Cynapsus ($CYNA) kicked off patient enrollment in its Phase III clinical trial of sublingual apomorphine for Parkinson's patients who suffer from "off episodes," such as those for whom levodopa alone is inadequate.
The current formulation of apomorphine is currently available as a subcutaneous injectable, dubbed Apokyn. But the supplemental "rescue" medication is plagued by practical delivery issues, such as the need for a skilled nurse to carry out its 15-step administration process, perform titration and contend with injection-site reactions. Note that Parkinson's patients in the "off" state suffer from severely limited mobility, adding to the complications and making self-administration of the injectable impossible.
Despite those limitations, Cynapsus CEO Anthony Giovinazzo told FierceDrugDelivery in an interview that "apomorphine is the only dopamine agonist that is capable of turning a patient from off to on very quickly." Previous trials have shown patient improvement in 10 minutes following administration. The CEO believes Cynapsus is close to succeeding at developing a new formulation and improved administration method of the dopamine agonist, a task which several other have attempted unsuccessfully.
Cynapsus' under-the-tongue formulation is simpler to use and can be self-administered, meaning if approved, it should improve upon Apokyn's market penetration rate of about 5% of the potential market. Zacks Small Cap Research predicts it will be used in one-fourth of severe Parkinson's patients with off issues by 2024, assuming approval.
To that end, the company announced its first patient in the sublingual candidate's pivotal Phase III trial, which will eventually enroll about 126 Parkinson's patients who have at least one off episode a day, with total off time of least two hours per day. The primary endpoint will be mean change in MDS-UPDRS Part III score 30 minutes after dosing at week 12.
"There are many patients, early, mid and late, who qualify," Giovinazzo said, estimating that at least 400,000 patients meet the criteria for time spent in off episodes. In addition to the "wearing off" affect, which makes levodopa less effective over time, gastric emptying and protein competition during drug delivery and absorption mean that some patients have to wait one or two hours before levodopa's affects are felt, the CEO said.
The secondary endpoint will be the percentage of patients who convert from the off to the on state at or before 30 minutes of dosing, also at week 12.
Phase III commences after promising Phase I and II data was presented at the 19th International Congress of Parkinson's Disease and Movement Disorder in San Diego.
In Phase II, 15 of 19 patients had a fully on response. Of the four nonresponders, two were dosed incorrectly and the others were dosed up to the maximum available dose (30 mg), Cynapsus said in a release. The average length of on time was more than 50 minutes.
In addition, the maximum change in the MDS-UPDRS Part III score at any time point was 45.6%, above the clinically meaningful level of 30%. The score was assessed at 12, 30, 45, 60 and 90 minutes after administration of the candidate.
And on the safety side, the studies detected no serious adverse events, or side effects related local oral mucosal administration, which would be a result of the sublingual delivery method, Cnyapsus said.
Now, the candidate is moving on to Phase III.
Zacks says demand for an easy-to-administer formulation of apomorphine is high because levodopa begins to lose effectiveness after about 5 years, with almost all patients suffering from off episodes after 10 years. And the rate of dyskinesia is 50% after 5 years on levodopa, and 100% after 10 years.
The investment firm estimates peak U.S. annual sales of $680 million, and total sales of about $1.2 billion by 2025. It predicts the sublingual therapy will fare better than Acorda's inhaled levodopa candidate, which aims to improve on the aforementioned problems of the first-line treatment.
Neuroderm has a Phase I apomorphine-based candidate in its pipeline. The company aims to deliver the drug via a belt or patch pump to patients with severe Parkinson's.
Cynapsus IPOed at $16 on June 18, raising $72.5 million. It now trades close to $17.
- read the release about Phase III enrollment
- here's the release about Phase II and Phase I results
- get more from Zacks' analysts
Editor's Note: This article corrects a previous statement that the candidate is intended for use as a second-line (rather than a rescue or supplemental) therapy. Additional comments from the Cynapsus CEO have also been added.