Promising Data on Cognitive Effects of Safinamide in Early Parkinson's Disease
• Data presented at Movement Disorder Society’s 11th
International Congress
• Management of cognitive impairment in early
Parkinson’s disease patients is a critical unmet medical
need
Geneva, Switzerland, June 8, 2007 – Merck Serono S.A.
(virt-x: SEO) and its partner Newron Pharmaceuticals S.p.a. (SWX:
NWRN) announced today data, which suggest that safinamide, a new
agent in Phase III development for the treatment of
Parkinson’s disease, has an effect on cognitive performance
in study patients with early Parkinson’s disease. These data
were presented yesterday in a poster session at the Movement
Disorder Society’s 11th International Congress in Istanbul,
Turkey.
The data are from a 6-month (24 weeks), randomized, double blind,
placebo-controlled, international Phase III trial. Some results
from this trial were presented last month at the American Academy
of Neurology 59th Annual Meeting and showed that safinamide
significantly improved motor symptoms and activities of daily
living for patients in the trial, as an add-on treatment to
dopamine agonist therapy1. The cognition testing was carried out in
an exploratory manner in selected centers, which agreed to conduct
this part of the trial.
“Parkinson’s disease affects several cognitive
functions even at an early stage of the disease”, said
Professor Anthony Schapira, chairman of the University Department
of Clinical Neuroscience, Royal Free and University College London
Medical School, and an investigator of the study. "These study
results suggest that safinamide may have an effect on cognitive
performance in patients with early Parkinson’s disease, and
has the potential to address a critical unmet medical
need”.
The data demonstrated that the addition of safinamide to a stable
dose of a single dopamine agonist in study patients with early
stage Parkinson’s disease resulted in an improvement in
cognitive domains often impaired in these patients, in particular
executive function (the ability for planning, organizing,
strategizing and paying attention to and remembering details) and
working memory.
Treatment with safinamide at a dose of 50 to 100 mg once daily over
a 24-week period resulted in a statistically significant
improvement in tests assessing executive function, such as the
Strategic Target Detection Test2 (STDT), compared with dopamine
agonist monotherapy. A statistically significant improvement was
also observed in tests for working memory such as Auditory Number
Sequencing3 (ANS). Tests assessing manual dexterity and
attention/vigilance were not statistically different across
treatment groups.
From baseline to the 24th week, cognitive data were available for
41 patients randomized to safinamide 50 to 100 mg once daily, 38 to
safinamide 150 to 200 mg once daily and 44 to placebo. Cognitive
effects were seen as early as 12 weeks after starting safinamide
treatment. The higher safinamide dose range of 150 to 200 mg per
day did not offer any incremental advantage over safinamide 50 to
100 mg per day dose range based on STDT and ANS.
The side effects observed in the safinamide group were similar to
those observed in the placebo group. The most frequent side effects
were gastro-intestinal disorders (nausea, vomiting, abdominal pain
upper).
The cognitive effects of safinamide will be further investigated in
other clinical trials.
Merck Serono has exclusive worldwide rights to develop, manufacture
and commercialize safinamide in Parkinson’s disease,
Alzheimer’s disease, other cognitive disorders and restless
leg syndrome, as per the agreement signed with Newron in October
2006.
1 Phase III data presented at American Academy of Neurology 59th
Annual Meeting in Boston, Massachusetts, USA:
The data are from a trial conducted in Europe, South America and
Asia. A total of 270 early stage Parkinson’s disease patients
(less than 5 years of disease) treated with a stable dose of a
single dopamine agonist for at least 4 weeks were randomized to one
of the three arms of the study to receive either safinamide at a
dose of 50 to 100 mg once daily (90 patients), or safinamide at a
dose of 150 to 200 mg once daily (90 patients) or matching placebo
tablets (90 patients), as an add-on treatment to dopamine agonist
therapy.
Trial data were presented last month at the American Academy of
Neurology 59th Annual Meeting in Boston, Massachusetts, USA.
The data demonstrated that the addition of safinamide to a stable
dose of a single dopamine agonist in study patients with early
stage Parkinson’s disease resulted in a statistically
significant improvement in motor symptoms, as measured by the
Unified Parkinson’s Disease Rating Scale (UPDRS) Part III
Motor Score (primary endpoint). After 24 weeks of treatment with
safinamide at the dose of 50 to 100 mg once daily, the UPDRS Part
III Motor Score was significantly improved over the effect of
dopamine agonist monotherapy (difference between end of study and
baseline of minus 6.0 ± 7.2 in the safinamide-treated group
versus minus 3.6 ± 7.1 in the placebo group; p=0.0419; 95%
CI=[-3.7;-0.1]).
In addition, treatment with safinamide at the dose of 50 to 100 mg
once daily over a 24-week period resulted in a significant
improvement of UPDRS Part II Activities of Daily Living Score,
compared with dopamine agonist monotherapy (difference between end
of study and baseline of minus 2.2 ± 3.8 in the
safinamide-treated group versus minus 1.2 ± 3.5 in the
placebo group; p=0.0248; 95% CI=[-1.8;-0.1]).
The side effects observed in the safinamide group were similar to
those observed in the placebo group.
The higher safinamide dose-range of 150 to 200 mg per day did not
offer any incremental advantage over safinamide 50 to 100 mg per
day dose-range based on UPDRS scoring.
The cognition component of the trial was a secondary endpoint and
was carried out in selected centers, equipped to perform this type
of assessment.
2 Strategic Target Detection Test (complex attention, executive
function): This test requires the subject to touch the target
stimuli (shapes) directly of a touch screen. The participant must
learn which target is correct by choosing one of the stimuli
following computer-generated feedback.
3 Auditory Number Sequencing (attention, working memory, executive
function): Subjects hear a series of numbers (e.g. “9.. 3..
6“; minimum=2 digits, maximum=8 digits) and are asked to
repeat the numbers in order, from lowest to highest, requiring both
working memory maintenance and manipulation.
About safinamide
Safinamide is an alpha-aminoamide derivative which is orally
administered. Safinamide is believed to have a novel mode of action
as a dopamine modulator (comprising both selective and reversible
MAO-B inhibition and also blockade of dopamine reuptake)
complemented by an effect on the glutamate pathway. Studies suggest
that safinamide may combine the inhibition of dopamine re-uptake
and MAO-B, two key mechanisms involved in the control of dopamine
concentration in the brain, and inhibition of glutamate release. If
regulatory approvals are obtained, Merck Serono and Newron believe
that safinamide, as an adjunctive treatment to dopamine agonists
and levodopa, may have a competitive advantage over current
therapies for Parkinson’s disease.
About Parkinson’s disease
Parkinson's disease is a degenerative disorder of the central
nervous system that often impairs the sufferer's motor skills and
speech. Parkinson's disease belongs to a group of conditions called
movement disorders. It is characterized by muscle rigidity, tremor,
a slowing of physical movement (bradykinesia) and, in extreme
cases, a loss of physical movement (akinesia). The primary symptoms
are the results of decreased stimulation of the motor cortex by the
basal ganglia, normally caused by the insufficient formation and
action of dopamine, which is produced in the dopaminergic neurons
of the brain. Secondary symptoms may include high level cognitive
dysfunction and subtle language problems. Parkinson’s disease
is both chronic and progressive.
Forward-looking statements
Some of the statements in this press release are forward looking.
Such statements are inherently subject to known and unknown risks,
uncertainties and other factors that may cause actual results,
performance or achievements of Merck Serono S.A. and affiliates to
be materially different from those expected or anticipated in the
forward-looking statements. Forward-looking statements are based on
Merck Serono’s current expectations and assumptions, which
may be affected by a number of factors, including those discussed
in this press release and more fully described in Serono’s
Annual Report on Form 20-F filed with the U.S. Securities and
Exchange Commission on February 28, 2006. These factors include any
failure or delay in Merck Serono’s ability to develop new
products, any failure to receive anticipated regulatory approvals,
any problems in commercializing current products as a result of
competition or other factors, our ability to obtain reimbursement
coverage for our products, the outcome of any government
investigations and litigation. Merck Serono is providing this
information as of the date of this press release, and has no
responsibility to update the forward-looking statements contained
in this press release to reflect events or circumstances occurring
after the date of this press release.
About Newron Pharmaceuticals
Newron Pharmaceuticals S.p.A. (www.newron.com) is a biopharmaceutical
company focused on novel therapies for diseases of the Central
Nervous System and pain. Newron is undertaking phase III trials
with safinamide, a unique molecule with multiple mechanisms of
action, for the treatment of PD in conjunction with its partner,
Merck Serono S.A., which has the rights to develop the compound in
PD, Alzheimer´s disease, other cognitive disorders and
Restless Legs Syndrome. Recent results of a six-month phase III
trial of safinamide in PD demonstrated its benefit in motor
symptoms and activities of daily living, as well as its improvement
in cognitive function, and good tolerability. Newron and Merck
Serono are planning to expand the development of safinamide to
exploit its potential in Alzheimer´s disease. Phase II trials
with safinamide in Restless Legs Syndrome have shown promising
results. Newron is also conducting phase II trials with ralfinamide
for the treatment of neuropathic pain. The drug has potential
benefit in inflammatory pain, as well. Newron´s clinical
pipeline is supported by a portfolio of early-stage proprietary
compounds generated by its ion channel drug discovery platform.
Newron is headquartered in Bresso, near Milan, Italy. The company
is listed at SWX Swiss Exchange, trading symbol NWRN.
About Merck Serono S.A.
Merck Serono S.A. is a global biotechnology leader, with sales in
over 90 countries. The Company is the world leader in reproductive
health, with Gonal-f®, Luveris® and
Ovidrel®/Ovitrelle®. It has strong market positions in
neurology, with Rebif®, as well as in metabolism and growth,
with Saizen®, Serostim® and Zorbtive™. The Company
has recently entered the psoriasis area with Raptiva®. Merck
Serono's research programs are focused on growing these businesses
and on establishing new therapeutic areas, including oncology and
autoimmune diseases.
Bearer shares of Merck Serono S.A., the holding company, are traded
on the virt-x (SEO).
About Merck
Merck is a global pharmaceutical and chemical company with sales of
EUR 6.3 billion in 2006, a history that began in 1668, and a future
shaped by 35,091 employees in 62 countries. Its success is
characterized by innovations from entrepreneurial employees.
Merck's operating activities come under the umbrella of Merck KGaA,
in which the Merck family holds an approximately 70% interest and
free shareholders own the remaining approximately 30%. In 1917 the
U.S. subsidiary Merck & Co. was expropriated and has been an
independent company ever since.
Posted: June 2007
