TORONTO, Dec. 8, 2015
(GLOBE NEWSWIRE) -- Cynapsus Therapeutics Inc. ("Cynapsus")
(NASDAQ:CYNA) (TSX:CTH), a specialty central nervous system ("CNS")
pharmaceutical company developing and preparing to commercialize an
easy-to-use, sublingual thin film for the on-demand management of
debilitating OFF episodes associated with Parkinson's disease
("PD"), today announced the presentation of updated clinical data
from the Phase 2 trial of APL-130277 in five poster presentations
at the XXI World Congress on Parkinson's Disease and Related
Disorders ("IAPRD") Meeting in Milan, Italy. These results showed
APL-130277 significantly improved PD symptoms (as measured by
MDS-UPDRS Part III), rapidly turning patients from the OFF to ON
state and was generally safe and well-tolerated.
"These additional Phase 2 data presented at the World Congress
further support the potential of APL-130277 to rapidly
convert patients with motor fluctuations from a debilitating
OFF state to ON," said Dr. Albert Agro, Chief Medical Officer
of Cynapsus. "We are encouraged by the clinical profile
demonstrated to-date and the possibility to offer a treatment
alternative for patients who suffer with Parkinson's
disease. We continue to enroll patients in our pivotal Phase 3
efficacy and safety studies, and expect to share top-line data in
mid-to-late 2016. We also expect to file our New Drug
Application for APL-130277 with the U.S. FDA near the end of
2016."
Cynapsus will also host a symposium at the World Congress and is a
platinum sponsor. Additional information can be found at the Web
site link: http://www.oic.it/iaprd2015/
Phase 2 Clinical Study
Design
In the CTH-105 multicenter open-label study, APL-130277 was
assessed in 19 patients with PD who experienced the debilitating
effects of OFF episodes, with a total duration of OFF of at least
two hours daily. By withholding the first dose of levodopa in the
morning, patients were dosed in the practically defined OFF state,
one of the most difficult to convert to an ON state. Patients were
then given escalating doses of APL-130277 until ON was achieved, as
documented by study staff and the patient. The MDS-UPDRS Part III
score was measured as a secondary endpoint at 15, 30, 45, 60 and 90
minutes after APL-130277 administration.
Poster Presentations
Poster #1: Phase 2 Efficacy
Data
The CTH-105 study included PD patients with at least one OFF
episode per day and two or more hours of daily OFF
time. Patients were dosed in the morning OFF state, starting
with APL-130277 10 mg and increased in 5 mg increments until a full
ON was achieved, to a maximum of 30 mg. MDS-UPDRS Part III and ON
and OFF status was determined pre-dose and 15, 30, 45, 60 and 90
minutes after dosing.
Data presented today at IAPRD showed that 15 of 19 patients dosed
achieved a satisfactory full ON following APL-130277
administration. Of the 15 responders, all turned fully ON within 30
minutes of dosing and six within 15 minutes. Thirteen of 15
remained fully ON for at least 30 minutes and 9 of 15 for at least
60 minutes. Mean MDS-UPDRS Part III change from pre-dose to 15, 30,
45, 60 and 90 minutes after dosing for all 19 patients was -11.5,
-14.6, -15.0, -13.5 and -9.2, respectively.
This study demonstrated that APL-130277 rapidly converted PD
patients from the OFF to the full ON state and provided clinically
meaningful improvement in MDS-UPDRS Part III scores. In addition,
much of the benefit was sustained through 90 minutes.
Poster #2: Phase 2 Safety
Data
The safety data from CTH-105 assessed 19 subjects who received a
total of 77 doses of APL-130277, with doses ranging from 10 mg to
30 mg. Subjects were pre-medicated for three days with
trimethobenzamide, which was continued during the study.
Data showed that in this study, 13 (68.4%) patients experienced an
adverse event "AE", with most experiencing mild AEs. The most
common AEs were dizziness (7/19, 36.8%), somnolence (6/19, 31.6%),
nausea (4/19, 21.1%) and yawning (3/19, 15.8%). There was one
serious AE of dysphagia deemed not related to APL-130277 by the
investigator. There were no AEs of local oral irritation and no
subjects discontinued due to AEs.
These results showed that APL-130277 was safe and well-tolerated in
PD patients with OFF episodes. The most common AEs were mild to
moderate, and are commonly associated with dopaminergic
medications.
Poster #3: Phase 2 Subgroup
Analysis
This CTH-105 subgroup analysis showed that when evaluating patients
by number OFF episodes, age, levodopa dose, number of classes of PD
medications and years of OFF episodes, the percentage of patients
turning ON with APL-130277, absolute MDS-UPDRS improvement and
percent MDS-UPDRS improvement were similar between
groups.
Results also showed that APL-130277 rapidly converted 15 of the 19
PD patients dosed from the OFF to the full ON state regardless of
disease severity.
Poster #4: Phase 2 Dose
Analysis
Results of CTH-105 showed that of the 19 patients dosed, 15
converted from OFF to ON with APL-130277. There was no
correlation with baseline levodopa dose, number of daily OFF
episodes or number of PD medications and effective dose of
APL-130277. In addition, baseline disease severity did not predict
the effective doses needed to turn an OFF patient ON. Therefore,
all patients should be titrated starting with the lowest possible
dose.
Poster #5: Phase 2 MDS-UPDRS
Analysis
In CTH-105, the MDS-UPDRS Part III and ON and OFF status was
determined pre-dose and 15, 30, 45, 60 and 90 minutes after
dosing. This poster showed that of the 19 patients dosed, 15
converted from OFF to full ON with APL-130277. Of nine patients who
were ON at 30 minutes but OFF at 15 minutes, the mean MDS-UPDRS
Part III absolute and percentage change was -18.0 and -41.4%,
respectively, when ON and -10.1 and -24.6%, respectively, when
OFF. Of six patients who turned fully ON at 15 minutes, the
mean MDS-UPDRS Part III absolute and percentage change was -14.5
and 38.9% at ON, respectively.
These results showed that APL-130277 rapidly converts PD patients
from the OFF state to the ON state. An MDS-UPDRS Part III
improvement of over 10 points and 25% change is needed to turn a
patient from the morning OFF state to a full ON state.
Cynapsus Sponsored
Symposium
The Importance and Impact of OFF Episodes in
PD Patients and the Need for Turning ON
Therapies
Today's symposium on December 8, 2015, will include discussions on
motor complications in PD, current therapies for motor
complications and rescue therapies. It will conclude with a
key opinion leader panel discussion. It is being held from
12:00 to 13:30 CET in the Silver Hall.
About Parkinson's Disease and OFF
Episodes
More than one million people in the U.S. and an estimated four to
six million people worldwide suffer from Parkinson's disease.
Parkinson's disease is a chronic and progressive neurodegenerative
disease that impacts motor activity, and its prevalence is
increasing with the aging of the population. OFF episodes are a
complication of Parkinson's disease that leave patients rigid and
unable to move and communicate. An estimated one quarter to one
half of all people with Parkinson's disease whose symptoms are
otherwise managed with ongoing drug therapy experience OFF episodes
at least once daily and up to six times daily, with each episode
lasting between 30 and 120 minutes.
OFF and motor symptoms of Parkinson's disease are measured by
MDS-UPDRS Part III. The MDS-UPDRS Part III is used by neurologists
to measure the severity of Parkinson's disease.
About Cynapsus
Cynapsus is a specialty Central Nervous System pharmaceutical
company developing and preparing to commercialize an easy-to-use,
sublingual thin film for the on-demand management of debilitating
OFF episodes associated with Parkinson's disease (PD). The Company
recently completed a Phase 2 clinical trial for its product
candidate, APL-130277, a sublingual formulation of apomorphine
hydrochloride, or apomorphine. Apomorphine is the only molecule
approved for acute, intermittent treatment of OFF episodes for
advanced PD patients, but is currently only approved as a
subcutaneous injection in the United States. APL-130277 is a
"turning ON" medication designed to rapidly, safely and reliably
convert a PD patient from the OFF to the ON state while avoiding
many of the issues associated with subcutaneous delivery of
apomorphine. It is designed to convert all types of OFF episodes,
including morning OFF episodes, often considered the most difficult
to treat. Cynapsus has initiated its Phase 3 clinical program for
APL-130277, relying on the abbreviated Section 505(b)(2) regulatory
pathway in the United States, and the Company intends to submit a
new drug application ("NDA") in 2016.
Forward-Looking Statements
This announcement contains "forward-looking statements" within the
meaning of applicable securities laws, including without
limitation, the expected sharing of top-line data for Phase 3
efficacy and safety studies in mid to late 2016, and the expected
NDA submission of APL-130277 in 2016. These forward-looking
statements include information about possible or assumed future
results of the Company's business, financial condition, results of
operations, liquidity, plans and objectives. In some cases, you can
identify forward-looking statements by terminology such as
"believe," "may," "estimate," "continue," "anticipate," "intend,"
"should," "plan," "expect," "predict," "potential," or the negative
of these terms or other similar expressions. These forward-looking
statements are based on the Company's current expectations and
beliefs and inherently involve significant risks and uncertainties.
Actual results and the timing of events could differ from those
anticipated in such forward-looking statements as a result of risks
and uncertainties, and include, but are not limited to, those
factors identified under the caption "Risk Factors" in the
Company's Form 10-Q filed with the United States Securities and
Exchange Commission (the "SEC") on November 12, 2015 and its other
filings and reports in the United States with the SEC available on
the SEC's web site at www.sec.gov, and in Canada with the various
Canadian securities regulators, which are available online at
www.sedar.com. Furthermore, unless otherwise stated, the
forward-looking statements contained in this press release are made
as of the date of this press release, and the Company has no
intention and undertakes no obligation to update or revise any
forward-looking statements, whether as a result of new information,
future events, changes or otherwise, except as required by
law.
Neither the NASDAQ nor the TSX has approved or disapproved of the
contents of this press release.
CONTACT: Company Contact:
Kristen Galfetti
Vice President, Investor Relations
(416) 703-2499 x246
kgalfetti@cynapsus.ca
Media Contact:
Russo Partners LLC
Matt Middleman
(212) 845-4272
matt.middleman@russopartnersllc.com
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