June 25, 2015
APL-130277, Sublingual Apomorphine, for On-Demand Treatment of OFF Episodes Associated with Parkinson's Disease
TORONTO – (Marketwired) – Cynapsus Therapeutics Inc. (NASDAQ: CYNA) (TSX: CTH) (the "Company") today announced that it presented data from clinical trials of APL-130277, a sublingual apomorphine thin film under development for the on-demand treatment of OFF episodes associated with Parkinson's disease (PD). Data from the Company's CTH-105, CTH-104 and CTH-103 clinical studies, presented at the 19th International Congress of Parkinson's Disease and Movement Disorders (MDS) in San Diego, California, showed APL-130277 significantly improved PD symptoms (as measured by MDS-UPDRS Part III), rapidly turned patients from the OFF to ON state and was generally safe and well tolerated.
"Phase 1 and Phase 2 data presented at the Congress demonstrated that APL-130277 can achieve the appropriate apomorphine plasma levels needed to rapidly and reliably convert a patient from the OFF to the ON state. In addition, APL-130277 was safe and effective for the acute treatment of OFF episodes in PD patients," said Jordan Dubow, M.D., Vice President, Medical Affairs, Cynapsus Therapeutics. "These data lead in to our Phase 3 pivotal studies to assess the efficacy, safety and tolerability of APL-130277 for the acute, on-demand management of OFF episodes."
Presentations at MDS included:
Efficacy of Sublingual Apomorphine (APL-130277) for the Treatment of OFF Episodes in Patients with Parkinson's disease; Hauser et al.
• CTH-105 was a Phase 2 open-label multicenter study in which APL-130277 was assessed in 19 patients with PD who experienced OFF episodes, with a total duration of at least two hours of OFF episodes daily.
• Of the 19 total patients dosed, 15 achieved a full ON response. Of the four non-responders, two were dosed incorrectly and two were dosed up to the maximum available dose (30mg).
• Sublingually administered APL-130277 rapidly converted PD patients from the morning OFF state to the full ON state with 100% of responders turning fully ON within 30 minutes and 40% within 15 minutes.
• APL-130277 provided, rapid, clinically meaningful and statistically significant improvement in motor function as assessed by MDS-UPDRS Part III score at all time points assessed (i.e. 15, 30, 45, 60 and 90 minutes) with a mean maximal improvement of 18.9 points in the intent to treat population.
• Thirteen of the 15 patients that turned ON remained ON for at least 30 minutes, nine of whom remained ON for at least 60 minutes, with a mean duration of ON of over 50 minutes.
• The percentage change in MDS-UPDRS Part III was approximately 30% or greater at all time points measured, with a maximum mean percentage change at any time point of 45.6% for the intent to treat population. Mean percentage change of approximately 30% is generally considered a clinically meaningful level at which point patients turn ON.
Safety of Sublingual Apomorphine (APL-130277) for the Treatment of OFF Episodes in Patients with Parkinson's disease; Isaacson et al.
• In the CTH-105 study, a total of 77 doses of APL-130277 were administered to the 19 patients who completed dosing.
• APL-130277 was safe and well-tolerated by all of the PD patients in the study.
• Rates of adverse events (AEs) were similar to other dopamine agonists.
• There were no related serious AEs, no AEs of local oral mucosal irritation, and no subjects discontinued due to an AE or any other reason.
Pharmacokinetics, Safety and Tolerability of High-dose Sub-lingually Administered APL-130277 in Healthy Volunteers; Agro et al.
• CTH-104 was a single-center, Phase 1 study that evaluated the pharmacokinetic (PK) profile, safety and tolerability of a single dose of APL-130277 25mg in healthy volunteers. Eleven subjects were dosed with APL-130277 25mg and two with placebo.
• In healthy volunteers, the higher dose of APL-130277 (25mg) administered sublingually demonstrated a favorable PK profile to support a rapid and sustained effect for acute relief of OFF episodes in PD patients.
• Time to reach the known minimum efficacious plasma apomorphine concentration was achieved in under 10 minutes and apomorphine levels were maintained above this concentration for over 2.5 hours.
• PK results demonstrated dose proportionality to lower doses and the PK curve remained rounded.
• The AEs reported were mild to moderate in severity with no serious AEs.
Pharmacokinetics, Safety and Tolerability of Sublingually Administered APL-130277 Compared to Subcutaneous Apomorphine in Healthy Volunteers; Agro et al.
• CTH-103 was a single-center, Phase 1 crossover study that evaluated the PK profile, safety and tolerability of two doses of APL-130277 (10mg and 15mg) compared to subcutaneous apomorphine in healthy volunteers (2mg and 3mg).
• Sublingually administered APL-130277 reached known therapeutic apomorphine plasma levels comparable to subcutaneous apomorphine with a longer duration over the minimum efficacious plasma concentration.
• APL-130277 demonstrated a more rounded peak, lower maximal concentration and less steep rise to maximal concentration compared to subcutaneous apomorphine, leading to less dopaminergic AEs. This was evident as a higher incidence of nausea and vomiting was reported when subjects were given the subcutaneous apomorphine versus APL-130277.
• APL-130277 was demonstrated to be safe and well-tolerated and no subjects discontinued treatment with APL-130277 due to an AE.
Cynapsus is a specialty central nervous system pharmaceutical company developing and preparing to commercialize a Phase 3, fast-acting, easy-to-use, sublingual thin film for the on-demand turning ON of debilitating OFF episodes associated with Parkinson's disease (PD).
President and CEO
(416) 703-2449 x225
COO & CFO
(416) 703-2449 x253
Russo Partners LLC
This announcement contains "forward-looking statements" within the meaning of applicable securities laws. These forward-looking statements include information about possible or assumed future results of the Company's business, financial condition, results of operations, liquidity, plans and objectives. In some cases, you can identify forward-looking statements by terminology such as "believe," "may," "estimate," "continue," "anticipate," "intend," "should," "plan," "expect," "predict," "potential," or the negative of these terms or other similar expressions. These forward-looking statements are based on the Company's current expectations and beliefs and inherently involve significant risks and uncertainties. Actual results and the timing of events could differ from those anticipated in such forward-looking statements as a result of risks and uncertainties, in include, but are not limited to those factors identified under the caption "Risk Factors" in the Company's filings and reports in the United States with the United States Securities and Exchange Commission (the "SEC") available on the SEC's web site, and in Canada with the various Canadian securities regulators, which are available online at www.sedar.com. Furthermore, unless otherwise stated, the forward-looking statements contained in this press release are made as of the date of this press release, and the Company has no intention and undertakes no obligation to update or revise any forward-looking statements, whether as a result of new information, future events, changes or otherwise, except as required by law.
Neither the NASDAQ nor the TSX has approved or disapproved of the contents of this press release.