FDA Approves Weekly Patch to Treat Alzheimer's-Related Dementia

The U.S. Food and Drug Administration (FDA) has approved a weekly skin patch used to treat symptoms of Alzheimer's-related dementia. The treatment is a patch formulation of the oral drug donepezil (Aricept), which has been available for many years and is one of the most commonly prescribed drugs for patients with Alzheimer's disease.

The new medication, which will be sold under the brand name Adlarity, is not the first skin patch approved for Alzheimer's disease, but it is the first to be administered once weekly. This regimen is expected to benefit certain patients.

"It would be better for forgetful patients who have to remember taking their medications or patients who have paranoia and refuse to take medications, for example," neurologist Riddhi Patira, MD, an assistant professor and investigator at the University of Pittsburgh Alzheimer's Disease Research Center, told Health.

Another advantage of the patch is the potential for fewer side effects. According to Dr. Patira, the most common adverse reactions to the oral donepezil are gastrointestinal problems, such as nausea and diarrhea. Those should not be completely eliminated, as they are directly caused by the drug's mechanism of action, she said. But they will likely be less severe with the skin patch, compared to the oral formulation.

How It Works

Adlarity can be placed directly on a patient's back, thigh, or buttocks, according to a press release from Corium, Inc., the drug's maker. The once-weekly patch delivers a continuous and consistent dose of donepezil through the skin.

Once in the body, the transdermal version of donepezil works similarly to the oral formulation of the drug. "What donepezil does, as I frequently tell patients and their families, is that it works to keep the acetylcholine—a molecule that we all have in our brains—longer to help with attention and memory," geriatrician Mia Yang, MD, an assistant professor with Atrium Health Wake Forest Baptist in North Carolina, and a researcher in the Wake Forest Alzheimer's Disease Research Center, told Health. "But certainly, it is not a cure for Alzheimer's disease or other types of dementia."

Acetylcholine is a neurotransmitter that plays an important role in memory and thinking. Patients with Alzheimer's disease usually have less of that molecule than normal. As a cholinesterase inhibitor, donepezil works by inhibiting cholinesterase, an enzyme that breaks down acetylcholine, aiming to preserve the patient's level of this neurotransmitter.

Because donepezil doesn't target anything specific to Alzheimer's disease (we all have acetylcholine in our brains), it is expected to work for other types of dementia as well. The only exception is frontotemporal dementia (FTD). "Donepezil has been studied in double-blinded, randomized clinical trials in FTD patients and it doesn't help, it actually worsens the behavior," Dr. Patira said. "And this is pretty important because, when my patients come to me, sometimes they don't have a specific diagnosis, they are just labeled as dementia."

Drug Availability

According to Corium, Inc., the new patch will be commercially available in early fall 2022. But doctors are skeptical that the new product will be covered by health insurance, based on previous experiences.

Rivastigmine (Exelon) is a medication of the same class as donepezil that is already available as a skin patch (the difference is that it has a once-daily, instead of once-weekly, regimen). "Usually, it's rather hard to get people approved from their insurance company to get the rivastigmine patch," said Dr. Yang.

According to Dr. Yang, she normally has to document that the patient had side effects from the oral version of rivastigmine to justify the request for the patch version. Dr. Patira has had a similar experience. "Getting the rivastigmine patch has been a battle with insurance companies," she said.

Other Alzheimer’s Disease Treatments

There are very few medication options to treat Alzheimer's disease, and their efficacy is modest, according to experts. "These medications are not magic bullets," Dr. Patira said. In addition to donepezil, there are two other cholinesterase inhibitors: galantamine and rivastigmine (the one that also has a patch version). They all work very similarly. There is also a drug with a different mechanism called memantine, which works by regulating glutamate, a neurotransmitter that, in excess, may lead to brain cell death.

While these drugs can only help with Alzheimer's symptoms, without targeting the cause of the disease, patients and families always hope for a curative approach. In June 2021, the FDA approved the first Alzheimer's drug that is potentially disease-modifying. Aducanumab (Aduhelm) is a monoclonal antibody treatment that targets harmful protein deposits, called amyloid plaques, seen in Alzheimer's patients' brains. But the many controversies around it make part of the scientific community skeptical of its efficacy.

According to Dr. Yang, one of the issues is that the drug would only work, in theory, in patients who have amyloid plaques in their brains. Currently, the amyloid PET scan is not widely available.

Another issue is that only one of two clinical trials done by maker Biogen was mildly positive, the other was negative. "Even in the group that showed the marginal benefit, there really was only a 0.39-point improvement out of an 18-point scale in the group that got the high dose infusion compared to the placebo. So, the size of the clinical benefit was very, very small," Dr. Yang said. Potential harmful side effects and the high cost of the drug also complicate its potential use.

Apart from aducanumab, there are other drugs in development that target amyloid. "That debate has a huge scientific value, of whether those drugs are going to prove the amyloid theory or disregard it," Dr. Patira said.

Current Treatments May Lead to Difficult Decisions

When it comes to donepezil and similar available drugs, experts acknowledge that it is difficult to assess how much they are actually benefiting the patient. "I usually tell patients and their families that, once people are on the medication, it can be difficult to say if the trajectory of the disease would be different if they were not on the medicine," Dr. Yang said. "I paint the expectation that most people who are on donepezil will not necessarily see a noticeable improvement in their memory, only a minority of people will."

Dr. Patira noted that, because of the modest efficacy, some providers don't even offer these medications to patients. "I do usually offer them to follow the standard of care," Dr. Patira said. "We discuss that there are very limited options and, even though we discuss that they might not have many benefits, patients still want to try."

Because it is difficult to measure if the medications are working, it is also unclear when patients should stop taking them, Dr. Yang said. If patients have side effects – in addition to diarrhea, they may also experience lower heart rate, dizziness, vivid nightmares, and lack of appetite – providers will usually suspend the use. "But if they continue without any side effects, then the literature on when to stop these medications is really not clear," Dr. Yang said.

As the disease progresses and the patient starts experiencing other health issues or losing weight, Dr. Yang suggested that it might be the time to discuss the possibility of stopping. "I generally tell people that they're not missing out on a miracle pill if they decide not to take it," she said. "I do have a handful of patients that, even though they have dementia, choose not to take donepezil or any other similar medicines. Because, one, they're already on a lot of other medicines. And, two, they know that the benefit is marginal."