An Alzheimer's Disease Research Center
This past Wednesday, the Penn Memory Center held a community event for PMC patients and families led by co-directors Drs. Jason Karlawish and David Wolk to discuss the Food and Drug Administration’s (FDA) decision to approve Aduhelm (aducanumab). The focus was the impact of the approval on the PMC’s clinical and research operations.
By Dr. Patrizia Cavazzoni, Director, FDA Center for Drug Evaluation and Research
Today FDA approved Aduhelm (aducanumab) to treat patients with Alzheimer’s disease using the Accelerated Approval pathway, under which the FDA approves a drug for a serious or life-threatening illness that may provide meaningful therapeutic benefit over existing treatments when the drug is shown to have an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients and there remains some uncertainty about the drug’s clinical benefit.
This approval is significant in many ways. Aduhelm is the first novel therapy approved for Alzheimer’s disease since 2003. Perhaps more significantly, Aduhelm is the first treatment directed at the underlying pathophysiology of Alzheimer’s disease, the presence of amyloid beta plaques in the brain. The clinical trials for Aduhelm were the first to show that a reduction in these plaques—a hallmark finding in the brain of patients with Alzheimer’s—is expected to lead to a reduction in the clinical decline of this devastating form of dementia.
We are well-aware of the attention surrounding this approval. We understand that Aduhelm has garnered the attention of the press, the Alzheimer’s patient community, our elected officials, and other interested stakeholders. With a treatment for a serious, life-threatening disease in the balance, it makes sense that so many people were following the outcome of this review. Further, the data included in the applicant’s submission were highly complex and left residual uncertainties regarding clinical benefit. There has been considerable public debate on whether Aduhelm should be approved. As is often the case when it comes to interpreting scientific data, the expert community has offered differing perspectives.
At the end of the day, we followed our usual course of action when making regulatory decisions in situations where the data are not straightforward. We examined the clinical trial findings with a fine-tooth comb, we solicited input from the Peripheral and Central Nervous System Drugs Advisory Committee, we listened to the perspectives of the patient community, and we reviewed all relevant data. We ultimately decided to use the Accelerated Approval pathway—a pathway intended to provide earlier access to potentially valuable therapies for patients with serious diseases where there is an unmet need, and where there is an expectation of clinical benefit despite some residual uncertainty regarding that benefit. In determining that the application met the requirements for Accelerated Approval, the Agency concluded that the benefits of Aduhelm for patients with Alzheimer’s disease outweighed the risks of the therapy.
Click the headline or the button below to read this announcement on the FDA website.
Amyloid plaque in the brain. Photo: Adobe
In a recent essay published in STAT News, PMC co-director Dr. Jason Karlawish argued that, given aducanumab’s “incomplete and contradictory” data and the results of an analysis of aducanumab’s effectiveness and value by the Institute for Clinical and Economic Review, the FDA should not approve the drug at this time and stated he will not prescribe it to his patients.
Click the headline or the button below to read this article on STAT News.
Roy H. Hamilton, MD, MS, FAAN, associate professor of neurology and assistant dean for cultural affairs and diversity at University of Pennsylvania’s Perelman School of Medicine, said neurology training would be lacking without an emphasis on racial disparities, especially since many neurologic conditions are more prevalent in minority communities. The neurology department at UPenn began to focus on diversity and inclusion in its training program in 2017, but the initiative is now seen as the core of everything the department does, from hiring to promoting staff to training students and residents.
Dr. Hamilton sees patients in the Penn Memory Center clinic.
Click the headline or the button below to read this article on Neurology Today.
Click the headline or the button below to read this article on PhillyMag.com.
As part of its LiveTalk series, Being Patient spoke with Dr. Jason Karlawish, co-director of the Penn Memory Center and author of “The Problem of Alzheimer’s,” about the advances in dementia research and diagnostics that have allowed for the early detection of Alzheimer’s. Click the headline or the button below to read this article on BeingPatient.com.
By Varshini Chellapilla
If you tested positive for a biomarker of Alzheimer’s disease, whom would you tell? Why?
Penn Program on Precision Medicine for the Brain (P3MB) researcher Emily Largent, PhD, JD, RN, conducted two qualitative studies to understand individuals’ decision-making process as they choose whom, why and how to share information regarding their Alzheimer’s disease biomarker and genetic testing results. The study, titled “‘That would be dreadful’: The ethical, legal, and social challenges of sharing your Alzheimer’s disease biomarker and genetic testing results with others,” was published in the Journal of Law and the Biosciences on May 19.
The studies were done in collaboration with three other researchers from Penn Program on Precision Medicine for the Brain (P3MB): Shana Stites, PsyD, MS, MA; Kristin Harkins, MPH; and Jason Karlawish, MD.
By Varshini Chellapilla
Dr. David Wolk and Grace Stockbower
Clinical Research Project Manager Grace Stockbower, MPH, is moving on from the Penn Memory Center after eight years.
Stockbower came to the center as a research specialist in 2013, after studying psychology and neuroscience at Haverford College. She worked exclusively on studies led by Dave Wolk, MD, PMC co-director.
“We are extremely lucky that we had an opportunity to work with Grace over these last 8 years,” said Dr. Wolk. “She has played a tremendous role in the culture and operation of the Penn Memory Center and our research studies.
Graphic illustration of a T2-weighted MRI with MTL subregion segmentation.
Specialized high-field MRI scanners are some of the most advanced machines in medical research currently and have been equipped to study epilepsy, neurological disorders, and Alzheimer’s disease across many research fields. At Penn, the ultra-high-definition resolution of these MRIs helped researchers study the patterns of atrophy, or loss in volume due to degeneration of cells, in patients with semantic variant primary progressive aphasia (svPPA).
“Volume loss in this region of the brain has been investigated in the past but never with scans as good as these,” said Laura Wisse, PhD, the principal investigator for the study. “With higher resolutions, we were able to measure this particular region of the brain in a much more detailed way.”