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. We have demonstrated sustained and controlled delivery of donepezil over a one-week period, with a pharmacokinetic (PK) profile comparable to oral Aricept taken daily for seven days. This patch also demonstrated excellent skin tolerability.
Based on guidance from the FDA, Corium is pursuing a bioequivalence-based development and regulatory path for Corplex Donepezil. This means that the key clinical studies will be based on establishing that Corium’s transdermal product provides statistically equivalent blood concentrations of donepezil compared to the oral dosage form at relevant time points. With this approach, we are able to complete our clinical trials in healthy volunteers, without the need to perform more costly and time-consuming efficacy studies.
This approach allows for a streamlined development process for Corplex Donepezil compared to a typical transdermal product, with a potential launch in 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 5.1 million Americans suffered from Alzheimer’s disease in 2015; by 2025, this number is expected to exceed 7.1 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.