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CVT-301 Phase 3 SPAN-PD study met primary endpoint of improvement in
UPDRS III, in data presented at 2017 International Congress of
Parkinson’s Disease and Movement Disorders (MDS)
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Multiple secondary endpoints were supportive of primary endpoint result
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Acorda plans to file New Drug Application (NDA) in U.S. by end of Q2
2017
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Company to host investor webcast to review data from CVT-301 clinical
program on Monday, June 5 at 4:30 pm Eastern / 1:30 pm Pacific
ARDSLEY, N.Y.--(BUSINESS WIRE)--
Acorda Therapeutics, Inc. (Nasdaq:ACOR)
presented data from its Phase 3 SPAN-PD clinical trial of CVT-301
(levodopa inhalation powder) that showed a statistically significant,
clinically meaningful improvement in motor function, as measured by the
Unified Parkinson’s Disease Rating Scale – Part III (UPDRS III) in
people with Parkinson’s experiencing OFF periods. Multiple secondary
endpoints, including achievement of an ON state with maintenance through
60 minutes and Patient Global Impression of Change (PGIC), were
supportive of the primary endpoint result. These findings are being
presented at the International Congress of Parkinson’s Disease and
Movement Disorders (MDS), being held in Vancouver, British Columbia from
June 4-8, 2017.
Acorda is developing CVT-301 as a treatment for symptoms of OFF periods
in people with Parkinson’s taking a carbidopa / levodopa regimen. OFF
periods refer to the re-emergence of Parkinson’s symptoms.
Key Efficacy and Safety Findings: Phase 3 SPAN-PD Study
The poster “Inhaled levodopa (CVT-301, 84-mg dose) significantly
improves motor function during OFF periods in Parkinson’s disease
subjects: A Phase 3 Study (SPAN-PD)” (Poster #LBA34) highlighted
findings from a 12-week, placebo-controlled trial that enrolled 339
participants.
The study met its primary endpoint, with CVT-301 84 mg showing
statistically significant improvement in motor function compared to
placebo as measured by mean change in the UPDRS III at 30-minutes
post-dose at Week 12 (-9.83 vs. -5.91; p = 0.009).
Secondary efficacy analyses were performed using a pre-specified
hierarchy. The order of hierarchy was set based on probability of
success, guided by the Phase 2b results. The primary endpoint (CVT-301
84 mg vs. placebo) was tested first for statistical significance. Upon
achieving significance, the secondary endpoints were tested for CVT-301
84 mg vs. placebo followed by CVT-301 60 mg in the hierarchical order,
as long as each preceding endpoint reached a significance level of P <
0.05. The hierarchical sequence did not reach statistical significance
at Step 3. Unadjusted (nominal) p-values are presented below for all key
secondary endpoints.
Endpoint
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Hierarchy Order
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∆
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P-Value
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84 mg vs. placebo
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Change in UPDRS III at 30 min (primary)
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1
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-3.92
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0.009**
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% OFF to ON and remaining ON at 60 min
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2
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21.60
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0.003**
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Change in UPDRS III at 20 min
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3
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-2.55
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0.062
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% subjects improved on PGIC
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4
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25.00
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<0.001*
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Change in UPDRS III at 10 min
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5
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-2.26
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0.046*
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Change in PD diary OFF time
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6
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0.01
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0.975
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60 mg vs. placebo
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Change in UPDRS III at 30 min
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7
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-3.07
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0.039*
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% OFF to ON and remaining ON at 60 min
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8
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19.50
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0.006*
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Change in UPDRS III at 20 min
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9
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-1.98
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0.147
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% subjects improved on PGIC
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10
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15.20
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0.026*
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Change in UPDRS III at 10 min
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11
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-0.97
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0.387
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Change in PD diary OFF time
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12
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-0.10
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0.722
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** Statistically significant on a nominal and adjusted basis
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* Statistically significant on a nominal basis only
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The most commonly reported adverse events in the CVT-301 84 mg group
compared to the placebo group were: cough (14.9% vs. 1.8%, reported
mostly once/subject), upper respiratory tract infection (6.1% vs. 2.7%),
nausea (5.3% vs. 2.7%), sputum discoloration (5.3% vs. 0%) and
dyskinesia (3.5% vs. 0.0%). When cough was reported, it was typically
characterized as mild. Two of 114 participants receiving CVT-301 84 mg
discontinued the study due to cough.
Key Safety and Exploratory Efficacy Findings: Long-Term Safety Study
In addition to the data presented at the MDS congress, Acorda announced
interim data from an ongoing long-term safety study (CVT-301-005). This
is a 52-week open-label study comparing treatment with CVT-301 84 mg
with an observational control group. Participants were randomized in a
2:1 ratio into either the CVT-301 84 mg arm (n=271) or the observational
control arm (n=127) of the study.
The primary objective of this study is to assess pulmonary function.
Measures include Forced Expiratory Volume in 1 second (FEV1) and
diffusing capacity of the lung for carbon monoxide (DLco).
There were no statistical differences in the mean changes in FEV1 and
DLco from baseline to Week 52 between the CVT-301 84 mg and
observational control groups.
The most common adverse events that were reported in any study arm at
>5% were:
Adverse Event
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Observational Control
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CVT-301 84 mg
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n (%)
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(n=127)
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(n=271)
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Cough
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1 (0.8%)
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35 (12.9%)
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Nasopharyngitis
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6 (4.7%)
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17 (6.3%)
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Dyskinesia
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4 (3.1%)
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15 (5.5%)
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Fall
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3 (2.4%)
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14 (5.2%)
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Bone Fracture (various types)
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3 (2.4%)
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14 (5.2%)
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All reported fractures were judged by the investigators to be unlikely
related or not related to study drug. Most reports of cough were mild
(91%), none was severe. Three of 271 participants (1.1%) receiving
CVT-301 discontinued the study due to cough.
Participants reporting serious adverse events (SAEs) were as follows: 13
(10.2%) in the observational control arm and 40 (14.8%) in the CVT-301
84 mg arm. Urinary tract infection occurred in four participants (1.5%)
receiving CVT-301 84 mg. No other SAEs in the CVT-301 treatment group
were reported at greater than 1%. There was one death in the study, a
drowning in the CVT-301 84 mg group, judged by the investigator to be
not related to study drug.
The study also included several uncontrolled, exploratory efficacy
measurements that were only conducted in the CVT-301 arm of the study.
Exploratory endpoints are hypothesis-generating. Findings included:
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At Week 52, the least-square mean of UPDRS III change from pre-dose at
30 minutes post-dose was -15.13 (n=130).
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85% of participants (n=129) maintained an ON state 60 minutes
post-dose at Week 52.
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73% of participants (n=165) reported improvement as measured by PGIC
at Week 52.
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The least-square mean reduction in daily OFF time among participants
who completed the Week 52 visit (n=108) was 1.15 hours.
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Over the course of the study, the average daily usage of CVT-301 was
2.3 doses per day.
Acorda plans to file an NDA for CVT-301 with the U.S. Food and Drug
Administration (FDA) by the end of the second quarter of 2017, and a
Marketing Authorization Application (MAA) with the European Medicines
Agency (EMA) by the end of the year.
Investor Webcast Information
The Company will host a webcast for investors to provide an overview of
the CVT-301 clinical program on June 5, 2017 at 4:30 pm Eastern / 1:30
pm Pacific. This will include data being presented at the MDS Congress,
as well as additional interim findings from a long-term safety study.
The webcast will include presentations by Matthew Stern, M.D.,
University of Pennsylvania, Peter LeWitt, M.D., Wayne State University
School of Medicine, and Donald Grosset, M.D., Institute of Neurological
Sciences, Queen Elizabeth University Hospital (Glasgow).
The webcast will be available on the Investor
Events page of www.acorda.com
and will be archived in the same location for replay. To participate via
conference call, please dial 800-806-5484 (U.S.) or 416-340-2217
(international) and reference the access code 8170198#. An audio replay
will be available until June 12, 2017 at 1:00 pm Eastern at 800-408-3053
(U.S.) or 905-694-9451 (international) using access code 5949682#.
About Parkinson’s disease and OFF Periods
Approximately one million people in the U.S. and 1.2 million Europeans
are diagnosed with Parkinson’s disease (PD); OFF periods are experienced
by approximately 350,000 in the U.S. and 420,000 in Europe.
Parkinson’s is a progressive neurodegenerative disorder resulting from
the gradual loss of certain neurons responsible for producing dopamine.
It causes a range of symptoms including impaired movement, muscle
stiffness and tremors. As PD progresses, people with Parkinson’s
experience OFF periods, which are characterized by the re-emergence of
PD symptoms. This re-emergence can occur even when an individual’s
treatment regimen has been optimized.
OFF periods can be very disruptive to the lives of people with
Parkinson’s, their families and caregivers. OFF periods can increase in
frequency and severity during the course of the disease.
About CVT-301 (levodopa inhalation powder) and ARCUS®
CVT-301 is a self-administered, inhaled levodopa (L-dopa) therapy in
development for the treatment of symptoms of OFF periods in people with
Parkinson’s disease taking a carbidopa / levodopa regimen.
CVT-301 utilizes Acorda’s investigational ARCUS® platform for
inhaled therapeutics. CVT-301 was designed to deliver a precise dose of
a dry powder formulation of L-dopa to the lung. Oral medication can be
associated with variable onset of action, as the medicine is absorbed
through the gastrointestinal (digestive) tract before reaching the
brain. Inhaled treatments enter the body through the lungs and reach the
brain, bypassing the digestive system.
About Acorda Therapeutics
Founded in 1995, Acorda Therapeutics is a biopharmaceutical company
focused on developing therapies that restore function and improve the
lives of people with neurological disorders. Acorda has a pipeline of
novel neurological therapies addressing a range of disorders, including
Parkinson’s disease and multiple sclerosis. Acorda markets
three FDA-approved therapies, including AMPYRA®
(dalfampridine) Extended Release Tablets, 10 mg. For more information,
please visit the Company’s website at: www.acorda.com.
Forward-Looking Statement
This press release includes forward-looking statements. All statements,
other than statements of historical facts, regarding management's
expectations, beliefs, goals, plans or prospects should be considered
forward-looking. These statements are subject to risks and uncertainties
that could cause actual results to differ materially, including: the
ability to realize the benefits anticipated from the Biotie and Civitas
transactions, among other reasons because acquired development programs
are generally subject to all the risks inherent in the drug development
process and our knowledge of the risks specifically relevant to acquired
programs generally improves over time; the ability to successfully
integrate Biotie’s operations and Civitas’ operations, respectively,
into our operations; we may need to raise additional funds to finance
our expanded operations and may not be able to do so on acceptable
terms; our ability to successfully market and sell Ampyra
(dalfampridine) Extended Release Tablets, 10 mg in the U.S., which will
likely be materially adversely affected by the recently announced court
decision in our litigation against filers of Abbreviated New Drug
Applications (each, an “ANDA”) to market generic versions of Ampyra in
the U.S.; third party payers (including governmental agencies) may not
reimburse for the use of Ampyra or our other products at acceptable
rates or at all and may impose restrictive prior authorization
requirements that limit or block prescriptions; the risk of unfavorable
results from future studies of Ampyra or from our other research and
development programs, including INBRIJA (CVT-301, levodopa inhalation
powder), or any other acquired or in-licensed programs; we may not be
able to complete development of, obtain regulatory approval for, or
successfully market INBRIJA, any other products under development, or
the products that we acquired with the Biotie transaction; the
occurrence of adverse safety events with our products; delays in
obtaining or failure to obtain and maintain regulatory approval of or to
successfully market Fampyra outside of the U.S. and our dependence on
our collaborator Biogen in connection therewith; competition; failure to
protect our intellectual property, to defend against the intellectual
property claims of others or to obtain third party intellectual property
licenses needed for the commercialization of our products; and failure
to comply with regulatory requirements could result in adverse action by
regulatory agencies.
These and other risks are described in greater detail in our filings
with the Securities and Exchange Commission. We may not actually achieve
the goals or plans described in our forward-looking statements, and
investors should not place undue reliance on these statements.
Forward-looking statements made in this press release are made only as
of the date hereof, and we disclaim any intent or obligation to update
any forward-looking statements as a result of developments occurring
after the date of this press release.
View source version on businesswire.com: http://www.businesswire.com/news/home/20170605006069/en/
Source: Acorda Therapeutics, Inc.