Corium is advancing two clinical-stage investigational products for the treatment of Alzheimer’s disease: Corplex™ Donepezil and Corplex Memantine.
Our lead investigational product is being designed as a once-weekly treatment for Alzheimer’s disease and is a transdermal formulation of donepezil, the active ingredient in Aricept®. Donepezil is the most commonly prescribed treatment for patients with Alzheimer’s disease.
We have conducted a six-month, three-period, randomized crossover study comparing the steady-state pharmacokinetic (PK) profiles of once-daily oral Aricept with two Corplex Donepezil transdermal patches that differed only in size. This study of healthy volunteers was designed to determine whether the steady-state PK profiles of the transdermal dosage forms would be biologically equivalent to the oral dosage form PK profiles. We are planning to use the data from this study as the sole basis for establishing bioequivalence.
By delivering donepezil through the skin, Corplex Donepezil was designed to avoid absorption of donepezil in the GI tract. The product was also designed to be worn for seven days with consistent adhesion.
We are pursuing a bioequivalence-based development and regulatory pathway for Corplex Donepezil after receiving positive written feedback on this approach from the FDA in April 2016 and September 2017.
Important potential benefits of transdermal drug delivery, which could have particular relevance to the Alzheimer’s population
- Less frequent dosing due to once-weekly application;
- Avoids gastrointestinal (GI) metabolism, which could lead to fewer GI side effects; and
- Improved delivery for patients with swallowing difficulties
We are also developing a once-weekly transdermal formulation of memantine, the active ingredient in Namenda XR®. This investigational product is being developed to provide sustained and controlled delivery of memantine, with a comparable PK profile to oral Namenda XR. The FDA has provided positive written feedback indicating that the bioequivalence-based development and regulatory path that we are pursuing for Corplex Donepezil is also available for Corplex Memantine.
Alzheimer’s Disease Market Opportunity
Alzheimer’s disease is a progressive brain disorder in which brain cells degenerate and die, causing a steady decline in memory and mental function. An estimated 5.7 million Americans suffered from Alzheimer’s disease in 2018; by 2050, this number is expected to approach 14 million. Alzheimer’s disease is the most common cause of dementia and the incidence of non-compliance and swallowing issues increase as the disease progresses.
Approved for all stages of Alzheimer’s disease, donepezil (the active ingredient in Aricept) tablets are the most widely prescribed medication in a class of Alzheimer’s drugs known as cholinesterase inhibitors, which are thought to work through boosting the levels of the neurotransmitter acetylcholine in the brain to impact the signs and symptoms related to memory and cognition. This class of medications also includes rivastigmine, the only drug currently approved in patch form for the treatment of Alzheimer’s, which is administered once daily and is available under the brand name Exelon® and as a generic. Prior to the loss of patent expiry, the Exelon patch had peak global sales in excess of $1.1 billion, despite the availability of an oral generic version of the molecule for several years.
Memantine (the active ingredient in Namenda® and Namenda XR), is the second most prescribed medication for Alzheimer’s disease. Only available in oral form, it is approved for the treatment of moderate to severe Alzheimer’s disease. Memantine has a distinct mechanism of action from donepezil and these two medications are frequently prescribed together. Per IQVIA, peak global sales of memantine were more than $3 billion.
The safety and efficacy of the products under investigation have not been established. There is no assurance that any of these investigational products will receive health authority approval or become commercially available in any country.