GENEVA, Switzerland,
November 4, 2010 /PRNewswire/ --
Merck Serono, a division of Merck KGaA, Darmstadt, Germany, and its partner Newron
Pharmaceuticals S.p.A. announced today the top-line results of an
18-month, double-blind, placebo-controlled extension study (study
018) of a previously completed and reported 6-month Phase III study
(study 016) of safinamide. The objective of this extension study
was to assess the long-term (24-month) efficacy and safety of two
doses of safinamide (50 mg and 100 mg once daily tablets) as add-on
therapy to levodopa in patients with advanced Parkinson's disease.
While the primary efficacy endpoint of study 018 measuring
dyskinesia after 24 months of treatment was not met, results of the
exploratory analysis of the pre-specified main secondary endpoint
were consistent with the effect on motor function observed in study
016. Results from the study also further support the safety profile
of safinamide.
The primary efficacy endpoint of study 018 was the mean change
in the ratings of the Dyskinesia Rating Scale1 (DRS). After 24
months, non-statistically significant mean improvements of 0.19 and
0.28 in the DRS score were observed in patients who received
safinamide 50 mg and 100 mg respectively, versus a worsening of
0.32 for the placebo group (respectively p=0.21 and p=0.15 versus
placebo). Dyskinesia, which consists of involuntary and twisting
movements of the face and body, is a major complication of levodopa
therapy, resulting in a significant deterioration of patient
quality of life. At baseline, 32% of patients showed troublesome
dyskinesia.
Out of the 544 patients enrolled in the extension study, 81% of
patients treated with safinamide completed the study (78% in the 50
mg dose group and 83% in the 100 mg dose group) compared to 81% in
the placebo group. The incidences of dropouts, serious adverse
events or clinically notable events among both groups treated with
safinamide were comparable with those in the placebo group over 24
months and similar to the safety profile reported in study 016.
Pre-specified secondary endpoints were analyzed in an
exploratory fashion. The significant effect on "ON" 2 time without
troublesome or minor dyskinesia observed in study 016 (primary
endpoint) was maintained at the end of the 24-month period for both
safinamide doses (1.01 and 1.18 hours for the 50 mg and 100 mg dose
groups respectively versus 0.34 hours for the placebo group;
p=0.0031 and p=0.0002 for the 50 mg and 100 mg dose groups
respectively versus placebo).
"These long-term treatment results are encouraging because they
confirm the safety profile of safinamide and its effect on motor
function observed in the six-month study in this advanced
Parkinson's disease population," said Dr. Bernhard Kirschbaum, Merck Serono's Head of
Global Research and Development. "The effect of safinamide on
dyskinesia will be further explored in an ongoing dedicated pilot
study."
"These results in such a rigorously controlled long-term double
blind study are particularly relevant as they address key questions
in terms of long-term safety and maintenance of the effect on motor
function of safinamide over time," said Luca Benatti, Newron's CEO "These results may
offer new hope to patients with Parkinson's disease as they need to
take medications for long periods of time."
Full study results after completion of ongoing analyses will be
submitted for presentation at upcoming scientific meetings.
The long-term safety data provided by the extension study 018
are part of the clinical development program of safinamide,
together with completed studies 015, 016 and 017, as well as
ongoing MOTION and SETTLE studies. This clinical program is
designed to support an application for marketing authorization of
safinamide as an add-on therapy of dopamine agonist therapy in
patients with early Parkinson's disease and as an add-on of
levodopa therapy in patients with advanced Parkinson's disease.
Merck Serono has exclusive worldwide rights to develop,
manufacture and commercialize safinamide in Parkinson's disease,
Alzheimer's disease and other therapeutic applications, as per the
agreement signed with Newron in 2006.
Footnotes
1 The Dyskinesia Rating Scale is designed: 1) to assess the
severity of overall dyskinesia, based on interference with
activities of daily living; 2) to distinguish chorea from dystonia,
the two major types of dyskinesia in PD; and 3) to identify the
single most disabling form of dyskinesia.
Dyskinesia is a major complication of levodopa therapy
experienced by patients with Parkinson's disease and it consists of
involuntary, unwanted and twisting movements of the face, body and
limbs.
2 The times in which the levodopa is effective and the person
with Parkinson's disease is able to function normally is called
"ON" time.
Study 018 design
The objective of this extension study was to evaluate the
long-term efficacy and safety of a 50 mg and 100 mg/day dose of
safinamide, compared with placebo, as add-on treatment to levodopa
therapy in patients with mid- to late-stage Parkinson's disease
experiencing motor fluctuations.
This Phase III study was a double-blind, randomized,
placebo-controlled, 18-month extension study. Patients who
completed the double-blind treatment period in Study 016 were
eligible to enter the extension study and continued to take the
same treatment originally administered in Study 016 (50 mg/day, 100
mg/day or placebo), along with the same dose of levodopa. It
enrolled 544 patients from study 016 with mid- to late-stage
idiopathic Parkinson's disease (more than 3 years of disease
duration) receiving stable doses of levodopa, who had motor
fluctuations with >1.5 hours of "OFF" time during the day.
Patients who entered the initial 6-month Phase III trial (study
016) were given the opportunity to continue the study for an
additional 18 months, receive other treatments for Parkinson's
disease, or to discontinue therapy. Of the 669 patients originally
enrolled in Study 016, 544 entered the 18-month extension; 440
completed the 18-month extension period.
About safinamide
Safinamide is an alpha-aminoamide that is currently being
developed by Merck Serono and Newron as an add-on therapy to
dopamine agonists or levodopa in patients with early or late-stage
Parkinson's disease. It is believed to have both dopaminergic and
non-dopaminergic activities, including selective and reversible
inhibition of monoamine oxidase B (MAO-B), activity-dependent
sodium channel antagonism and inhibition of glutamate release in
vitro. Studies are ongoing to better understand safinamide's
actions in patients with Parkinson's disease.
About Parkinson's disease
Parkinson's disease is a degenerative disorder of the central
nervous system that often impairs the patient'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. It is estimated that more than 3
million people in the industrialized countries suffer from
Parkinson's disease.
About Merck Serono
Merck Serono is the division for innovative prescription
pharmaceuticals of Merck KGaA, Darmstadt, Germany, a global pharmaceutical and chemical
company. Headquartered in Geneva,
Switzerland, Merck Serono discovers, develops, manufactures
and markets innovative small molecules and biopharmaceuticals to
help patients with unmet medical needs. In the United States and Canada, EMD Serono operates through separately
incorporated affiliates.
Merck Serono has leading brands serving patients with cancer
(Erbitux(R), cetuximab), multiple sclerosis (Rebif(R), interferon
beta-1a), infertility (Gonal-f(R), follitropin alfa), endocrine and
metabolic disorders (Saizen(R) and Serostim(R), somatropin),
(Kuvan(R), sapropterin dihydrochloride) as well as cardiometabolic
diseases (Glucophage(R), metformin), (Concor(R), bisoprolol),
(Euthyrox(R), levothyroxine). Not all products are available in all
markets.
With an annual R&D expenditure of more than EUR 1 billion, Merck Serono is committed to
growing its business in specialist-focused therapeutic areas
including neurodegenerative diseases, oncology, fertility and
endocrinology, as well as new areas potentially arising out of
research and development in autoimmune and inflammatory
diseases.
About Merck
Merck is a global pharmaceutical and chemical company with total
revenues of EUR 7.7 billion in 2009,
a history that began in 1668, and a future shaped by approximately
40,000 (including Merck Millipore) employees in 64 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.
For more information, please visit http://www.merckserono.com or
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