Alzheimer's drug trialed by Penn Medicine receives FDA approval

The Federal Drug Administration recently approved a drug trialed by the Penn Memory Center to reduce the risk of developing Alzheimer’s disease.

The drug, Leqembi, received FDA approval under the accelerated approval pathway on Jan. 6, after the AHEAD trial assessed its efficacy on volunteers concluded its third phase. Researchers at Penn Medicine have been studying volunteers who do not exhibit extreme dementia symptoms but who may be at risk for future development, as the study aims to preemptively prevent symptoms.

As of September, the AHEAD clinical trial studied nearly 1,800 individuals. These trials have reported a 27% improvement in slowed or reduced cognitive decline compared to those who received a placebo.

David Wolk, the co-director of the Penn Memory Center and the director of the Alzheimer’s Disease Research Center at Penn, wrote in a statement that these results are an “extremely encouraging development.”

Leqembi aims to reduce the damage caused by amyloid proteins, which may be associated with memory and thinking impairment. Amyloid proteins are found in higher quantities in the brains of Alzheimer's patients.

The recent FDA approval did not take into account data and results from phase III trials of Leqembi. There remains concern about the drug's longer-term impacts, as three patients enrolled in the trial have recently died from brain bleeding and swelling complications. Some researchers have claimed these deaths may be linked to the drug.

Sanjeev Vaishnavi, a neurologist at Penn Medicine, told The Daily Pennsylvanian that the drug has the potential to be reproduced naturally in humans.

“[The drug] was derived actually from the blood of individuals who were older who did not develop Alzheimer's disease,” Vaishnavi said. “It’s one of these few things that kind of started from humans, went into the lab, and now it’s back in humans.”

Much of the research conducted with Leqembi to this point has proved that it slows down memory degradation in patients that already have Alzheimer's symptoms. Now, the AHEAD study hopes to slow down the process of acquiring symptoms in the first place, Vaishnavi said. 

Previously, drugs intended to combat memory loss have not had much clinical success. This lack of success has led some doctors to speculate that amyloid proteins are not a cause of Alzheimer's, but rather an incidental side effect.

An alternative explanation provided by some clinicians is that a protein called Tau is the primary culprit of Alzheimer’s Disease. Virginia Man-Yee Lee, director of the Perelman School of Medicine’s Center for Neurodegenerative Disease Research, has led research on Tau.

Overall, Alzheimer's researchers have encountered a multitude of challenges while trying to explore the disease. For instance, Alzheimer's symptoms show and progress over many years, which means that clinical trials must last for long periods of time, Vaishnavi told the DP.

“Speeding things up and identifying the appropriate individuals for research … [is] the work we’re continuing to do moving forward,” Vaishnavi said. “The hope is that if [Leqembi] works for people with more significant memory loss symptoms, it may work even better for people earlier. That's the big-picture thought process.”