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. 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
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 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 any forward-looking statements, except in accordance with
applicable securities laws.
Each of the TSX Venture Exchange and OTCQX has
neither approved nor disapproved the contents of this press
release.
This
announcement is distributed by NASDAQ OMX Corporate Solutions on
behalf of NASDAQ OMX Corporate Solutions clients.
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
HUG#1754160
Citigroup Fdg (AMEX:CTH)
Gráfico Histórico do Ativo
De Mai 2024 até Jun 2024
Citigroup Fdg (AMEX:CTH)
Gráfico Histórico do Ativo
De Jun 2023 até Jun 2024