Valeant Pharmaceuticals International intends to start enrolling patients this quarter in the first of two Phase III trials of retigabine, only a few months after adding the late-stage epilepsy drug to its neurology pipeline through the acquisition of Xcel Pharmaceuticals Inc.
A second pivotal trial is expected to begin in the fourth quarter. Both studies are included in a special protocol assessment submitted to the FDA.
Retigabine, a first-in-class epilepsy candidate designed to work as both a potassium-channel opener and a potentiator of gamma aminobutyric acid, is being developed as an adjunct therapy for partial-onset seizures, said Jeff Misakian, spokesman for the Costa Mesa, Calif.-based company.
"It's unique in the sense that is has a dual mechanism of action," he told BioWorld Today. "That could provide another treatment option for physicians."
The first study, to be conducted at multiple sites in the U.S., Mexico and South America, will evaluate daily dosing of retigabine at 1,200 mg vs. placebo to determine the drug's safety and efficacy in patients who already are taking from one to three anti-epileptic drugs. The trial's co-primary endpoints will measure the percentage change in total partial seizure frequency per four weeks from baseline to the double-blind period, as well as determine the proportion of responders who experience a 50 percent or greater reduction in seizure frequency.
The same protocol will apply to the second pivotal trial, though that study will be conducted at 60 sites in other areas of the world, and will have two retigabine treatment arms - 600 mg per day and 900 mg per day - in addition to the placebo arm.
Valeant anticipates enrolling about 800 patients altogether.
Results from a previously completed Phase II study testing three dose levels of retigabine against placebo showed statistical significance in the two higher doses. Data showed that the median monthly seizure rate decreased by 23 percent in patients receiving 600 mg per day, 29 percent in the 900-mg group, and 35 percent in the 1,200-mg group vs. a 13 percent decrease in the placebo arm. Retigabine also was found to be well tolerated, with adverse effects to the central nervous system similar to other anti-epileptic drugs, such as somnolence, dizziness, amnesia, ataxia and paresthesia.
If the Phase III studies proceed as planned, the company expects to report data during the second half of 2007, followed by the submission of a new drug application and a possible market launch in 2008.
Misakian said Xcel originally had estimated a market date in 2009, but "once we started working ourselves and got the SPA in place, 2008 seemed like a realistic time frame."
Epilepsy, which affects about 2.5 million Americans, has a global market of about $8.7 billion. Valeant said retigabine could reach more than $500 million in peak sales, a figure that could increase if the company opts to pursue additional indications.
Epilepsy drugs frequently are used off label to treat neuropathic pain, Misakian said, though Valeant has no ongoing trials for other indications and "it's still a bit early for us to think about" investigating the drug in other neurological areas.
San Diego-based Xcel acquired retigabine in February 2004 from German company Viatris GmbH & Co. A year later, that drug would become the centerpiece of Xcel's deal with Valeant. The companies closed the transaction in March, with Valeant paying $280 million. (See BioWorld Today, Feb. 4, 2005.)
Valeant's sales force increased to 200 through the Xcel acquisition and would market retigabine itself upon approval.
In addition to retigabine, Valeant's purchase of Xcel included two marketed products: the epilepsy drug Diastat, a gel formulation of diazepam that is administered in acute situations to control seizures, and Migranal, a nasal spray to alleviate migraines. Those drugs brought in revenues of about $7.3 million in March.
Valeant, which intends to post its second-quarter earnings Aug. 4, recorded a net loss of $139.3 million, or $1.57 per share, for the first quarter. As of March 31, the company had cash, cash equivalents and marketable securities totaling $361.5 million.
Shares of Valeant (NYSE:VRX) gained 56 cents Tuesday to close at $19.96.