing no significant survival advantage. The neuroprotective drug CerAxon failed in a Phase III trial in moderate to severe ischemic stroke in 2000. But those events fade into the background as the company now eyes trospium's potential approval. (See BioWorld Today, July 30, 1999, and Jan. 11, 2000.)
"This is a major milestone for the company," Boni said. "The fact is, we have a very valuable asset now and the next step will be to make sure that asset is a commercial success."
Indevus' stock (NASDAQ:IDEV) gained 7 cents Monday to close at $3.94.