PRESS RELEASE: Early Treatment With Rasagiline May Slow Parkinson's Disease Impairment
Results of 12-month study suggest benefits of early initiation of treatment.
KANSAS CITY, Mo. and TEANECK, N.J., Apr 20, 2004 /PRNewswire-FirstCall via Comtex/ -- Early initiation of a potential
new treatment for Parkinson's disease may delay the progression of impairment associated with the disease, according to
an article published in the April 2004 issue of Archives of Neurology. In the TEMPO trial, patients treated with once-
daily rasagiline 1 or 2 mg per day for 12 months showed less impairment in Parkinson's disease features than patients
whose treatment was delayed for six months.
Impairment was measured by total Unified Parkinson's Disease Rating Scale (UPDRS) score, a research tool commonly used
to measure a patient's ability to perform mental and motor tasks and activities of daily life.
The double-blind study involved 371 patients who were randomized into three treatment groups: rasagiline 2 mg per day
for 12 months, rasagiline 1 mg per day for 12 months, or delayed treatment - placebo for six months followed by
treatment with rasagiline 2 mg per day for six months. The randomized, delayed-start design was intended to help
distinguish immediate symptomatic benefits from effects on disease progression.
"The difference in UPDRS scores between the 12-month and delayed start rasagiline groups cannot wholly be explained by
rasagiline's symptomatic effect," said Andrew Siderowf, M.D., Assistant Professor of Neurology, University of
Pennsylvania and a lead researcher on the study.
Results showed treatment with rasagiline 2 mg per day for 12 months was associated with less decline as measured by the
UPDRS scores, demonstrated by a 2.29 unit smaller decline in the mean adjusted total UPDRS scores compared with
patients in the delayed-start group (p=0.013). The difference in the change from baseline for patients treated with 1
mg per day rasagiline for a full year, compared with the delayed-start group, was 1.82 units (p=0.051).
An analysis of the activities of daily living subscale of the UPDRS also demonstrated an effect in favor of the group
treated with 2 mg rasagiline for a full year, with the decline being 0.96 units less than the delayed-start group
(p=0.0053).
"A possible explanation for these results is that rasagiline may slow the progression of Parkinson's disease, but
longer duration studies are needed to confirm these findings," said Ira Shoulson, M.D., Professor of Neurology at the
University of Rochester School of Medicine and principal investigator of the TEMPO study. "This prospect, combined with
our previous findings of benefit and safety (A Controlled Trial of Rasagiline in Early Parkinson's Disease: The TEMPO
Study, Arch Neurol 2002;59:1937-1943) suggests that rasagiline has the potential to be a promising new treatment for
PD."
The initial 26-week phase of the TEMPO trial (TVP-1012) in the Early Monotherapy in Parkinson's disease Out-patients)
showed that patients who received rasagiline 1 or 2 mg once-daily had better symptom control than those receiving
placebo. The entire 12-month study was conducted by the PSG at 32 sites in the United States and Canada.
Rasagiline was well tolerated in the study. The most commonly observed adverse events in the active treatment phase
(occurring in more than five percent of patients) were infection, headache, dizziness, and accidental injury. None of
these adverse events occurred significantly more frequently in patients originally assigned to rasagiline than in those
originally assigned to placebo.
Rasagiline is a novel, potent, second-generation, selective, irreversible monoamine oxidase type-B (MAO-B) inhibitor
that blocks the breakdown of dopamine, a substance in the brain needed to facilitate movement. A new drug application
for rasagiline for the treatment of Parkinson's disease was submitted to the U.S. Food and Drug Administration (FDA)
Sept. 5, 2003. Indications are being sought for once-daily rasagiline as a monotherapy in early Parkinson's disease and
as an adjunct to levodopa in moderate to advanced disease.
"We are excited about the possibility of marketing a treatment for Parkinson's disease that offers the ease of once-
daily dosing and is well tolerated," said Larry Downey, president of Teva Neuroscience. "The TEMPO 12-month data
suggest the potential of rasagiline to slow PD-related impairment, and we are encouraged by these findings."
Parkinson's disease is a degenerative disorder of the central nervous system. Symptoms can include tremors, stiffness,
slowness of movement, and impaired balance. An estimated one million North Americans have the disease, which usually
affects people over the age of 50.
The PSG (www.Parkinson-Study-Group.org) is an independent, non-profit consortium of Parkinson's disease investigators
from medical centers in the United States and Canada who are committed to improving treatment for persons affected by
Parkinson's disease.
The development of rasagiline is part of a long-term alliance for co-development in Parkinson's disease and European
marketing between Teva and H. Lundbeck A/S. Rasagiline was developed cooperatively by Teva and the Technion - Israel
Institute of Technology.
Teva submitted an application to market rasagiline as a treatment for PD with the European Agency for Evaluation of
Medicinal Products (EMEA) on Oct. 10, 2003. Rasagiline was also submitted for review in Canada Sept. 24, 2003 where,
upon approval, it will be marketed by Teva Neuroscience, Inc.
Teva Neuroscience, Inc. and Eisai Inc. will co-promote rasagiline in the United States, once approved by the FDA, as
part of a long-term strategic alliance between Teva Pharmaceutical Industries Ltd. and Eisai Co., Ltd.
Teva Pharmaceutical Industries Ltd. (Nasdaq: TEVA), headquartered in Israel, is among the top 30 pharmaceutical
companies in the world. The company develops, manufactures, and markets generic and branded human pharmaceuticals and
active pharmaceutical ingredients. Close to 90 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.
Eisai Inc. is a U.S. pharmaceutical subsidiary of Eisai Co., Ltd., a research-based human health care (hhc) company
that discovers, develops, and markets products in more than 30 countries. Established in 1995, Eisai Inc. began
marketing its first product in the United States in 1997 and has rapidly grown to become an integrated pharmaceutical
business with sales of nearly $1.5 billion in fiscal year 2002 (year ending March 31, 2003). Eisai focuses its efforts
in four therapeutic areas: neurology, gastrointestinal disorders, oncology, and acute care.
Safe Harbor Statement under the U.S. Private Securities Litigation Reform Act of 1995: This release contains forward-
looking statements, which express the current beliefs and expectations of management. Such statements are based on
current expectations and involve a number of known and unknown risks and uncertainties that could cause Teva's and
Eisai's future results, performance or achievements to differ significantly from the results, performance or
achievements expressed or implied by such forward-looking statements. Important factors that could cause or contribute
to such differences include Teva's and Eisai's ability to successfully develop and commercialize additional
pharmaceutical products, the introduction of competitive generic products, the impact of competition from brand-name
companies that sell their own generic products or successfully extend the exclusivity period of their branded products,
Teva's and Eisai's ability to rapidly integrate the operations of acquired businesses, the availability of product
liability coverage in the current insurance market, the impact of pharmaceutical industry regulation and pending
legislation that could affect the pharmaceutical industry, the difficulty of predicting U.S. Food and Drug
Administration ("FDA") and other regulatory authority approvals, the regulatory environment and changes in the health
policies and structure of various countries, acceptance and demand for new pharmaceutical products and new therapies,
uncertainties regarding market acceptance of innovative products newly launched, currently being sold or in
development, the impact of restructuring of clients, reliance on strategic alliances, exposure to product liability
claims, dependence on patent and other protections for innovative products, fluctuations in currency, exchange and
interest rates, operating results and other factors that are discussed in Teva's Annual Report on Form 20-F and its
other filings with the U.S. Securities and Exchange Commission ("SEC"). Forward-looking statements speak only as of the
date on which they are made, and the Company undertakes no obligation to update publicly or revise any forward-looking
statement, whether as a result of new information, future developments or otherwise.
SOURCE Teva Neuroscience, Inc.
CONTACT:
Marie Jennings of Fleishman-Hillard,
+1-816-512-2430,
[log in to unmask]
Judee Shuler of Eisai Inc.,
+1-201-287-2241
[log in to unmask]
URL:
http://www.prnewswire.com
SOURCE: PR Newswire / Macro*World Investor
http://www.mworld.com/m/m.w?lp=GetStory&id=92046201
* * *
ARTICLE: Early Treatment with Rasagiline Better than 6-Month Delay in Parkinson's Disease, Results in Less Functional
Decline
A DGReview of :"A controlled, randomized, delayed-start study of rasagiline in early Parkinson disease"
Archives of Neurology
04/20/2004
By Elda Hauschildt
Patients with early Parkinson's disease who are treated with rasagiline show less functional decline at 12 months than
do those patients whose treatment is delayed for 6 months, say researchers.
Andrew Siderowf, MD, of the Parkinson's Disease and Movement Disorders Center, University of Philadelphia,
Pennsylvania, United States, and colleagues undertook a double-blind, parallel-group, delayed start clinical trial in
order to compare the effects of immediate versus delayed treatment with rasagiline in patients with early Parkinson's
disease.
A total of 404 patients were enrolled at 32 sites in the United States and Canada between November 1997 and June 1999.
Participants were older than 35 years and had been confirmed with idiopathic Parkinson's disease.
The patients were randomised to receive rasagiline, 1 mg/day for 1 year, 2 mg/day for 1 year, or matching placebo for 6
months, followed by rasagiline, 2 mg daily, for 6 more months.
The researchers found that the patients who were treated with 2 mg/day of rasagiline had a 2.29-unit smaller increase
in mean, adjusted total UPDRS score compared with those who received placebo for 6 months before rasagiline (P = .05).
Examinations took place at baseline and at 4, 8, 14, 20, 26, 32, 42 and 52 weeks after randomisation. The assessments
included mental, activities of daily living and motor subscales of the Unified Parkinson's Disease Rating Scale (UPDRS)
as well as other scales for activities of daily living.
The 1-year efficacy analysis included the 371 patients who took part in the active treatment phase. There were no
significant differences in baseline characteristics of these participants.
Of the patients receiving 2 mg of rasagiline for the full 12 months, 63.8% were considered responders as were 52.5% of
those who received 1 mg. Of the delayed treatment group, 52.3% were responders. The difference between the delayed
group and the 1 mg group was not considered significant (P = .93).
Rasagiline mesylate, an irreversible monoamine oxidase type B inhibitor, has been shown to improve symptoms of early
Parkinson's, Dr. Siderowf notes. An earlier 6-month placebo-controlled phase of the study had demonstrated better
symptom control among patients taking rasagiline over those taking placebo. In this study, a randomised, delayed-start
design was used to separate an immediate, symptomatic effect from an effect on disease progression.
"Because all subjects were receiving rasagiline in the second phase, the symptomatic effects of the drug were
presumably balanced at the last examination," the researchers explain. Differences observed in performance, therefore,
could not be explained by the symptomatic effects of the drug.
Archives of Neurology 2004;61:561-566. "A controlled, randomized, delayed-start study of rasagiline in early Parkinson
disease"
SOURCE: Doctor's Guide
http://tinyurl.com/26ly7
* * *
Rasagiline May Slow PD Decline
April 20, 2004
A controlled, randomized delayed-start study of rasagiline in early Parkinson disease
Parkinson Study Group
Arch Neurol 2004; 61:561-566
The MAO-B inhibitor rasagiline may delay progression of Parkinson’s disease, according to this study.
Four hundred and four patients with early PD not receiving dopaminergic treatment were randomized to one of three
groups: (1) rasagiline 1 mg/day; (2) rasagiline 2 mg/day; or (3) placebo followed at 6 months by commencement of
rasagiline at 2 mg/day; with the double blind preserved until one year. A report on the six-month interim analysis is
archived at http://www.mdvu.org/emove/article.asp?ID=370
According to the authors, “The randomized delayed-start design used in this study was intended to separate an immediate
symptomatic effect from an effect on disease progression….Because all subjects were receiving rasagiline in the second
phase of the study, the symptomatic effects of the drug were presumably balanced in the last examination.”
Of the 404 patients, 33 withdrew or began dopaminergic treatment before the first assessment in the second six months
of the trial, leaving 371 patients in the intent-to-treat group for efficacy analysis.
A beneficial effect of early vs. delayed rasagiline was seen on total UPDRS and UPDRS activities of daily living, but
not motor scores. After 12 months, compared to Group 3, total UPDRS for Group 1 was better by 1.82 points (p=0.05), and
for Group 2 was better by 2.29 points (p=0.01). The ADL score was 0.96 points better for Group 2 versus Group 1
(p=0.005), but not significantly better for Group 1 versus Group 3. Adverse effects were similar among all groups.
The authors conclude, “Subjects treated with rasagiline, 2 and 1 mg/day, for 12 months showed less functional decline
than subjects whose treatment was delayed for 6 months.” The differences “cannot be fully explained by [rasagiline’s]
symptomatic effect and may be due to a disease-modifying activity of the drug.”
Supported by Teva Pharmaceuticals
SOURCE: We Move
http://tinyurl.com/3g6sg
* * *
----------------------------------------------------------------------
To sign-off Parkinsn send a message to: mailto:[log in to unmask]
In the body of the message put: signoff parkinsn
