Source: PRNewswire
Date: 10 October 2006

New Analyses Further Support Benefits of Once-Daily AZILECT(R) in the Treatment of Both Early and More Advanced Parkinson's Disease

Results Presented at the 131st American Neurological Association Meeting

KANSAS CITY, Mo., Oct. 10 /PRNewswire-FirstCall/ -- New reports of AZILECT(R) (rasagiline tablets) as initial monotherapy, AZILECT(R) as first adjunctive therapy in moderate patients, and AZILECT(R) in combination with other adjunct agents in moderate to advanced patients were presented at the American Neurological Association meeting today. This information was obtained through further analysis of the three pivotal clinical studies in more than 1,500 patients that supported the approval of AZILECT(R) for the symptomatic treatment of Parkinson's disease.

AZILECT(R) as Initial Monotherapy: Pre-specified non-motor endpoints that captured global aspects of patient improvement and treatment response in 404 patients with early Parkinson's disease in the TEMPO trial provided new insight into the effect of once-daily AZILECT(R) in that patient group. AZILECT(R)-treated patients maintained their quality-of-life scores while scores deteriorated in the placebo group. AZILECT(R) 1mg treated patients also experienced significantly more global improvement and the severity of their illness deteriorated less. "These data show that AZILECT(R) is a good choice for initial monotherapy because it is effective in helping manage early PD symptoms and is also generally well tolerated," said John Bertoni, M.D., Ph.D., Creighton University, and lead author of this abstract.

AZILECT(R) as First Adjunct Therapy in Moderate Disease: Once-daily AZILECT(R) (rasagiline tablets) has demonstrated effectiveness in reducing "OFF" time as adjunct therapy to levodopa in both the PRESTO and LARGO studies. The effect of AZILECT(R) on only patients with moderate disease was evaluated by pooling data from Parkinson's patients in the PRESTO and LARGO studies. Moderate patients were defined as those receiving only levodopa at baseline (n=253) and those with relatively "mild" fluctuations ("OFF" time defined as less than or equal to 4hr, n=217). The addition of AZILECT(R) 1mg daily in the "levodopa only" group significantly reduced "OFF" time and improved clinician's global impression, improved UPDRS-Motor score when "ON," and UPDRS-ADL when "OFF" scores versus placebo (all p < 0.005). Results for the mild fluctuator subgroup were similar, with AZILECT(R) significantly reducing "OFF" time and improving the clinician's global impression versus placebo (all p < 0.001). "It is valuable to look at subgroups, such as patients with moderate disease to determine that AZILECT(R) provides benefits to patients over a range of baseline motor-fluctuation severity, since this reflects what is seen in clinical practice," said Steven Schwid, M.D., University of Rochester. "We also looked at results across geographical areas and found that, in the PRESTO and LARGO studies, there were consistent treatment benefits seen across two geographically-separate, large-scale clinical studies of similar design."

AZILECT(R) as Adjunct Therapy; Benefits on Top of Levodopa and COMT-I: This subgroup analysis showed that once-daily AZILECT(R) as adjunct treatment produced additional symptomatic benefits when added to levodopa/carbidopa therapy and COMT inhibitors. In the 472-patient, PRESTO study, 165 patients were taking a COMT inhibitor with or without concomitant dopamine agonists. The treatment effect of AZILECT(R) at 1 mg/day compared to placebo was statistically significant in the primary endpoint of change in total daily "OFF" time and the secondary endpoint of global improvement regardless of concomitant COMT inhibitor use. "The majority of Parkinson's disease patients are on multiple medications," said Lawrence Elmer, M.D., Ph.D., University of Toledo College of Medicine. "Having a treatment that produces additional therapeutic benefit when added to other existing medications is important when taking care of patients as their disease progresses over time."

AZILECT(R) (rasagiline tablets) is indicated for the treatment of the signs and symptoms of Parkinson's disease (PD) both as initial therapy alone and to be added to levodopa later in the disease. The effectiveness of AZILECT(R) was shown in patients with early PD who were receiving AZILECT(R) as initial therapy alone and who were not receiving any other PD therapy. The effectiveness of AZILECT(R) as adjunct therapy was shown in patients with PD who were treated with levodopa.

-- Patients should not take AZILECT(R) if they currently are taking meperidine as it could possibly result in a serious reaction such as coma or death.

-- Patients should not take AZILECT(R) with tramadol, methadone, propoxyphene, dextromethorphan, St. John's wort, mirtazapine, or cyclobenzaprine.

-- Patients should not take AZILECT(R) with other monoamine oxidase inhibitors (MAOIs), amphetamines, cold remedies containing decongestants and weight-reducing preparations containing pseudoephedrine, phenylephrine, phenylpropanolamine, or ephedrine in order to avoid a possibly dangerous increase in blood pressure. Symptoms of this reaction include severe headache, blurred vision, difficulty thinking, seizures, chest pain, unexplained nausea or vomiting, or signs or symptoms of a stroke. Patients or caregivers should seek immediate medical attention if these symptoms or other unusual symptoms occur.

-- In order to prevent a possibly dangerous increase in blood pressure, patients taking AZILECT(R) should avoid foods and beverages high in tyramine content, such as aged cheeses, air-dried meats, pickled herring, yeast extract, aged red wines, tap/draft beers, sauerkraut, and soy sauce.

-- Patients taking AZILECT(R) (rasagiline tablets) should not have elective surgery requiring general anesthesia and should not receive cocaine or other local anesthesia that contains ingredients that could raise blood pressure.

-- Patients should inform their physicians if they are taking, or planning to take, any prescription or over-the-counter drugs, especially antidepressants and ciprofloxacin.

-- Patients with moderate to severe liver disease or a tumor of the adrenal gland should not take AZILECT(R).

-- All PD patients are advised to monitor for melanoma (skin cancer) frequently and see a dermatologist on a regular basis.

Side effects seen with AZILECT(R) (rasagiline tablets) alone are headache, joint pain, and indigestion; and when taken with levodopa are uncontrolled movements (dyskinesias), accidental injury, nausea, weight loss, constipation, low blood pressure when standing, joint pain, vomiting, dry mouth, rash, and sleepiness. Patients should tell their doctor about these and any other side effects they experience when taking AZILECT(R).

Parkinson's disease is a degenerative disorder of the brain. Symptoms can include tremor, stiffness, slowness of movement, and impaired balance. An estimated one million Americans have the disease, which usually affects people over the age of 60.

Teva Pharmaceutical Industries Ltd. (NASDAQ: TEVA) , headquartered in Israel, is among the top 20 pharmaceutical companies in the world. The company develops, manufactures, and markets innovative and generic human pharmaceuticals and active pharmaceutical ingredients. Over 80% percent of Teva's sales are in North America and Europe. Teva's innovative R&D focuses on developing novel drugs for diseases of the central nervous system.

Teva's U.S. innovative product marketing subsidiary, Teva Neuroscience, Inc., will promote AZILECT(R) (rasagiline tablets) in the United States. AZILECT(R) is a registered trademark of Teva Pharmaceutical Industries Ltd. See additional important information at or call 1-877-4AZILECT for electronic releases. For hardcopy releases, please see enclosed full prescribing information.

AZILECT(R) is a registered trademark of Teva Pharmaceutical Industries Ltd.

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