Cynapsus Therapeutics Inc. : Cynapsus Announces Completion of Human Healthy Volunteer Crossover Study Results for APL-130277
January 13, 2014
Results Support Expected 505(b)2 Path to New Drug Application (NDA) in the
United States
TORONTO, CANADA - Cynapsus Therapeutics Inc. (CTH: TSX-V) (CYNAF: OTCQX), a
specialty pharmaceutical company, today announced positive top line data from
its recently completed healthy volunteer pilot crossover trial comparing APL-
130277, a sublingual thin film strip formulation of apomorphine, to a
commercially available injectable formulation of apomorphine. The study results
further support the advancement of APL-130277 for management of "OFF" episodes
in Parkinson's disease through the section 505(b)(2) regulations of the United
States Food and Drug Administration Act, which provides an accelerated path to
approval for new formulations of approved medicines.
Mr. Anthony Giovinazzo, President and CEO of Cynapsus commented, "Results from
this CTH103 clinical study are an important de-risking event for our product and
set the stage for completing in the next two years the clinical requirements for
qualifying APL-130277 for a 505(b)(2) New Drug Application. Importantly, the
data indicate that APL-130277 may have advantages over an injectable product
(i.e. apomorphine hydrochloride subcutaneous injection, Apokyn® or Apo-Go®) by
reducing the frequency and intensity of side effects including nausea and
vomiting versus those commonly reported for a subcutaneous injectable
formulation. The results also suggest that APL-130277 exhibits comparable time
to maximal concentrations in the blood and therapeutic plasma levels that are
similar or longer than those seen following subcutaneous injection."
Mr. Giovinazzo added, "Assuming concurrence with the regulatory authorities, we
expect that results of this study will enable us to proceed directly to the
completion of two small efficacy studies and a safety study, in patients with
Parkinson's disease. Our plan is to design a clinical registration program for
APL-130277 that demonstrates efficacy as measured by both time to "ON" and
duration of "ON" in patients with Parkinson's disease, with possible
advantageous adverse event claims. If substantiated in the registration
clinical trials, the findings from the CTH103 healthy volunteer study indicate
that the sublingual formulation of APL-130277 could have measurable advantages
for patients and their caregivers over a subcutaneous injection of apomorphine."
Dr. Albert Agro, Chief Medical Officer at Cynapsus, also commented: "We are
indebted to The Michael J. Fox Foundation for Parkinson's Research for
supporting this important milestone for APL-130277. Their support was
fundamental to the success of this study. We are very pleased with the results,
which confirm that our sublingual thin film strip formulation is effective at
delivering apomorphine with the potential to reach efficacious plasma levels,
but with what appears to be a reduced side effect profile compared to the
subcutaneous injectable formulation. We look forward to initiating the efficacy
program in patients suffering from Parkinson's disease with debilitating motor
complications."
CTH103 Clinical Trial Design and Results
The CTH103 study was a three-dose active comparator, placebo-controlled,
randomized cross-over trial to examine the pharmacokinetic profile of sublingual
administered APL-130277 compared to the subcutaneous injection of apomorphine in
healthy volunteers. The study was completed outside the United States with the
active comparator Apo-go®, the approved subcutaneous injection in Europe and
Asia.
The 10mg and 15mg APL-130277 sublingual thin film strips were crossed over to
2mg and 3mg subcutaneous injections, with N=15 and N=14 for the two cohorts,
respectively. The Tmax (time to maximum concentration) was 31 minutes and 40
minutes for the two doses of APL-130277. The rapid uptake of apomorphine is
similar to that described in the Apokyn® label (i.e. between 10 and 60 minutes).
In addition, the sublingual thin film strip delivery system achieved an average
minimum threshold exposure of approximately 3 ng/ml in plasma for both dose
levels administered, which is expected to be sufficient to restore motor control
(the "ON") in patients requiring the lowest titratable doses of a subcutaneous
injection. Â The sublingual thin film strips also demonstrated proportionality
between the doses. The results from CTH103 support the pursuit of an efficacy
program under the 505(b)(2) regulatory path.
The intent in the CTH103 study for the third cohort was to compare the 25mg
sublingual thin film strip (APL-130277) to the 4mg subcutaneous injection, but
this third cohort could not be dosed due to the dose-limiting adverse events
experienced with the 3mg subcutaneous injection. The 15mg APL-130277 side
effects were mild-to-moderate and not dose limiting. The Company is in the
process of preparing a single arm, healthy volunteer pharmacokinetic study to
look at the 25mg APL-130277 sublingual strip (without a crossover to the
injection), which is expected to be completed in Q1 2014.
Key Findings
·        Sublingual delivery of apomorphine with APL-130277 was better
tolerated than the subcutaneous injection in the studied doses;
·        The PK profile of APL-130277 was proportional between doses and
exposures above the minimum expected efficacious level were similar to or longer
than seen following subcutaneous injection;
·        APL-130277 achieved apomorphine mean Tmax of 31 and 40 minutes for the
10mg and 15mg formulations, respectively. The subcutaneous injection achieved
apomorphine Tmax of27 and 24 minutes for the 2mg and 3mg formulations,
respectively;
·        The mean time to reaching a plasma concentration of apomorphine
associated with therapeutic benefit of "Time to ON" was 10-13 minutes for the
two doses of APL-130277 versus 4-5 minutes for the subcutaneous injection. The
times achieved are reflective of patients' expectations for a rapid return to
"ON"; and
·        APL-130277 was safe and well-tolerated in CTH103 as in previous
clinical studies (i.e. CTH101 and CTH102). There were fewer adverse events and
the adverse events were less intense for subjects exposed to the 10mg and 15mg
strips versus the subcutaneous 2mg and 3mg injections. The adverse events for
the 3mg injection dose were dose-limiting and escalation of the subcutaneous
injection to a higher dose as a comparator could not be pursued.
Next Steps
Cynapsus believes that results of the CTH103 study justify requesting a meeting
with the US FDA to confirm the Company's plan to demonstrate efficacy and safety
benefits in a limited number of small clinical studies of APL-130277.
 Specifically, the Company seeks to conduct small efficacy studies in "OFF"
episode management, similar to those completed as part of the Apokyn® NDA (total
of 62 patients), including studies in apomorphine-naïve and in apomorphine-
experienced Parkinson's patients, plus a safety study in apomorphine-naïve
Parkinson's patients. Cynapsus currently expects the initial efficacy studies to
be completed by the end of 2014 and a safety study to be completed by the end of
2015, with a 505(b)(2) NDA filing possible in the first half of 2016.
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 US, 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.
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. Cynapsus anticipates a trade sale or
out-licensing to an appropriate global pharmaceutical partner before such an
application is submitted.
Over one million people in the U.S. and an estimated 4 to 6 million people
globally suffer from Parkinson's disease (National Parkinson Foundation, 2014).
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
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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 Annual Information Form filed
on August 30, 2013 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
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