UCB could bring the first competitor to GlaxoSmithKline's Requip (ropinirole) for restless leg syndrome to market later this year after submitting an sNDA for Neupro (rotigotine) for RLS.

The Belgian company submitted an sNDA for Neupro, a trandsermal patch approved for early Parkinson's disease, for the RLS indication in October. A standard review would give the application an FDA action date in August 2008.

Both Neupro and Requip are dopamine agonists initially developed for Parkinson's disease. Neupro, however, is formulated as a once-daily patch designed to provide continuous drug delivery over a 24-hour period. Parksinson's patients must take Requip three times daily; RLS patients take a dose one to three hours before bed.

GSK has also been seeking to bring a longer-acting version of Requip to the market, both for Parkinson's and RLS.

The company announced Dec. 10 that its sNDA for a 24-hour Requip XL for Parkinson's had received an "approvable" letter from FDA, which came after the company and agency were not able to negotiate labeling in time to meet the user fee deadline. GSK said it expects a two-month review window following its submission of a complete response to the letter.

GSK also received an approvable letter for Requip CR , a 14-hour controlled-release version intended for the RLS indication, in August. At the time, the company said the questions raised by FDA in the letter relate to distinguishing the currently marketed formula from the controlled-release version.

UCB's sNDA is based on two studies evaluating rotigotine for the treatment of moderate-to-severe idiopathic RLS over six months. Patients treated with Neupro showed a statistically significant reduction in RLS symptoms, as evaluated by the International Restless Legs Severity Scale.

UCB has been touting the RLS indication as potentially easier to get through FDA than the original Parkinson's NDA had been. Neupro took more than two and half years to approve as FDA wrestled with concerns over adverse events like compulsive behavior and "sleep attacks" in patients taking dopamine agonists.

The company has said, however, that Neupro for RLS uses a lower dose in healthier patients, and noted a lower association with compulsive behavior in trials (¹ Pharmaceutical Approvals Monthly October 2007, p. 27).

GSK expects to file an NDA for the first non-dopaminergic RLS therapy in the third quarter, the company told an investors meeting Dec. 13. The product, a gabapentin prodrug known as GSK1838262, is licensed from XenoPort.

"The dopamine agonists have been readily accepted in the treatment of RLS," Neurosciences Development Center head Atul Pande said, but "they still leave some room for improvement."

"Chronic use of dopamine agonists has been associated with things like augmentation and compulsive behavior so we think that ['262], because it works by a different mechanism and, at least for the foreseeable future, will be the only approved non-dopaminergic treatment for Restless Legs Syndrome, will be attractive to physicians and patients from a safety side," XenoPort CEO Ronald Barrett said during a Jan. 15 call.

Barrett spoke after XenoPort announced results from a 327-patient Phase III trial of '262 that found a statistically significantly lower proportion of relapses in the treatment group (9 percent) versus the placebo group (23 percent).

"Our study design and endpoints were defined after extensive consultation with the FDA," Barrett said. "We are particularly pleased with these results in the face of the stringent relapse criteria."

"The plan is to bring the Phase III program to completion and make a regulatory filing in the third quarter of 2008, but that's not where the development in RLS is going to stop," Pande said. GSK will continue to evaluate '262 in areas like sleep dysfunction and painful symptoms related to RLS.

Approval of a next generation RLS drug could help GSK extend the life of a business in a treatment market the company helped create with the approval of Requip for the indication in 2005. Requip is slated to lose exclusivity in May 2008, bringing generic competition.

- Jessica Merrill (j.merrill@elsevier.com) and Bridget Silverman (b.silverman@elsevier.com)

Restless Leg Syndrome Market Prepares To Move As GSK, UCB Advance Drugs

More from Archive

More from Pink Sheet