UCB Launches Neupro® in the U.S. to treat Parkinson's Disease and Restless Legs Syndrome
Brussels, Belgium and Atlanta, GA – July 16, 2012 – UCB announced today that Neupro® (Rotigotine Transdermal System) is now available in U.S. pharmacies. Neupro® was approved by the U.S Food and Drug Administration in April to treat the signs and symptoms of early and advanced stage idiopathic Parkinson's disease and moderate-to-severe primary Restless Legs Syndrome.
Neupro® improves motor function and activities of daily living in patients with PD and provides effective symptom relief for patients with Restless Legs Syndrome (RLS). Neupro® is a once-daily patch that provides continuous delivery of the dopamine agonist rotigotine for 24 hours.
Over 100,000 patients have been treated with Neupro® worldwide, and seven clinical trials for the approved indications have demonstrated efficacy, safety and tolerability.
"The availability of Neupro® is an important step forward for U.S. patients living with Parkinson's disease and Restless Legs Syndrome," said Roch Doliveux, Chief Executive Officer, UCB. "UCB is dedicated to delivering innovative medicines like the Neupro® transdermal patch to people living with serious illnesses such as Parkinson's disease and Restless Legs Syndrome, by combining the latest science and technology with our researchers' insights on the holistic needs of patients."
One million Americans are currently living with PD. The cardinal motor symptoms of PD include stiffness, tremors, slow movements and postural instability. These symptoms can have a broad impact on patients' lives.
Restless Legs Syndrome may affect up to 23 million Americans. Patients with RLS often experience uncomfortable sensations in the legs, feet, arms, torso or head that typically occur during periods of rest and inactivity. Symptoms occur predominantly at night, but may emerge at any point in the day or night. Unmanaged moderate-to-severe RLS, in which patients experience symptoms two or more times a week, can be particularly disruptive for patients.
"Parkinson's disease and Restless Legs Syndrome are serious, neurological diseases," said Dr. Joseph Jankovic, Professor of Neurology and Director, Parkinson's Disease Center and Movement Disorders Clinic, Baylor College of Medicine, Houston, Texas. "The often unpredictable, debilitating nature of these diseases can require consistent, sustained symptom control throughout the day and night."
Data Demonstrated Significant Symptom Improvement for Parkinson's Disease and Restless Legs Syndrome
The effectiveness of rotigotine in the treatment of the signs and symptoms of idiopathic PD was established in five parallel group, randomized, double-blind placebo-controlled trials conducted in the U.S. and abroad. Depending on trial design, PD patients underwent a weekly titration of rotigotine in 2 mg/24 hours increments to either the randomized dose or optimal dose.
Three early PD trials used the Unified Parkinson's Disease Rating Scale (UPDRS), a multi-item, four-part rating scale commonly used in PD trials. Parts II and III of the UPDRS were combined to measure improvement or worsening of activities of daily living (ADL) and motor performance. Parts II and III contain 13 questions that allow clinicians to evaluate aspects of ADL—such as speech, dressing, and cutting food with utensils—and 27 questions related to the cardinal motor symptoms in PD patients, tremor, rigidity, bradykinesia, and postural instability. The trials showed rotigotine was effective in helping to improve movement and function, versus placebo, in patients with early PD.
Two trials of rotigotine in patients with advanced PD examined change from baseline in "off" time, periods when the effectiveness of medication wears off and PD symptoms return. Statistically significant reductions in off-times were observed in advanced PD patients receiving rotigotine compared with those who received placebo.
The efficacy of rotigotine in the treatment of RLS was primarily evaluated in two fixed-dose, randomized, double-blind, placebo-controlled trials with six-month maintenance periods. Patients received rotigotine doses ranging from 0.5 mg/24 hours to 3 mg/24 hours, or placebo, once daily. In these trials, rotigotine provided significant RLS symptom improvement versus placebo for RLS patients, as measured by two widely-accepted tools that allowed patients and clinicians to assess and rank symptom improvement.
The International RLS Study (IRLS) Group rating scale contains 10 items that ask the patient to assess on a scale of zero to 40, with zero being absence of RLS symptoms and 40 being most severe, the severity of sensory and motor symptoms, sleep disturbance, daytime somnolence, and impact on activities of daily living and mood associated with RLS. The Clinical Global Impression - Improvement scale, or CGI-I, allows the healthcare provider to assess how much the patient's illness has improved or worsened compared to a baseline state established at the beginning of the trial. The scale ranges from 1, very much improved, to 7, very much worse.
In clinical trials, the most common adverse reactions (≥5% greater than placebo) for the highest recommended doses of Neupro® for treatment of Parkinson's disease were nausea, vomiting, somnolence, application site reactions, dizziness, anorexia, hyperhidrosis, insomnia, peripheral edema, and dyskinesia. The most common adverse reactions (≥5% greater than placebo) for the highest recommended dose of Neupro® for treatment of Restless Legs Syndrome were application site reactions, nausea, somnolence, and headache.
Neupro® is available in four different dosage strengths for the signs and symptoms of Parkinson's disease (2 mg/24 hours, 4 mg/24 hours, 6 mg/24 hours, and 8 mg/24 hours). For moderate-to-severe primary RLS, dosing is available in three different dosage strengths (1 mg/24 hours, 2 mg/24 hours, and 3 mg/24 hours).
About Parkinson's disease
Parkinson's disease develops with the loss of nerve cells in the brain that produce a chemical called dopamine. The symptoms of PD include both motor and other system involvement and can have a broad impact on patients. As dopamine levels fall, movement (motor) symptoms—tremors (uncontrollable shaking), rigidity (stiffness or muscle tensing) and bradykinesia (slowness and loss of spontaneous movement)—can progress, along with other underlying symptoms of PD.
About Restless Legs Syndrome
RLS is characterized by unpleasant sensations in the legs and an uncontrollable urge to move to gain relief. Most people with RLS have difficulty falling asleep and staying asleep.
Studies have shown that many patients with RLS may also experience symptoms during the day. Daytime symptoms of RLS, such as inability to sit still and involuntary leg jerks, are increasingly recognized. RLS can result in exhaustion and daytime fatigue, and may affect daily activities. Patients with moderate-to-severe RLS may require long-term treatment for their RLS.
While the underlying pathophysiology of RLS is not fully understood, it is thought to involve central dopamine systems. Recent neuroimaging data suggest that RLS patients may carry an abnormality in dopamine transport that can be visualized both day and night.
About Neupro® in the U.S.
Neupro® (Rotigotine Transdermal System) is indicated for the treatment of the signs and symptoms of idiopathic Parkinson's disease and moderate-to-severe primary Restless Legs Syndrome (RLS). For more information about Neupro visit www.neupro.com.
Neupro® in the U.S. Important Safety Information
Neupro® contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life threatening or less severe asthmatic episodes in certain susceptible people.
Patients treated with Neupro® have reported falling asleep while engaged in activities of daily living and somnolence. In clinical trials for the highest recommended Neupro® dose, the incidence of the treatment difference between Neupro® and placebo for somnolence was 16% for early-stage Parkinson's disease, 4% for advanced-stage Parkinson's disease, and 6% for Restless Legs Syndrome. Some patients perceived no warnings signs, such as excessive drowsiness. Patients should be advised to exercise caution while driving, operating heavy machinery or working at heights during treatment with Neupro®.
There is an increased risk for hallucinations in patients with advanced-stage Parkinson's disease treated with Neupro®. In clinical trials for the highest recommended Neupro® dose, the incidence of the treatment difference between Neupro® and placebo for hallucinations was 4%, and this difference increased with increasing dose. Patients also may experience new or worsening mental status and behavioral changes, which may be severe, including psychotic-like behavior during Neupro® treatment or after starting or increasing the dose of Neupro®.
Neupro® may cause symptomatic postural/orthostatic hypotension and syncope, especially during dose escalation, elevated blood pressure, elevated heart rate, weight gain and fluid retention. Neupro® should be used with caution in patients with severe cardiovascular disease.
Case reports suggest that patients can experience intense urges to gamble, increased sexual urges, intense urges to spend money, binge eating, and other intense urges, and the inability to control these urges while taking medications, including Neupro®, that increase central dopaminergic tone and that are generally used for the treatment of Parkinson's disease. Patients should be monitored for the development of new or increased urges while being treated with Neupro®. Dose reduction or discontinuation of Neupro® should be considered if such urges develop.
Neupro® may increase the dopaminergic side effects of levodopa and may cause and/or exacerbate pre-existing dyskinesia. In clinical trials for the highest recommended Neupro® dose, the incidence of the treatment difference between Neupro® and placebo for dyskinesia was 7% for advanced-stage Parkinson's disease, and this difference increased with increasing dose.
Neupro® can cause application site reactions, and some may be severe. In clinical trials for the highest recommended Neupro® dose, the incidence of the treatment difference between Neupro® and placebo for application site reactions was 15% for early-stage Parkinson's disease, 23% for advanced-stage Parkinson's disease, and 39% for Restless Legs Syndrome. Most reactions were mild or moderate in intensity and were limited to the patch area.
Patients with Parkinson's disease have a higher risk of developing melanoma than the general population. Patients should be monitored for melanomas frequently when using Neupro®.
Dopaminergic medicinal products, including Neupro®, may cause augmentation and rebound in RLS patients.
The most common adverse reactions (≥5% greater than placebo) for the highest recommended doses of Neupro® for treatment of Parkinson's disease are nausea, vomiting, somnolence, application site reactions, dizziness, anorexia, hyperhidrosis, and insomnia. The most common adverse reactions (≥5% greater than placebo) for the highest recommended dose of Neupro® for treatment of Restless Legs Syndrome are application site reactions, nausea, somnolence, and headache.
Additional important safety information for Neupro® can be accessed at www.neupro.com/pi.
About Neupro® in the European Union
Neupro® (rotigotine) is approved in the European Union for the treatment of the signs and symptoms of early-stage idiopathic Parkinson's disease, as monotherapy (i.e. without levodopa) or in combination with levodopa, i.e. over the course of the disease, through to late stages when the effect of levodopa wears off or becomes inconsistent and fluctuations of the therapeutic effect occur (end of dose or on-off fluctuations). Neupro® is also approved in the European Union for the symptomatic treatment of moderate to severe idiopathic Restless Legs Syndrome in adults.
Neupro® in the European Union Important Safety Information
Neupro® is contraindicated in case of hypersensitivity to the active substance or to any of its excipients, and in case of magnetic resonance imaging (MRI) or cardioversion. Neupro® should be removed if the patient has to undergo MRI or cardioversion to avoid skin burns.
It is recommended to monitor blood pressure, especially at the beginning of treatment, due to the risk of postural/orthostatic hypotension associated with dopaminergic therapy and reported during Neupro® treatment. Neupro® has been associated with somnolence and episodes of sudden sleep onset. Patients treated with dopamine agonists including Neupro®, have been reported pathological gambling, increased libido and hypersexuality. Symptoms suggestive of neuroleptic malignant syndrome have been reported with abrupt withdrawal of dopaminergic therapy. Therefore it is recommended to taper treatment.
Hallucinations have been reported, and patients should be informed that hallucinations can occur.
Cases of cardiopulmonary fibrotic complications have been reported in some patients treated with ergot-derived dopaminergic agents. Neuroleptics given as antiemetic should not be given to patients taking dopamine agonists. Ophthalmologic monitoring is recommended at regular intervals or if vision abnormalities occur.
External heat, from any source should not be applied to the area of the patch. Exposure of a skin rash or irritation to direct sunlight could lead to changes in the skin color. If a generalized skin reaction (e.g. allergic rash) associated with the use of Neupro® is observed, Neupro® should be discontinued.
Caution is advised when treating patients with severe hepatic impairment or acute worsening of renal function, a dose reduction might be needed.
The incidence of some dopaminergic adverse events, such as hallucinations, dyskinesia, and peripheral oedema generally is higher when given in combination with L-dopa. This should be considered when prescribing Neupro®.
Neupro® contains sodium metabisulphite, a sulphite that may cause allergic-type reactions including anaphylactic symptoms and life threatening or less severe asthmatic episodes in certain susceptible people.
Neupro® should not be used during pregnancy. Breast-feeding should be discontinued.
In restless legs syndrome augmentation may occur. Augmentation refers to the earlier onset of symptoms in the evening (or even the afternoon), increase in severity of symptoms, and spread of symptoms to involve other body parts.
At the beginning of therapy, dopaminergic adverse reactions, such as nausea and vomiting, may occur. These are usually mild or moderate in intensity and transient, even if treatment is continued.
Adverse drug reactions reported in more than 10% of Parkinson's patients treated with Neupro® are nausea, vomiting, application site reactions, somnolence, dizziness and headache. The majority of these application site reactions are mild or moderate in intensity.
Adverse drug reactions reported in more than 10% of RLS patients treated with Neupro® are nausea, application site reactions, asthenic conditions (including fatigue, asthenia, malaise) and headache. The majority of these application site reactions are mild or moderate in intensity.
All Neupro® supply should be stored in a refrigerator (2o C-8oC). There is no need for patients to transport Neupro® patches in special containers and they must not be stored in a freezer compartment.
Please refer to the European Summary of Product Characteristics for full prescribing information (Revised March 2012):
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