Sunovion Pharmaceuticals Inc.'s $635 million buy of Cynapsus Therapeutics Inc. gained new validation with the success of a pivotal phase III trial testing the object of the deal, a sublingual version of the antiparkinsonian drug apomorphine. Participants taking the drug showed a statistically significant mean reduction in "off" episodes, as measured by a commonly used assessment of motor function in Parkinson's patients, meeting the trial's primary endpoint. The study also met its key secondary endpoint, showing that a statistically significant greater percentage of people treated with the drug had a patient-rated full "on" response vs. those in the placebo group.
Sunovion, a subsidiary of Sumitomo Dainippon Pharma Co. Ltd., said the results supported an anticipated spring 2018 filing of its new drug application (NDA) for the candidate, APL-130277. If successful, the compound is expected by analysts to generate revenue of about $82 million in 2020, meaning it could play a small but contributing role to helping Sumitomo Dainippon get past an expected dip in net sales in fiscal 2019, when the full effects of Latuda (lurasidone) exclusivity loss are expected to take hold. It could also help the company answer growing pressure in Japan to focus on innovative therapies. (See BioWorld, Jan. 10, 2018.)
Apomorphine is the only molecule approved for on-demand, intermittent treatment of off episodes for advanced PD patients, but in the U.S. is currently approved only as a subcutaneous injection, sold as Apokyn from US Worldmeds LLC. Sunovion's sublingual formulation is designed to offer a new option that can be used first thing in the morning, and up to five times throughout the day. In August 2016, the FDA granted it fast track status.
In CTH-300, the 12-week phase III study reported Tuesday, 109 adults with levodopa-responsive PD complicated by off episodes were randomized to receive either APL-130277 or placebo. It met its primary endpoint by showing that individuals with off episodes who received the drug demonstrated a statistically significant mean reduction in the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III score from pre-dose to 30 minutes after dosing at week 12 vs. those in the placebo group, with effects persisting until the last observed time point at 90 minutes. The difference in MDS-UPDRS Part III score change from baseline 30 minutes after dosing between apomorphine sublingual film and placebo was 7.6 (p=0.0002).
The study also met its key secondary endpoint, showing that a statistically significant greater percentage of people treated with apomorphine sublingual film (35 percent predicted response rate) had a patient-rated full on response within 30 minutes after dosing at week 12 compared with the placebo group (16 percent predicted response rate).
Sunovion said that the drug was generally well-tolerated, though 27 percent of trial subjects reported nausea. Other commonly reported treatment-emergent adverse events during both the titration and maintenance treatment phases were somnolence (14.9 percent), dizziness (14.2 percent), yawning (12.8 percent) and headache (9.2 percent).
Though an NDA filing for APL-130277 had initially been slated for the first half of 2017, after Sunovion's team had the opportunity to review the clinical development plan for the candidate, plans changed, Kristina Coppola, Sunovion's associate director of portfolio communications told BioWorld. Sunovion's team decided to re-open enrollment in CTH-300, which had been previously closed by Cynapsus, thus extending the trial, she said. (See BioWorld Today, Sept. 2, 2016.)
With CTH-300 complete, several studies of APL-130277 remain underway. CTH-301 is another phase III trial seeking to evaluate the long-term safety and tolerability of apomorphine sublingual film in up to 200 patients with PD. It is a long-term, open-label, single-arm study involving PD patients who have at least one off episode per day, with total off time of at least two hours per day. People who completed other studies involving apomorphine sublingual film are eligible to enter CTH-301, Coppola said.
Another study, CTH-302, is a four-week, open-label, active comparator European registration study of the drug that includes about 90 patients. Additionally, Sunovion is evaluating the longer-term plans for the apomorphine sublingual film clinical development program, Coppola said.
In addition to Sunovion, at least two other companies appear to be working on easier-to-take formulations of apomorphine for the potential treatment of off episodes in PD: Kasterlee from Belgium-based Innotesto BVBA and Gujarat, India-based Renown Pharma Ltd. Innotesto is investigating Aporon, a formulation of apomorphine thought to be a buccal spray that is listed as being in preclinical development. Renown Pharma is developing a sublingual spray formulation of the drug. In March 2017, it reported results from a small phase I study in which it appeared to match the characteristics of injected apomorphine.