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Cynapsus Therapeutics Inc. : Cynapsus Announces Positive Results of CTH-104 Clinical Study of APL-130277 for Parkinson's Disease
April 24, 2014
TORONTO, CANADA - Cynapsus Therapeutics Inc. (CTH: TSX-V) (CYNAF: OTCQX), a specialty pharmaceutical company, today announced positive data from its recently completed CTH-104 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 for the acute rescue of "off" motor symptoms of Parkinson's disease.
Mr. Anthony Giovinazzo, President and CEO of Cynapsus commented, "The results from the CTH-104 study in human healthy volunteers are very important as we move forward with testing APL-130277 in Parkinson's patients. Not only have we demonstrated dose proportionality of the doses tested in CTH-103 (10mg and 15mg) and CTH-104 (25mg), but we have demonstrated in CTH-104 that the 25mg dose is sustained over an extended period of time (162 minutes) above the minimal efficacious plasma concentration of apomorphine (approximately 3ng/ml), which is believed to be a level demonstrating symptomatic relief of "off" symptoms. Importantly, we believe we are closer to our goal of being able to provide neurologists and movement disorder specialists with a range of doses that are needed to treat their patients experiencing "off" episodes. We look forward to moving on to our next clinical study (CTH-105) in patients with Parkinson's disease who are naïve to the use of apomorphine and who experience at least one daily "off" episode."
Dr. Albert Agro, Chief Medical Officer at Cynapsus, also commented: "The pharmacokinetic data we have gathered to date not only supports delivery of our formulation by the sublingual route, but also gives us confidence that our formulation may offer several clinically important benefits. We look forward to demonstrating the effectiveness of our drug in Parkinson's patients. "
CTH-104 Key Findings
The CTH-104 study was a single dose, single arm, placebo-controlled, healthy volunteer pharmacokinetic study, which was designed to examine the pharmacokinetic profile of the 25mg dose of APL-130277. In total, 13 subjects completed the study (11 active and 2 placebo). The following are the key findings of the CTH-104 study, which are also compared to the results of the CTH-103 study (See the Corporation's January 13, 2014 Press Release):
2. Time to Maximum Concentration (Tmax) . The Tmax for the 25mg dose of APL-130277 was approximately 40 minutes, which was similar for the 10mg and 15mg doses of APL-130277. The rapid uptake of apomorphine in the APL-130277 strips is comparable to that described in the Apokyn® label (i.e. between 10 and 60 minutes).
3. Maximum Concentration (Cmax). The mean Cmax of the 25mg dose of APL-130277 was greater than the Cmax of the 10mg and 15mg doses, as expected. The pharmacokinetic profiles of all three doses of APL-130277 showed more rounded curves, as compared to the sharper peaks seen following subcutaneous injections of apomorphine.
4. Minimum Efficacious Blood Level (Extrapolated Time-to-On). The minimal efficacious plasma concentration of apomorphine that demonstrates symptomatic relief of "off" symptoms in patients with Parkinson's disease ranges from 1.5ng/ml to 4.5ng/ml. The 25mg dose of APL-130277 achieved within 8 minutes an average minimum threshold concentration of 3ng/ml. The time to reach 3ng/ml in 10mg and 15mg doses of APL-130277 was approximately 13 minutes and 10 minutes, respectively.
*Note: The CTH-103 study was designed as a three-dose (10mg, 15mg and 25mg) active comparator, placebo-controlled, randomized cross-over trial to examine the pharmacokinetic profile of sublingual administered APL-130277 compared to (2mg, 3mg and 4mg) subcutaneous injections of apomorphine in healthy volunteers (See January 13, 2014 Press Release) . 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 intent in the CTH-103 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. As a result, the Corporation completed the CTH-104 study, a single arm, healthy volunteer pharmacokinetic study to look at the 25mg APL-130277 sublingual strip (without a crossover to the injection).
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, 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 U.S. 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:
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 to begin preparation of a FDA 505(b)(2) NDA in 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 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.
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 Corporation'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
CO O & CFO
(416) 703-2449 x253
awilliams@cynapsus.ca
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 March 26, 2014, 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 the TSX Venture Exchange nor the OTCQX International has passed upon the merits of the Offering or approved or disapproved the contents of this press release.
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