Written By: Zemen Habtemariam and Kenneth Dandurand
Edited By: Zemen Habtemariam and Kenneth Dandurand
Aduhelm® (adacanumab avwa, Biogen), was recently approved by the FDA to treat Alzheimer’s disease through the FDA’s accelerated approval pathway. In addition, a label change was announced to limit treatment exclusively to patients with mild Alzheimer’s disease, the patient population that was tested in the trials1.
The accelerated approval pathway is used to grant approval for drugs meant to treat a serious condition that help address an unmet medical need. These drugs are then reviewed for approval based on a specific biomarker, or biological indicator of disease2. In Aduhelm®’s case, the biomarker is the reduction of clustering, sticky plaque in the brain known as amyloid beta plaque.
Aduhelm® is the first FDA approved drug to treat Alzheimer’s disease since 2003. Although we currently have several medications used to treat Alzheimer’s disease such as donepezil (Aricept), memantine (Namenda) and rivastigmine patch (Exelon), these medications are intended only to help with managing symptoms related to Alzheimer’s disease. In turn, they do not assist with slowing down the progression of the disease. Supporters of Adulhelm® believe the drug has the potential, through reducing amyloid beta plaque, to help slow down the progression, which can offer a significant advantage to Alzheimer’s patients and their caregivers.
However, the decision to approve the drug was not a consensus among everyone in the medical community. An FDA Advisory Committee commissioned to review Aduhelm® in November 2020 recommended against approving the drug. Their reasoning? The studies did not provide enough evidence of effectively treating Alzheimer’s disease3. Clinical trials showed mixed results in slowing down the disease, , nor did they show that it actually helped with significantly improving memory or thinking abilities4. In addition, the drug also had an increased risk of significant side effects, such as brain bleeds (a side effect seen in over a third of clinical trial patients), and amyloid-related imaging abnormalities (ARIA), a form of temporary brain swelling that can cause symptoms in patients that include headaches, confusion, dizziness, vision changes, etc. It comes as no surprise, then, that patients screened for Ad helm® eligibility are required to have an MRI scan with four microbleeds or less Prior to use, patients should have definitive brain tests for the amyloid plaque as approximately 30% of patients without amyloid plaques are clinically misdiagnosed with Alzheimer’s and not benefit from treatment with Adulhelm®
Following this accelerated approval, Aduhelm® will undergo additional clinical studies to further examine whether it can significantly slow down disease progression. These studies are known as Phase 4 confirmatory trials, and they are a contingent part of the approval program2. Aduhelm® must undergo these additional trials and pass an additional review to receive full traditional FDA approval to remain on the market.
In addition, the drug’s approval raises financial concerns. Aduhelm®, a weight-based infusion administered once every four weeks, can cost an average weight patient $56,000 a year. Information is still pending on whether CMS programs such as Medicare and Medicaid will be willing to provide coverage, while several national insurers have declined to cover it. Furthermore, several major healthcare institutions such as the Cleveland Clinic and Mass General Brigham announced they would not provide Aduhelm as treatment at this time5. All of these factors impact a patient’s ability to access the drug.
Inquiries and concerns aside, the approval of Aduhelm® could not have come at a more significant time. Alzheimer’s is a highly prevalent disease, affecting an estimated 6 million Americans. In addition to being the sixth leading cause of death in the United States, it is also the third leading cause among older adults. This happens to be the group most affected by the disease, since most patients with dementia caused by Alzheimer’s have late-onset, which occurs after the age of 65.6
The disease also raises concerns not only among its patients, but to their families as well. While there is no confirmed gene for late-onset Alzheimer’s, studies observed a genetic variant of the APOE gene, APOE ɛ4, may be associated with an increased risk for developing Alzheimer’s.6
While the news of Aduhelm®’s approval may bring both advantages and disadvantages, it can be a positive step forward in further advancing treatment and care for a disease significantly impacting the American landscape.
References:
“As FDA Narrows Use of New Alzheimer’s Drug, Providers Proceed With Caution.” Claire Wolters. VeryWellHealth, July 9, 2021, https://www.verywellhealth.com/fda-narrows-use-alzheimers-drug-aduhelm-5192029
FDA Grants Accelerated Approval for Alzheimer’s Drug. Jun 7, 2021. News Release. Available from: https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-alzheimers-drug
“FDA Adviser Who Stepped down over Alzheimer's Drug Approval Says There's No ‘Good Evidence That It Works.’” CBS News, CBS Interactive, 21 June 2021, www.cbsnews.com/news/fda-adviser-alzheimers-drug-aduhelm/.
Full Prescribing Information. Aduhelm [Package insert]. Biogen. 2021. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761178s000lbl.pdf
“Major health centers, insurers push back against Ad helm.” Jacob Bell. BioPharma Dive, 15 July 2021, https://www.biopharmadive.com/news/biogen-aduhelm-cleveland-clinic-sinai-insurers/603392/
“Alzheimer's Disease Fact Sheet.” National Institute on Aging, National Institute on Aging, U.S. Department of Health and Human Services, 8 July 2021, www.nia.nih.gov/health/alzheimers-disease-fact-sheet.
About the Author
Kenneth Dandurand, RPh, MS
Co-Founder and CEO of Clinical Pharmacy Associates, Inc. and Co-Founder and President of MedNovations, Inc. Board Member Asperger/Autism Network
Ken is an ASHP residency trained clinical pharmacist with a BS from Northeastern University and a Master’s from Oregon State University. As an entrepreneur and researcher for 35 years he co-founded Clinical Pharmacy Associates and MedNovations successful leaders in providing direct pharmaceutical care via tele-pharmacy. He is dedicated to improving the delivery of medication therapy management to consumers. To that end, Ken has authored a chapter in the Book “Misadventures in Health Care: Inside Stories” titled “Prescription for Error.”
Zemen Habtemariam, PharmD, is a Pharmacy Practice Fellow for Clinical Pharmacy Associates.
Dr. Zemen Habtemariam, PharmD, is a Pharmacy Practice Fellow for Clinical Pharmacy Associates. He received his B.S. in Chemistry from University of Maryland, College Park and received his Doctor of Pharmacy degree from the University of Maryland School of Pharmacy. He serves as the Pharmacy Practice Research Fellow for Clinical Pharmacy Associates, Inc. He has had broad range of pharmacist experience in community, managed care, and clinical trial settings. He has previously served as the Pharmacist of Record on multiple investigational drug trials. He also assisted in coordinating transitions of care for atypical antipsychotic patients for the Maryland Medicaid Peer Review Program, and conducted comprehensive medication reviews for Spanish-speaking patients for AdhereHealth