--Placebo-Controlled Phase 3 Trial Demonstrated
that ADS-5102 Significantly Reduced Both Dyskinesia and OFF Time at
Six Months in Parkinson’s Disease Patients with Levodopa-induced
Dyskinesia --
Adamas Pharmaceuticals, Inc. (Nasdaq:ADMS) today announced that
results of its Phase 3 EASE LID clinical trial of ADS-5102 were
published online in JAMA Neurology. A New Drug Application
supporting ADS-5102 (amantadine) extended-release capsules for the
treatment of levodopa-induced dyskinesia (LID) in people with
Parkinson's disease is under review by the U.S. Food and Drug
Administration with a Prescription Drug User Fee Act (PDUFA) action
date of August 24, 2017. If approved, ADS-5102 will be the first
and only medicine indicated for the treatment of LID in people with
Parkinson’s disease. The publication can be accessed
at: http://jamanetwork.com/journals/jamaneurology/article-abstract/2630682.
“ADS-5102 reduced the duration, severity, and
impact of dyskinesia in people with Parkinson’s disease. These
statistically significant reductions were maintained for the
entirety of the six-month EASE LID study,” stated Rajesh Pahwa,
M.D., Laverne & Joyce Rider Professor of Neurology, Director of
the Parkinson's Disease and Movement Disorder Center at the
University of Kansas Medical Center. “Also meaningful is that
ADS-5102 significantly reduced OFF time in the study. To my
knowledge, ADS-5102 is the first and only drug with clinically
demonstrated reductions in both dyskinesia and OFF time, conditions
which impact physicians’ ability to treat underlying Parkinson’s
disease in dyskinetic patients.”
“ADS-5102, if approved, will be an important
advancement in the treatment of Parkinson's disease. Many people
with Parkinson’s have levodopa-induced dyskinesias, and these can
be troublesome and impact their quality of life,” said Stanley
Fahn, M.D., H. Houston Merritt Professor of Neurology and Director
Emeritus of the Center for Parkinson’s Disease and Other Movement
Disorders at Columbia University in New York City. “This Phase 3
clinical trial shows that ADS-5102 can significantly reduce these
dyskinesias, thus providing meaningful benefit.”
The randomized, double-blind, placebo-controlled
EASE LID study met its pre-specified primary endpoint demonstrating
that patients who received ADS-5102 experienced a significantly
greater decrease in LID at 12 weeks than those who received placebo
(p=0.0009), as measured by the Unified Dyskinesia Rating Scale
(UDysRS). This improvement was maintained at 24 weeks, with
ADS-5102-treated patients again showing a significantly greater
decrease than placebo-treated patients (p=0.0008). Additionally,
the ADS-5102 group experienced significant improvements in key
pre-specified, hierarchical secondary endpoints compared with the
placebo group, as measured using the Parkinson’s disease home
diary. ADS-5102 treatment resulted in a statistically significant
increase in ON time without troublesome dyskinesia and a
statistically significant decrease in OFF time at 12 and 24 weeks.
Adverse events (AEs) were reported for 89 percent of ADS-5102
patients and 60 percent of placebo patients, and most reported were
mild to moderate. The most common AEs for ADS-5102 versus placebo
were visual hallucinations, peripheral edema, and dizziness. No
study drug-related serious AEs were reported. A total of 17
patients discontinued study treatment due to an AE (13 patients in
the ADS-5102 group vs. four in the placebo group). The EASE LID
trial results were previously presented at the 68th American
Academy of Neurology Annual Meeting and at the 20th International
Congress of Parkinson's Disease and Movement Disorders.
About ADS-5102 and its Clinical
Development Program for Levodopa-induced
DyskinesiaADS-5102 is a high-dose amantadine taken once
daily at bedtime. ADS-5102 was designed to control the initial rate
of rise in plasma concentration to mitigate the risk of central
nervous system adverse events observed shortly after
administration. This dosing regimen results in sustained high
plasma levels of amantadine during morning and throughout waking
hours when dyskinesia occurs, thereby improving the benefit-risk
profile of the drug. If approved, ADS-5102 will meet a significant
unmet need, as the first and only medicine approved for dyskinesia
in people with Parkinson’s disease.
The Phase 3 ADS-5102 levodopa-induced dyskinesia
clinical program was conducted at movement disorder centers across
the United States, Canada and Europe. The program included three
placebo-controlled trials (Phase 2/3 EASED, Phase 3 EASE LID, and
Phase 3 EASE LID 3), and an ongoing, long-term, open-label Phase 3
EASE LID 2 trial. The two placebo-controlled Phase 3 trials met
their primary and all key secondary endpoints, and the pooled data
at 12 weeks demonstrate:
- Primary endpoint: The UDysRS total score was -17.7 in the
ADS-5102 group versus -7.6 in the placebo group (p<0.0001); an
improvement in the UDysRS total score of approximately 30 percent
among those treated with ADS-5102 compared to placebo treated
patients.
- Key secondary endpoints: ON time without troublesome dyskinesia
improved by approximately 40 percent in the ADS-5102 group compared
to placebo (p<0.0001), which represents a 2.4 hour per day
increase in ON time without troublesome dyskinesia, and decreased
OFF time by approximately 45 percent compared to placebo
(p=0.0006), which represents a one hour per day decrease in OFF
time. In totality, patients treated with ADS-5102 in the Phase 3
studies gained approximately four hours of ON time without
troublesome dyskinesia daily.
- Safety and tolerability data: In the Phase 3 EASE LID and EASE
LID 3 trials, the most common adverse events were consistent with
the known amantadine safety profile, and most occurred between
Weeks 2-4 of treatment. The most common adverse reactions (≥5
percent in the active group) were visual hallucinations, dry mouth,
dizziness, peripheral edema, falls, constipation, nausea, anxiety,
decreased appetite, livedo reticularis, insomnia, auditory
hallucinations and orthostatic hypotension. The majority (84
percent) of ADS-5102 treated patients did not discontinue study
drug due to adverse reactions.
The Phase 3 EASE LID 2 long-term, open-label,
safety and efficacy study of ADS-5102 is ongoing. Data were
recently presented at the 21st International Congress of
Parkinson's Disease and Movement Disorders. Results demonstrated
that ADS-5102 was well tolerated and had a treatment effect on
motor complications, as measured by the Movement Disorder
Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Part
IV score, was demonstrated and maintained for up to 88 weeks.
Additionally, patients previously treated with
amantadine immediate-release who switched to open-label ADS-5102
experienced a three point, statistically significant reduction in
MDS-UPDRS Part IV at Week 8 and maintained out to Week 64. These
results were comparable to previous placebo-treated patients, and
patients who have undergone prior deep brain stimulation
treatment.
The safety data are consistent with the
previously reported safety profile of ADS-5102 and the known safety
profile of amantadine.
About Parkinson's Disease and
Levodopa-induced DyskinesiaParkinson's disease is a
chronic neurodegenerative disorder affecting close to 1 million
people in the United States. It is characterized by the progressive
loss of dopaminergic neurons, causing lower levels of endogenous
dopamine and manifesting as symptoms of bradykinesia (slowness of
movement), rigidity, impaired walking, tremor and postural
instability.
Levodopa, which replaces lost dopamine, is the
most effective therapy for all stages of Parkinson's disease and is
considered the "gold standard" therapy. Over time, people require
increasingly higher or more frequent doses of levodopa in order to
avoid the recurrent periods of OFF time when the underlying
symptoms of Parkinson’s disease return. As Parkinson’s disease
progresses, nearly all people on levodopa therapy will also
experience LID, which is characterized by involuntary movements
that are non-rhythmic, purposeless, and unpredictable. Symptoms of
OFF time are characterized by slowness of movement, rigidity,
impaired walking, tremor, and postural instability. These people
often experience multiple fluctuating periods of OFF time and
dyskinesia during any given day, which can impede their movement
and daily function. In the United States, approximately 150,000 to
200,000 people with Parkinson’s suffer from LID.
About Adamas Pharmaceuticals,
Inc.Adamas develops new medicines to improve the daily
lives of those affected by chronic neurologic disorders, including
Parkinson’s disease, multiple sclerosis, epilepsy, and Alzheimer’s
disease. Adamas has pioneered a platform to develop medicines for
chronic neurologic disorders based on an understanding of the
time-dependent biologic processes responsible for disease activity
and drug response. The company’s most advanced product candidate,
ADS-5102, is a high-dose amantadine, taken once daily at bedtime,
in development for levodopa-induced dyskinesia in people with
Parkinson’s disease and for the treatment of walking impairment in
people with multiple sclerosis. A New Drug Application supporting
ADS-5102 for the treatment of levodopa-induced dyskinesia in people
with Parkinson’s disease is under review by the FDA with a PDUFA
date of August 24, 2017. Adamas is exploring other indications for
further development of ADS-5102. Adamas is also investigating
ADS-4101 for the treatment of partial onset seizures in patients
with epilepsy. Additionally, Adamas’ licensed assets, are currently
marketed by Allergan under the brand names NAMENDA XR® and
NAMZARIC®, and Adamas is eligible to receive royalties on sales of
these medicines beginning in June 2018 and May 2020, respectively.
For more information, please visit www.adamaspharma.com.
NAMENDA XR® and NAMZARIC® are trademarks of Merz
Pharma GmbH & Co. KGaA.
Forward-looking Statements
Statements contained in this press release regarding matters that
may occur in the future are "forward-looking statements" within the
meaning of the Private Securities Litigation Reform Act of 1995,
including but not limited to, statements contained in this press
release regarding the potential approval of ADS-5102 for the
treatment of levodopa-induced dyskinesia in people with Parkinson's
disease and the potential clinical benefits of ADS-5102. Because
such statements are subject to risks and uncertainties, actual
results may differ materially from those expressed or implied by
such forward-looking statements. For a description of risks and
uncertainties that could cause actual results to differ from those
expressed in forward-looking statements, including risks relating
to Adamas' research, clinical, development and commercial
activities relating to ADS-5102 and ADS-4101, the regulatory and
competitive environment and Adamas' business in general, see
Adamas' Quarterly Report on Form 10-Q filed with the Securities and
Exchange Commission on May 9, 2017. Investors are cautioned not to
place undue reliance on these forward-looking statements, which
speak only as of the date of this release. Adamas undertakes no
obligation to update any forward-looking statement in this press
release.
Contact:
Martin Forrest
Vice President, Corporate Communications & Investor Relations
Adamas Pharmaceuticals, Inc.
510-450-3528
Ashleigh Barreto
Director, Corporate Communications & Investor Relations
Adamas Pharmaceuticals, Inc.
510-450-3567
ir@adamaspharma.com
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