What is the latest on pharmaceuticals for the treatment of dementia?
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A brief conversation with Stephanie Yager, PharmD, and Marigel Constantiner, RPh, MSc, BCPS, CGP, CPh
In the U.S., there are five FDA-approved medications that treat the symptoms of Alzheimer disease by temporarily helping cognition (donepezil, galantamine, rivastigmine, memantine and donepezil/memantine combination). There are new drugs in development that aim to modify the disease process.
Solanezumab is a monoclonal antibody designed to lower the level of beta-amyloid in the brain. Beta-amyloid plaques are found at higher levels in the brains of people with Alzheimer disease. This antibody prevents the formation of plaques and may also help carry beta-amyloid away from the brain. Solanezumab is administered as an intravenous infusion every four weeks. Two phase 3 clinical trials of solanezumab failed to show improvement in cognition or functional ability in patients with mild-to-moderate Alzheimer disease after 18 months. However, a subgroup analysis of patients with mild AD had less cognitive and functional decline when treated with solanezumab. A third clinical trial is underway.
Aducanumab is also a monoclonal antibody that targets aggregated forms of beta-amyloid. Phase 1 trials showed it eliminated large portions of plaques in the brains of people with Alzheimer disease. People on the medication also had a slower decline on cognitive tests, hinting at a functional benefit, although the published trial was too small to prove cognitive effects. Two phase 3 studies are currently underway.
Verubecestat is a beta-secretase (BACE) inhibitor designed to prevent the BACE enzyme from making beta-amyloid. It is administered orally once daily. The study of verubecestat for treatment of mild to moderate Alzheimer’s was stopped due to lack of efficacy. A trial studying this medication in people with prodromal Alzheimer’s is still underway.
Intepirdine is a 5HT6 receptor antagonist designed to increase levels of acetylcholine by blocking the receptor’s ability to decrease acetylcholine. It is administered as a once daily oral medication. A phase 3 trial is expected to be completed in October 2017.
There are 189 additional drugs being tested to treat Alzheimer disease, and more clinical trials on cognitive impairment can be found on the National Institute on Aging website.
Overall, there are exciting new trials studying medications with unique mechanisms to combat Alzheimer disease. Unfortunately, there are no new medications at this time showing substantial clinical benefit.
Stephanie Yager, PharmD, is an ambulatory care pharmacy resident at Cleveland Clinic’s main campus.
Marigel Constantiner, RPh, MSc, BCPS, CGP, CPh, is specialized as a drug information pharmacist and preceptor at Cleveland Clinic with a special interest in geriatrics. She can be reached at constam@ccf.org or 216.444.1126.
References
1. N Engl J Med. 2014 Jan 23;370(4):311-21.
2. Nature. 2016 Sep 1;537(7618):50-6.
3. Alzheimers Dement. 2016 Feb;12(2):110-20.
4. “Merck announces EPOCH study of verubecestat for the treatment of people with mild to moderate Alzheimer’s disease to stop for lack of efficacy” (Press release). Merck. 14 February 2017.
5. Study Evaluating Intepirdine (RVT-101) in Subjects With Mild to Moderate Alzheimer’s Disease on Donepezil: MINDSET Study
6. http://www.alzforum.org/therapeutics/search?fda_statuses=&target_types=&therapy_types=&conditions%5B%5D=145&keywords-entry=&keywords=#results
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