Corium is advancing two products through the clinic for the treatment of Alzheimer’s disease: CorplexTM Donepezil and Corplex Memantine.
A once-weekly treatment for Alzheimer’s disease, our lead product is a transdermal formulation of donepezil, the active ingredient in Aricept®, which is one of the most commonly prescribed treatments for the care of patients with Alzheimer’s disease.
In 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, we demonstrated that the steady-state PK profiles of the transdermal dosage forms exhibited a close similarity with the oral dosage form PK results. In fact, 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). We are planning to use the data from this study as the sole basis for establishing bioequivalence.
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 drug-related nausea in subjects on the smaller patch was more than six-fold lower than the incidence of nausea with oral Aricept.
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. We are on track to file a Section 505(b)(2) New Drug Application (NDA) for this product candidate in the first calendar quarter of 2019, which we expect would lead to a PDUFA date in the fourth calendar quarter of 2019.
Important potential benefits of Corplex Donepezil
- Improved adherence related to the simple once-weekly dosing schedule. This is particularly important as the disease progresses, when patients can become increasingly confused and combative, and may develop swallowing difficulties; and
- Reduced rates of gastrointestinal (GI) side effects such as nausea, vomiting and weight loss by avoiding the GI tract.
We are also developing a once-weekly transdermal formulation of memantine, the active ingredient in Namenda XR®. In early 2016, we announced interim results of our Phase 1 clinical study, which demonstrated sustained and controlled delivery of memantine, with a comparable PK profile to oral Namenda XR. The FDA has agreed 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) is the most widely prescribed medication in a class of Alzheimer’s drugs known as cholinesterase inhibitors, which are known to boost the levels of the neurotransmitter acetylcholine in the brain and slow declines in memory and cognition. This class of medications also includes Exelon® (rivastigmine), the only currently approved patch for Alzheimer’s, which is administered once daily. According to IMS, in 2015 there were approximately five times as many units of donepezil sold in the United States as units of Exelon. Despite the lower number of units sold – and the presence of an oral generic version since 2010 – the Exelon patch had peak sales in excess of $1.1 billion and 2015 global sales approaching $900 million.
Corplex Donepezil is designed to deliver the dominant agent for Alzheimer’s in a simple, convenient once-weekly transdermal patch, and we believe this transdermal product candidate can provide an opportunity for improved adherence to therapy, as well as an improved tolerability profile.
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 as the disease progresses. Per IMS, global sales of memantine in 2015 were more than $2.5 billion.