Parkinson's Combo Drug (Numient) Gets Go Ahead in Europe

Pauline Anderson

Disclosures

September 25, 2015

The European Committee for Medicinal Products for Human Use (CHMP) has recommended granting marketing authorization for IPX066 (Numient, Impax Laboratories), a modified-release oral capsule formulation of levodopa-carbidopa, for the treatment of Parkinson's disease (PD).

The indication is for the symptomatic treatment of adult patients with PD, a statement from the European Medicines Agency (EMA) released today notes. This formulation was approved by the US Food and Drug Administration in January of this year under the brand name Rytary.

Numient will be available in Europe as 95 mg/23.75 mg, 145 mg/36.25 mg, 195 mg/48.75 mg, and 245 mg/61.25 mg modified-release capsules.

"A benefit of Numient is its ability to improve motor symptoms in patients with early or advanced forms of PD," the EMA release said.

The CHMP's positive opinion is based on results from three phase 3 trials investigating the safety and efficacy of this formulation in patients with early (levodopa-naive) and advanced PD in the United States and in Europe.

APEX-PD enrolled and randomly assigned 381 levodopa-naive patients. The study met its primary efficacy endpoint of mean change from baseline in the sum of Unified Parkinson's Disease Rating Scale (UPDRS) Part II (activities of daily living) score and UPDRS Part III (motor examination) score for the combination vs placebo at end of study.

In ADVANCE-PD a trial of 393 randomly assigned patients with advanced PD having "off" time, results showed treatment with IPX066 reduced the percentage of "off" time (36.9% to 23.8%) from baseline vs immediate-release levodopa-carbidopa (36.0% to 29.8%) during waking hours to end of study, representing almost 1.2 hours of additional "off" time improvement, a company release notes. IPX066 also increased "on" time without troublesome dyskinesia during waking hours by 1.9 hours compared with an increase of 0.8 hours following treatment with immediate-release levodopa-carbidopa. Less "off" time was primarily related to more "on" time without troublesome dyskinesia.

In ASCEND-PD, a trial of 91 randomly assigned patients with advanced PD having "off" time, compared IPX066 vs levodopa-carbidopa plus entacapone (LCE). Patients entered the study with a baseline "off" time of 36.1% (5.9 hours) and at the end of the randomized IPX066 treatment phase, patients had "off" time of 24.0% (3.8 hours) during waking hours compared with 32.5% (5.2 hours) for LCE (P < .0001), representing 1.4 hours of additional "off" time improvement.

The most frequently reported adverse reactions in the 978 patients exposed to the treatment during the entire clinical program were nausea, occurring in approximately 12% of all patients; dizziness, headache, and dyskinesia, each occurring in approximately 8% of all patients; and insomnia, occurring in approximately 6% of all patients. Serious events of gastrointestinal hemorrhage and of allergic edema were "uncommon" but reported in the clinical studies with this formulation, the company release notes.

This product is not for use in patients with hypersensitivity to the active drug substances or excipients in it, narrow-angle glaucoma, pheochromocytoma, a previous history of neuroleptic malignant syndrome and/or nontraumatic rhabdomyolysis, or in patients using nonselective monoamine oxidase inhibitors , which must be discontinued 2 weeks before use of IPX066 begins, the Impax release notes.

Detailed recommendations for the use of this product will be described in the summary of product characteristics, which will be published in the European public assessment report, the EMA statement said. The report will be made available in all official European Union languages after the European Commission grants marketing authorization.

"The positive opinion from the CHMP recommending the approval of Numient is a significant step forward to providing a new treatment option to patients in Europe suffering from Parkinson's disease," said Fred Wilkinson, president and chief executive officer of Impax in the company release. "We are committed to realizing the full potential of this important franchise and we look forward to the European Commission's decision in the coming months.

"We continue to have discussions with potential partners to help commercialize Numient in Europe. If approved, we will work quickly to bring Numient to patients," he said.

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