Results Support Expected 505(b)2 Path to New Drug Application (NDA) in the United States
TORONTO, CANADA, Jan 13, 2014 (Marketwired via COMTEX) -- Cynapsus Therapeutics Inc. CA:CTH +3.49% (otcqx:CYNAF), 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(R) or Apo-Go(R)) 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(R), 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(R) 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.
-- 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
-- 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.
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(R) NDA (total of 62 patients), including studies in apomorphine-naive and in apomorphine-experienced Parkinson's patients, plus a safety study in apomorphine-naive 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.
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 CA:CTH +3.49% (otcqx:CYNAF) is available at www.cynapsus.ca and at the System for Electronic Document Analysis and Retrieval (SEDAR) at www.sedar.com .
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.
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