These news stories dominated the conversations in the field and were often included in NeurologyLive®'s coverage in Alzheimer disease and dementia.
The world of medical and clinical news was alive with updates on the development of new agents, FDA decisions on promising therapies, and research into better understanding disease pathology and patient care in 2021. As these news stories broke, the NeurologyLive® team was working tirelessly to provide succinct coverage of the through lines by offering the latest information on announcements and insights from experts in patient care and from the industry to keep the clinical community up to date.
In Alzheimer disease (AD), there have been a number of ongoing conversations and interesting debates around therapeutics and clinical care, with the first approval since 2003, a possible improved understanding of the pathology of disease, and a number of successes in the pipeline coming together for a landmark year for the field.
To offer a look back on some of those stories—many of which are still continuing and will extend into 2022—take a look at some of the coverage provided by the NeurologyLive® team that was among the most-read this year. These stories just scratch the surface of our coverage in AD. You can read more news in Alzheimer and dementia, hear experts share insight on the top conversations in the field, and learn more about the ongoing discussions on our Dementia and Alzheimer Disease clinical focus page.
Click the buttons below to learn more about each story.
In June, the FDA approved Biogen and Eisai’s aducanumab (Aduhelm) for the treatment of individuals with Alzheimer disease (AD).1 It was the first approval in the space since 2003 and marked a major point in the ongoing discussion about the controversial therapy—much of which has continued to this very day. With a pending coverage decision from the Centers for Medicaid and Medicare Services still coming in the next few months, these conversations are not likely to end soon, particularly amid the news in recent days that Biogen would be cutting the price of the drug by 50%.
At the time of its approval Patrizia Cavazzoni, MD, director, FDA Center for Drug Evaluation and Research, said in an agency statement that "This approval is significant in many ways. Aduhelm is the first novel therapy approved for Alzheimer disease since 2003. Perhaps more significantly, Aduhelm is the first treatment directed at the underlying pathophysiology of Alzheimer 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—is expected to lead to a reduction in the clinical decline of this devastating form of dementia."
Additionally, trial investigator Marwan Sabbagh, MD, director, Cleveland Clinic Lou Ruvo Center for Brain Health, told NeurologyLive® at the time that "this is a seminal moment in the field. I was surprised at how polarizing it was—we really had strong opinions for and against—but if you take the pro-patient aspect, and look at this in the context of the fact that many drugs are starting to show similar signals, I think this is a great step forward. People have to understand that contextually, medically speaking, we need the first drug in the class to get the class going forward. Otherwise, there's going to be no progress."
In January, Eli Lilly announced results from its randomized, placebo-controlled, double-blind, multi-center phase 2 TRAILBLAZER-ALZ study (NCT03367403) investigating donanemab for slowing the progression of Alzheimer disease.2 When compared with placebo, patients treated with donanemab showed a significantly slower decline in cognition and daily function—those treated with donanemab declined 32% slower compared to placebo as assessed by the Integrated Alzheimer's Disease Rating Scale (iADRS) from baseline to 76 weeks. Donanemab also showed consistent improvements in secondary end points measuring cognition and function as compared to placebo, but not all of these endpoints reached statistical significance.
Donanemab continued through the pipeline throughout 2021, with the company announcing in June 2021 that the FDA had granted breakthrough therapy designation for donanemab, along with plans to submit a BLA for the therapy—a process it initiated in rolling fashion in late October based on data from the phase 2 TRAILBLAZER-ALZ study. Additionally, in October, the company announced plans to conduct TRAILBLAZER-ALZ 4, a phase 3 head-to-head trial comparing donanemab to aducanumab (Aduhelm; Biogen), the most recently approved disease-modifying therapy (DMT) for patients with early AD.
At the time of the original data announcement, Daniel Skovronsky, MD, PhD, chief scientific officer, and president, Lilly Research Laboratories, Eli Lilly, expressed his confidence in the results in a statement from the company. "This is the first late-stage study in Alzheimer's disease to meet its primary endpoint at the primary analysis. Donanemab has the potential to become a very important treatment for Alzheimer's disease. We were pleased to see not only slowing of cognitive and functional decline, but also very substantial clearance of amyloid plaques and slowing of spread of tau pathology," he said.
In February, Cassava Sciences announced that simufilam, its investigational, oral, small molecule treatment for AD, had shown to be associated with the improvement of cognition and behavior in individuals with AD without any reported safety issues in the results of an open-label study. Additionally, it announced that the FDA had concluded a successful end-of-phase 2 meeting for the drug’s development program, the enrollment target for which is planned to be increased by up to 50 additional patients, for a total target of approximately 150 patients.3
The company noted that these findings and noted that in combination with prior clinical trial results, it supports the advancement of simufilam into a phase 3 clinical program in AD, announcing the initiation of a pair of phase 3 trials in October and November, respectively, called RETHINK-ALZ (NCT04994483) and REFOCUS-ALZ (NCT05026177).
Although, earlier in the year, in late August, Cassava Sciences was accused of scientific misconduct and fraud in complaints filed in an FDA citizen petition by Labaton Sucharow, a shareholders’ rights law firm. These complaints called the validity of the simufilam data into question, and though Cassava Sciences has responded, experts in scientific misconduct have continued to debate the story. In November, Cassava noted that “certain government agencies” had inquired with the company to acquire “corporate information and documents” and that it is cooperating with these requests, and that to this point, “No government agency has informed us that any wrongdoing has occurred by any party.”