This past Monday, June 7, 2021, the Food and Drug Administration (FDA) approved the first new Alzheimer’s drug in nearly two decades. The drug, Aduhelm is manufactured by Biogen, Inc. and its action is to reduce the sticky protein substance in the brain called amyloid, which is associated with the cognitive decline in Alzheimer’s disease. This drug offers hope to millions of people affected by this dreaded disease and to their caregivers as well. According to the Alzheimer’s Association, more than 6 million Americans are living with Alzheimer’s and by 2050 this number is projected to rise to nearly 13 million people.
What You Need To Know
The decision by the FDA to give accelerated approval to this drug has been met with controversy since the drug demonstrated limited treatment outcomes for patients in studies. For this reason, the FDA has advised Biogen to conduct a post-approval study to confirm the drug’s benefit. If the new trial, called a Phase 4 trial, fails to show the drug is effective, the FDA can rescind its approval. The current medications offered for the management of Alzheimer’s patients are given in pill form, this drug is different and administered via an infusion given monthly. Costs affiliated with the use of the drug are estimated to be over $50,000 per year and use will include diagnostic tests and imaging. The costs for patients will vary on what their insurance plan will pay. Medicare is expected to cover the treatment and private insurance will cover what is deemed medically necessary by the doctors. Insurers will likely request documentation first from physicians citing that the drug is indicated for their condition.
How does Aduhelm work in the brain?
Aduhelm is a lab-made antibody that protects the body from harmful substances, such as toxins and viruses. When infused into the body, the Aduhelm antibodies attach onto amyloid clusters in the brain and remove them. It is the drug’s ability to remove the amyloid plaques that will lessen cognitive decline. The drug will be targeted at patients with mild memory and thinking problems. It is the first approved treatment for Alzheimer’s that attacks the disease process and not the dementia symptoms. Patients treated with Aduhelm will require monitoring with MRI imaging tests to monitor for small brain bleeds, a possible side effect of the drug. In clinical trials, 41% of Aduhelm treated patients had side effects detected on MRI, which included brain hemorrhage or an accumulation of fluid in the brain.
What is the debate about Aduhelm’s performance and use?
Aduhelm’s history of development has had many twists starting in March of 2019 where two late-stage studies were terminated. Following an analysis of the data, it was determined that there was a less than 20% chance that the drug would succeed in slowing study patients’ cognitive decline. Later in 2019, Biogen cited that one study was successful and one was not due to a study design change in the middle of the trial.
The FDA Advisory Board and a panel of independent experts raised the question that the drug was not very effective in clinical trials. Some of the clinicians also cited that the risk of using the drug, which included brain swelling and bleeding and the high cost did not add up to the slight benefits of the drug. In response to these concerns, Dr. Patrizia Cavazzoni, the FDA’s director of the Center for Drug Evaluation and Research, stated that the drug was given approval through the agency program call “accelerated approval”. This program is designed to allow access to potentially valuable therapies for serious diseases when there is an unmet need despite some uncertainties about the treatment.
Who should be treated with Aduhelm?
Clinician feedback to the use of Aduhelm has included that the drug label cited by the FDA touts that Aduhelm can be used by a larger range of patients, at any level of Alzheimer’s disease with any symptoms. This is different than the population that participated in the clinical trials. Most of the participants were in the earliest stages of Alzheimer’s disease, with mild symptoms.
One of the principal investigators of the clinical trials, Dr. Stephen Salloway, the director of the Butler Hospital’s Memory and Aging Program, was hoping with the approval would come more narrow guidance on the population of use. He stated that there is really no evidence that it works on late-stage Alzheimer’s disease. He went on to explain that the amyloid process, which the drug targets, peaks during the early stages of the disease. Many neurologists are concerned that doctors with the power to prescribe the drug will be asked to prescribe it even when not indicated and they may not have the expertise in Alzheimer’s disease. Hopefully, industry gatekeepers will keep the use of this new drug in the appropriate population.
References:
https://www.wsj.com/articles/first-alzheimers-drug-to-slow-disease-is-approved-by-fda-11623078912
https://www.alz.org/alzheimers-dementia/facts-figures
https://www.fda.gov/drugs/information-health-care-professionals-drugs/accelerated-approval-program