PRESS RELEASE
March 28, 2014
Cynapsus Announces Interim
Summary Results of Human Healthy Volunteer Single 25mg Study for
APL-130277
Results Support Higher Drug
Concentration in the Blood as a Result of Higher Dose
Strip
TORONTO, CANADA - Cynapsus Therapeutics Inc. (CTH:
TSX-V) (CYNAF: OTCQX), a specialty pharmaceutical company, today
announced positive interim data from its recently completed healthy
volunteer pilot study of a single 25mg sublingual strip
(APL-130277) dose of apomorphine. APL-130277 is an
easy-to-administer, fast-acting reformulation of apomorphine, which
is the only approved drug (in the United States, Europe, Japan and
other countries) to rescue patients from "off" episodes. The
interim CTH-104 study results indicate that a higher load of drug
on the strip does result in a higher amount of drug entering the
blood stream.
Mr. Anthony Giovinazzo, President and CEO of
Cynapsus commented, "Results from the first group of subjects of
the CTH-104 clinical study are an important de-risking event for
our product and set the stage for identifying efficacious doses for
our upcoming clinical studies in 2014. We are encouraged that the
25mg strip was safe and well tolerated. Further, a significantly
higher amount of drug accumulated in the blood stream as compared
to the 10mg and 15mg strips that were tested in our CTH-103 study.
This interim data shows that the APL-130277
strip can provide a concentration of apomorphine in the
blood associated with an expected minimum efficacious concentration
(i.e. approximately 3ng/ml) for over 2 hours, therefore potentially
providing a significant reversal of the "off" state for patients
with Parkinson's disease."
Dr. Albert Agro, Chief Medical Officer at
Cynapsus, also commented: "The early PK and safety data from
CTH-104 confirms that our formulation has both the potential for
clinical efficacy and safety advantages over the sub-cutaneous
injection of apomorphine. We look forward to the initiation of
the upcoming clinical program assessing the effectiveness of
APL-130277 in patients with Parkinson's disease."
CTH-104 Clinical Trial
Design and Results
Background
As reported on January 13, 2104, the third cohort
of the CTH-103 study was designed to compare the 25mg sublingual
thin film strip (APL-130277) to the 4mg subcutaneous injection.
This third cohort could not be dosed due to the dose-limiting
adverse events experienced with the 3mg subcutaneous
injection. The 15mg sublingual strip (APL-130277), which was
the corresponding dose to the 3mg subcutaneous injection, resulted
in side effects that were mild-to-moderate and not dose
limiting.
The current CTH-104 study is a single dose, single
arm, placebo-controlled, healthy volunteer pharmacokinetic study,
which is designed to examine the pharmacokinetic profile of the
25mg dose of APL-130277.
The study is designed to include 16 healthy human
volunteers (two placebo and 14 active). Nine (9) of the sixteen
(16) subjects were completed in the first group, reported herein.
The remaining subjects will be dosed and analysed within the next
15-30 days, at which point the combined data will be released.
Key Findings
-
Comparing the increased dose of the 25mg
(APL-130277) strip used in CTH-104 to that of the 15mg strip
previously used in CTH-103, indicates that a higher concentration
of apomorphine was achieved. In this first group of subjects,
sublingual delivery of the higher 25mg strip dose resulted in more
adverse events with a greater severity than seen with the 15
mg dose. The side effects were mild to moderate and were not
defined to be dose limiting.
About
Apomorphine
Apomorphine, a potent dopamine agonist, is the
only drug approved specifically for the treatment of acute motor
fluctuations/hypomobility (freezing or "off" episodes) in patients
with advanced Parkinson's disease. Presently, apomorphine is
administered by intermittent subcutaneous injection usually via a
pre-filled injection pen, or, in some cases outside the United
States, by continuous infusion pump. Drawbacks associated with
subcutaneous injection therapy for patients and caregivers include
aversion to needles, the need for multiple injections, which can be
painful and are often associated with irritation and inflammation
at the injection site, and the requirement for a degree of manual
dexterity that some Parkinson's patients find difficult.
Critical Next
Steps
For development of APL-130277 in the United
States, the Corporation will follow the 505(b)(2) regulatory
pathway. Specifically, the Corporation is pursuing the
reformulation of apomorphine from a subcutaneous injection to a
convenient and more tolerable and safe sublingual thin film strip.
The drug being delivered (apomorphine) is identical to the drug
used in the injection, and its use will be intended as an acute
rescue therapy for Parkinson's patients experiencing acute,
intermittent hypomobility (i.e. "off" episodes) associated with
advanced Parkinson's disease, which is the description of the use
of apomorphine in the current US approved label.
The 505(b)(2) pathway will require that the
Corporation provide statistically sufficient clinical evidence that
Parkinson's patients experience management of their "off" episodes,
as a result of delivery of apomorphine via the sublingual thin film
strip route. The primary end point will be based on changes in the
Unified Parkinson's Disease Rating Scale Part III (UPDRS III)
movement score. In addition, the Corporation will be required
to provide in a separate study, statistically sufficient clinical
evidence that administering apomorphine via a sublingual thin film
route results in Parkinson's patients experiencing low to no oral
irritation as a result of multiple daily exposures to the drug for
an extended period.
To achieve this, the Corporation currently expects
to complete the following clinical studies:
-
CTH-105 Pilot
Study. A pilot study in patients with Parkinson's
disease who are naïve to the use of apomorphine and who experience
at least one daily "off" episode with a total duration of "off" in
any 24-hour period of at least 2 hours. This study is
planned to examine the effect of APL-130277 on relieving "off"
episodes over a single day with a dose-titration used to determine
dose strengths necessary for future clinical development. The
CTH-105 study is expected to begin in mid-2014 subsequent to the
acceptance of an Investigational New Drug (IND) application by the
FDA. CTH-105 is expected to be completed by the end of Q3
2014.
-
CTH-200 Bridging
Study. A single dose, crossover comparative
bioavailability and PK study in healthy volunteers. This study is
designed to provide the clinical "bridge" to the FDA's finding of
safety and efficacy for the Reference Listed Drug (s.c.
Apomorphine). The CTH-200 Bridging Study is expected to begin in
mid-2014 subsequent to completion of CTH-105. It is
expected to be complete by end of Q3 2014 and is required under the
FDA's 505(b)(2) regulations to demonstrate comparability to the
reference listed drug.
-
CTH-300a Efficacy Study in
apomorphine naïve patients. A double-blind,
placebo-controlled, parallel-design study with Parkinson's patients
who have at least one "off" episode every 24 hours, with total
"off" time of at least 2 hours. The primary end point will be the
change in the UPDRS III score.
-
CTH-300b Efficacy Study in
apomorphine experienced patients. A double blind,
placebo controlled, crossover-designed study with Parkinson's
patients who are presently controlled with the use of apomorphine.
The primary end point will be the change in the UPDRS III
score. Upon successful completion of CTH-300a and CTH-300b,
the Corporation will provide the results to the FDA and request a
meeting to seek final guidance for the design of Safety Study
(CTH-301).
-
CTH-301 Safety
Study. A long-term safety study in apomorphine naïve
Parkinson's patients who have at least one "off" episode every 24
hours, with total "off" time of at least 2 hours. The Safety Study
is expected to start in early 2015 and be completed by the end of
2015. The study will specifically look at the safety and
tolerability of the new delivery route over a minimum period of 16
weeks.
The above clinical development plan has been
vetted with both clinical experts and regulatory consultants who
have expertise in overseeing FDA 505(b)(2) submissions to the
Agency.
In parallel to the studies described above, the
Corporation will be performing the necessary scale-up, process
validation and stability as part of the Chemistry, Manufacturing
and Controls ("CMC") requirements for the filing of the NDA.
Accordingly, all development will be performed according to current
Good Manufacturing Practices ("cGMP") methodology.
Upon completion of the efficacy and safety
studies, as well as the CMC section, the Corporation expects will
begin preparation of a FDA 505(b)(2) NDA in 2016.
About Cynapsus
Therapeutics
Cynapsus is a specialty pharmaceutical company
developing a convenient and easy to use sublingual (oral) thin film
strip for the acute rescue of "off" motor symptoms of Parkinson's
disease. Cynapsus' drug candidate, APL-130277, is an
easy-to-administer, fast-acting reformulation of apomorphine, which
is the only approved drug (in the United States, Europe, Japan and
other countries) to rescue patients from "off" episodes. Cynapsus
is focused on maximizing the value of APL-130277 by completing
pivotal studies in advance of a New Drug Application ("NDA")
expected to be submitted in 2016.
Over one million people in the U.S. and an
estimated 4 to 6 million people globally 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. Based on
a recent study and the results of the Company's Global 500
Neurologists Survey, it is estimated that between 25 percent and 50
percent of patients experience "OFF" episodes in which they have
impaired movement or speaking capabilities. Current medications
only control the disease's symptoms, and most drugs become less
effective over time as the disease progresses.
More information about Cynapsus (TSX-V: CTH)
(OTCQX: CYNAF) is available at www.cynapsus.ca and at the System
for Electronic Document Analysis and Retrieval (SEDAR) at
www.sedar.com.
Contact
Information
Cynapsus Therapeutics
Anthony Giovinazzo
President and CEO
(416) 703-2449 x225
ajg@cynapsus.ca
Andrew Williams
COO & CFO
(416) 703-2449 x253
awilliams@cynapsus.ca
Michael Rice
LifeSci Advisors, LLC
1350 Avenue of the Americas, Suite 2801
New York, NY 10019
646-597-6979
Forward Looking
Statements
This announcement contains "forward-looking
statements" within the meaning of applicable securities laws.
Generally, these forward-looking statements can be identified by
the use of forward-looking terminology such as "plans", "expects"
or "does not expect", "is expected", "budget", "scheduled",
"estimates", "forecasts", "intends", "anticipates" or "does not
anticipate", or "believes" or variations of such words and phrases
or state that certain actions, events or results "may", "could",
"would", "might" or "will be taken", "occur" or "be achieved".
Forward-looking statements are subject to known and unknown risks,
uncertainties and other factors that may cause the actual results,
level of activity, performance or achievements of Cynapsus to be
materially different from those expressed or implied by such
forward-looking statements, including but not limited to those
risks and uncertainties relating to Cynapsus' business disclosed
under the heading "Risk Factors" in its latest Annual Information
Form and its other filings with the various Canadian securities
regulators which are available online at www.sedar.com. Although
Cynapsus has attempted to identify important factors that could
cause actual results to differ materially from those contained in
forward-looking statements, there may be other factors that cause
results not to be as anticipated, estimated or intended. There can
be no assurance that such statements will prove to be accurate, as
actual results and future events could differ materially from those
anticipated in such statements. Accordingly, readers should not
place undue reliance on forward-looking statements. Cynapsus does
not undertake to update any forward-looking statements, except in
accordance with applicable securities laws.
Neither of the TSX Venture Exchange or OTCQX has
approved or disapproved the contents of this press release.
--30--
This
announcement is distributed by NASDAQ OMX Corporate Solutions on
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The issuer of this announcement warrants that they are solely
responsible for the content, accuracy and originality of the
information contained therein.
Source: Cynapsus Therapeutics Inc. via Globenewswire
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