Cynapsus reported that 14 of the 16 Parkinson's disease patients responded positively in the Phase II trial of its reformulated thin-film strip version of the drug apomorphine, dubbed APL-130277, for the treatment of "off" episodes.
Off episodes limit the mobility of Parkinson's patients and cause the disease's symptoms to reemerge in patients on the mainline Parkinson's treatment levodopa, Cynapsus CEO Anthony Giovinazzo explained during last week's conference call with investors, saying, "the incidence of off episodes is relatively high in patients with Parkinson's who have a history of long-term oral levodopa use, and it increases with the length of time that they are on levodopa."
All but two of the patients in the study were converted to the "on" state, meaning they were once again able to move and communicate. Clinical improvements were noticed as early as 10 minutes after administration and lasted longer than 90 minutes.
The maximum mean change in the patients' Unified Parkinson's Disease Rating Scale (UPDRS) part III score was 18.4 points, Cynapsus officials said. After 90 minutes, the mean change was about 13 points, with the maximum mean change being reached at about 45 minutes, after which the effect of the drug begins to wear off, according to the investor presentation. The UPDRS scale has a maximum score of 132, with a higher score indicating more impairment.
Giovinazzo stressed that the new delivery method is the candidate's main advantage over Apokyn, the injectable version of apomorphine currently offered by Britannia Pharmaceuticals.
"It's ease of retrieval and ease of administration that we think are primary benefits, in addition to a comparable drug efficacy profile," he said. "Many patients experiencing off states lack the manual dexterity required for multiple daily injections," he said, adding that APL-130277 also eliminates needle pain and problems associated with needle aversion.
During the conference call Chief Scientific Officer Dr. Albert Agro said that Apokyn achieved a maximum mean change of 24 points on the UPDRS, indicating that it had a greater effect on patient outcomes than Cynapsus's potential sublingual challenger, APL-130277.
One of the primary objectives of the study was determining the optimal dosage. The subjects were tested at 5 doses ranging from 10 to 30 milligrams. Three of the patients converted to the on state at the 10-mg dose. Agro said during the investor call that the nonresponders likely needed a higher dose. "With every drug there are patients that just don't respond. In this instance I don't think that was case. My sense is that they would probably have responded to a little bit of a higher dose. That's going to be investigated." The company may increase the maximum dosage in the upcoming Phase III trial by offering two strips to achieve a dosage of 35 or 40 mg.
Another concern was the candidate's adverse events and side effects. Three of the 16 patients experienced nausea, the company said during the conference call.
Soon, Cynapsus will have an "end of Phase II meeting" with the FDA to discuss the results and receive guidance on the type and size of remaining clinical studies needed for product approval, Giovinazzo said. A larger Phase III study is planned to test safety and efficacy. Participants will take the candidate home for "on demand" use to test the product in a real-world setting, Giovinazzo said. The company expects to file a New Drug Application for FDA approval in 2016.
Meanwhile, competitor Civitas Therapeutics is working on an inhaled version of levodopa that it says helps prevent off episodes by improving drug absorption. Civitas was recently acquired by Acorda Therapeutics ($ACOR) for $525 million.
- listen to the conference call (reg. req.) and/or view the presentation slides
- read the release