Cynapsus Therapeutics' sublingually delivered reformulation of the drug used to treat advanced Parkinson's disease cleared an initial clinical hurdle, the company said April 24.
The medication would be the first noninjectable apomorphine therapy. The product, dubbed APL-130277, is absorbed directly into the bloodstream from under the tongue, said Cynapsus Chief Medical Officer Dr. Albert Agro.
Apomorphine is a dopamine agonist used to treat patients with Parkinson's disease who suffer from debilitating "off" episodes, during which they become immobile. The injectable version of the drug is marketed as Apokyn in the U.S. by Britannia Pharmaceuticals.
Apomorphine is used as an as-needed "rescue" supplement to the mainline Parkinson's treatment levodopa, the absorption of which by the human body is a bit unpredictable, Agro said. "'Off' episodes begin when the levodopa or enzyme inhibitors enter the bloodstream too slowly, or wear off quickly, or just do not enter the bloodstream sufficiently at all," he explained. In addition, he said, levodopa typically diminishes in effectiveness after about 5 years of use.
Companies are exploring new ways of delivering levodopa as well. In a related development, also covered in this week's edition of FierceDrugDelivery, Civitas Therapeutics announced that it had made progress in its Phase II clinical trial of an inhaled levodopa formulation, which it claims solves the problem of variable drug concentration that is inherent to the oral delivery method.
Cynapsus is focused on improving the delivery of apomorphine. Agro said that 85% of Apokyn patients have a site injection reaction to the medication and must continuously change the injection site. APL-130277 contains a buffer that protects the patient from the acidic properties of the medication, Agro said.
Another advantage of APL-130277 is ease of use, he said, pointing out that delivering an injection prior to the onset of an off episode can be a challenge for Parkinson's patients.
The 25-mg sublingual strip dose of apomorphine exhibited many important qualities in an early-stage, single-dose, single-arm study of 13 healthy patients, Cynapsus said in a statement. These include dose proportionality and side effects consistent with the previously known systemic effects of apomorphine in the body, including dizziness and nausea. The minimum efficacious blood level of 3 ng/ml was achieved in 7-13 minutes, Agro said.
Cynapsus plans 5 more trials prior to filing a New Drug Application with the FDA in 2016. Agro said that the company is discussing the parameters of its CTH-301 safety study on 150 patients with the FDA. It will last at least 6 months.
Meanwhile, Civitas Therapeutics said that its inhaled levodopa formulation, CVT-301, met its primary endpoint in a Phase II study.
- read the release
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Cynapsus' sublingual strip for severe Parkinson's reduces side effects in a study
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