Indevus Pharmaceuticals Inc. heard from Aventis SA that the pharmaceutical company will not exercise its option on pagoclone, officially clearing the deck for Indevus to seek a new partner for its anti-anxiety agent.
Aventis was a chance for pagoclone to remain partnered following the decision by Pfizer Inc., of New York, to return all rights to Indevus, of Lexington, Mass., in June.
"[Aventis] had a contractual right to look at the drug and it decided within its option period that it didn't want to take [pagoclone] on," said William Boni, vice president of corporate communications at Indevus.
Had Aventis, of Strasbourg, France, picked up the option, it would have completed a licensing circle of sorts. Indevus, back when it was still named Interneuron Pharmaceutics Inc., in-licensed pagoclone from Rhone-Poulenc Rorer. Indevus took the product through Phase II trials and then licensed it to Warner-Lambert Co. in a deal potentially worth about $74 million. Warner-Lambert merged with Pfizer, and Pfizer "took [pagoclone] into clinical testing and remained pretty enthusiastic about it," Boni said, until Pfizer's announcement in June that it no longer wished to participate, following studies that missed their endpoints. (See BioWorld Today, Dec. 28, 1999, and June 10, 2002.)
Pfizer, Boni said, "conducted trials in general anxiety and panic disorder, two of which did not reach the level of efficacy seen in previous testing." Overall, six clinical trials have been conducted with pagoclone in generalized anxiety disorder and panic disorder.
"There were a number of Phase III trials done," he told BioWorld Today. "We are looking at some very interesting data and are examining the parameters of the trials that were conducted, including the ones that didn't reach statistical efficacy."
Pagoclone is a member of the cyclopyrrolone class of compounds. It acts as a gamma amino butyric acid (GABA) receptor modulator. The product is designed to increase the action of GABA and thus reduce excess neuronal activity and alleviate the symptoms of panic and anxiety. What is needed for pagoclone approval, Boni said, is a Phase III program.
"The extent of that program is undefined," he said. "But based on the data that we have seen, it remains an attractive asset for us, most likely to partner out." Boni added that Indevus is "pursuing contacts with a number of large pharmaceutical companies," but he wouldn't speculate as to when a deal might be signed.
But pagoclone rides shotgun to Indevus' main product - trospium - anyway.
"That is our lead product and that was our lead all the way along," Boni said. In June the company said it completed enrollment in a 12-week, double-blind, placebo-controlled, 524-patient Phase III trial with trospium in overactive bladder patients. The trial's primary endpoints compare the reduction in frequency of urination and the reduction in incontinence episodes among trospium-treated patients to placebo patients. Boni said Indevus expects data in late September or early October. The company then would be expected, with positive data, to move forward with an NDA, he said.
Indevus had $46.2 million in cash, cash equivalents and marketable securities as of June 30. It posted a net loss for its fiscal third quarter of about $6 million. The decision by Aventis not to pick up pagoclone might not be that noteworthy, Boni said, other than solidifying the notion that Indevus has complete control of the product.
"The option was something that was there," Boni said.
Indevus' stock (NASDAQ:IDEV) fell 20 cents Friday, or 11.2 percent, to close at $1.59.