Hi all,
If this drug sounds too good to be true, I have some anecdotal experience
you might consider. I was a part of the study until last week; I had a
placebo (worked great!) for the first phase, and then the real drug after
the first six months. It may have slowed progression -- I didn't start
Sinemet until nine years after diagnosis.
A few years ago however we got notice that melanoma had been found in some
trial participants. Although an epidemiologist and a dermatologist rated
the likelihood of a connection as slim, the FDA required skin exams every
three months. Good thing -- last month with no family history of melanoma
or excessive sun (in fact I avoided tanning at all), a biopsy revealed
melanoma (which is why I am no longer in the study).
This is anecdotal, to be sure, but I wonder if the benefits of this drug are
sufficient to out weigh even a tiny increased risk of cancer. It will be
interesting to be sure to see how this issue is 'packaged' in disclosures
for drug marketing. We are accustomed to a world where everything seems
like a potential cause of cancer, and I rated the danger in this instance as
slight (and rasagaline may not be the cause, but no one can say definitely).
But I will say one's perspective changes when a diagnosis is positive.
cb
----- Original Message -----
From: "Murray Charters" <[log in to unmask]>
To: <[log in to unmask]>
Sent: Monday, April 26, 2004 12:34 PM
Subject: PRESS RELEASE: Early Treatment With Rasagiline May Slow Parkinson's
Disease Impairment
> 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
>
> * * *
>
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