Donepezil, the active ingredient in Aricept, is the most widely prescribed medication in a class of Alzheimer's drugs known as cholinesterase inhibitors, and is approved for the treatment of mild, moderate and severe disease. The drug, which is only available in tablet or orally disintegrating tablet form, administered once a day, presents compliance challenges and gastrointestinal side effects.

 

Corium reported preliminary positive results from its recently completed pilot bioequivalence (BE) study demonstrating that its Corplex Donepezil product candidate successfully met the criteria for bioequivalence to oral Aricept (donepezil hydrochloride) using primary pharmacokinetic (PK) endpoints previously established with the U.S. Food and Drug Administration (FDA). Corplex Donepezil is a proprietary once-weekly transdermal patch for delivery of the most commonly prescribed treatment for all stages of Alzheimer’s disease. Corium, which plans to start its pivotal BE study later this year, remains on track to file a Section 505(b)(2) New Drug Application (NDA) for the product candidate in 2018. The pivotal study will be a simpler, two-way crossover design compared to the three- way crossover pilot study.

 

Corium's Corplex system is designed to enable the transdermal delivery of small molecules, many of which have not previously been amenable to transdermal delivery. The technology has been successfully commercialized in Procter & Gamble's Crest Whitestrips products and is being utilized in several proprietary therapeutic products under development.

 

The pilot BE study was a six-month, three-period, randomized crossover study comparing the steady-state pharmacokinetic profiles of once-daily oral Aricept with two Corplex Donepezil transdermal patches that differed only in size. Corium reported that the steady-state PK profiles of the transdermal dosage forms exhibited a close similarity with the oral dosage form PK results, and that the smaller of the two patches met the statistical criteria for bioequivalence at steady-state, based on the primary PK parameters of Cmax (maximum plasma concentration) and AUC (area under the curve). The study, performed at a single trial site, enrolled 60 healthy male and female volunteers ages 20 to 78, with more than 80 percent of the subjects over the age of 40.

 

Both Corplex transdermal treatments were well tolerated, with favorable adhesion, skin safety and gastrointestinal side effect profiles after application of over 500 patches in the course of the study. For example, the incidence of nausea in subjects on the smaller patch was more than four-fold lower than the incidence of nausea with oral Aricept.

 

According to Peter Staple, president and CEO of Corium, the company is pursuing the bioequivalence-based development and regulatory pathway for Corplex Donepezil after receiving positive written feedback on this approach from the FDA in April 2016. The pilot study was designed with the objective of enabling the company to finalize patch size and other key parameters to successfully demonstrate bioequivalence in a pivotal BE study. As he explained, “The pilot study results should help to accelerate talks with partners.”

 

Dr. Parminder “Bobby” Singh, chief technology officer and vice president of research and development of Corium, said, “Based on these results, we can now move forward knowing that we have a product candidate that can meet the bioequivalence-based registration criteria. We are finalizing the scale up and related activities to support the start of our pivotal study this fall, with the objective of filing our NDA in 2018.”

 

“I am encouraged by the rapid clinical development of Corium’s once-weekly transdermal donepezil product,” added Dr. Pierre N. Tariot, co-director of the NIH-funded Alzheimer’s Prevention Initiative and a clinical advisor to Corium. “Given the inherent challenges we face in treating persons with Alzheimer’s, as well as limitations of currently available medications, I am hopeful that the transdermal approach can afford improved compliance and potential clinical benefits that could truly matter to both our patients and their families.”

 

Staple concuded, “This is an important new treatment option for patients with Alzheimer’s through all stages of the disease.”