MENLO PARK, Calif.—In its ongoing work of developing and commercializing specialty transdermal products, Corium International Inc. shared positive news recently, with top-line interim results from a Phase 1 clinical study of its Corplex Donepezil transdermal delivery system for the treatment of mild, moderate and severe dementia of the Alzheimer’s type. This product candidate is meant to offer an alternative for sustained, controlled drug delivery in a convenient, once-weekly dosage form.
Corium’s Corplex system is a novel commercial-stage platform technology designed to enable transdermal delivery of small molecules, many of which have not previously been suitable for that delivery method. The company’s transdermal and transmucosal systems are adaptable for use in a variety of drug categories and indications, and they could reduce the amount of active ingredient needed in transdermal products. The transdermal patches can enable efficient drug delivery, and stick to either wet or dry surfaces for an extended period of time.
Donepezil, the active ingredient in Eisai’s Aricept, is currently the most prescribed medicine among cholinesterase inhibitors, and is approved for the treatment of mild, moderate and severe dementia associated with Alzheimer’s disease. At present, it is only available as a once-daily tablet, and known side effects include nausea, vomiting and loss of appetite.
The Phase 1 study in question consisted of nine healthy volunteers ages 50 to 80. While the trial initially included a 10 mg oral dose, subjects experienced adverse events in line with the oral product labeling, and as such, the 10 mg oral dosing was discontinued, with the 5 mg oral dose used as the sole comparator. Participants received two treatments: a once-weekly Corplex patch targeted to deliver 5 mg per day of donepezil, and a once-daily Aricept 5 mg tablet administered consecutively for seven days. The primary objective was to determine the pharmacokinetics of single-dose, once-weekly Corplex Donepezil compared to daily oral Aricept, with secondary objectives of safety and skin tolerability.
The study found that after a single application of the once-weekly Corplex Donepezil patch, plasma concentrations approached steady state by day seven, with an average plasma concentration higher than that of 5 mg oral Aricept. The plasma concentration was also approximately 70 percent of that expected from 10 mg oral Aricept. The concentrations demonstrated sustained, controlled drug delivery, supporting a once-weekly dosing regimen compared to a daily regimen.
Corium noted that “Active metabolite formation was minimal and similar for both the transdermal and oral routes of administration, indicating that there were no changes in metabolite concentration in plasma associated with drug absorption through the skin.” Skin tolerability was acceptable, with no systemic adverse events unique to the transdermal delivery. The company concluded that these result support further clinical development of Corplex Donepezil, including optimizing it for a once-weekly administration of 10 mg per day.
“We are very pleased with the Phase 1 pharmacokinetic results, which provide a solid basis for advancing Corplex Donepezil into further clinical development,” Dr. Parminder “Bobby” Singh, chief technology officer and vice president of research and development at Corium, remarked in a statement. “The clinical data demonstrate the potential for a once-weekly donepezil patch that reliably delivers sustained and controlled pharmacokinetics comparable to the daily oral administration of Aricept. These results further validate the ability of Corium’s Corplex platform to administer difficult to deliver drugs across the skin, and to advance the breadth of our transdermal pipeline.”
This isn’t the only positive news for Corium in Alzheimer’s disease lately. Toward the end of February, the company shared positive top-line interim results from a Phase 1 clinical study of its Corplex Memantine transdermal delivery system for Alzheimer’s disease. The study is assessing the pharmacokinetics, safety and tolerability of Corplex Memantine. The patch formulation demonstrated sustained, controlled delivery of memantine, supporting further clinical development for a three-day patch and potentially a once-weekly dosing regimen. Corium noted that some subjects saw significant skin irritation in the pharmacokinetic study, but “acceptable skin tolerability was observed in a follow-on wear study for a three-day patch, using a modified application procedure and configuration.”
Corium also shared unaudited financial results from operations for its first fiscal quarter of 2016, ended Dec. 31, 2015. The company saw total revenues of $7.5 million, down from $9.8 million in Q1 fiscal 2015. Corium saw a net loss of $9.4 million, or 42 cents per share, for the quarter.
“The first quarter has been a particularly productive one for Corium, as we have advanced two product candidates in our CNS portfolio into the clinic, and have worked with our partners in progressing studies that are key to their programs … With this portfolio of opportunities, we are accelerating our growth and progress in advancing important new transdermal therapeutics. 2016 will be a year of significant milestones for Corium,” Peter D. Staple, president and CEO of Corium, said in a press release announcing Corium’s quarterly results.
