The first UCHealth patient has received an infusion of the first drug approved by the FDA to slow the progression of Alzheimer’s disease.
The generic name for the drug is lecanemab and the brand name is Leqembi.
Greg Young, a 78-year-old from Larkspur, became the first UCHealth patient to receive Leqembi with his initial infusion on June 26.
Greg and his wife, Patty, first bonded over their shared love of horses when they met 15 years ago and married a couple of years later. About six or seven years ago, Greg began noticing increased forgetfulness. His symptoms then worsened during the COVID-19 pandemic.
“After getting (COVID), his memory was not as sharp,” Patty said. A standout incident occurred in the kitchen as they cooked together, which they like to do.
“He forgot how to make a lemon-butter sauce for artichokes that we always have,” Patty said. “He was the one who taught me how to make it.”
Patty also began noticing that Greg couldn’t remember where plates and utensils went when he unloaded the dishwasher and at times, had trouble focusing on a task at hand.
Greg eventually received an Alzheimer’s diagnosis. Through his doctors, he soon learned about Leqembi and became the first patient to qualify for the new treatment.
Greg and Patty know that Leqembi is not a cure for Alzheimer’s, and doctors, patients and researchers still have much to learn about its effectiveness. Still, the Youngs felt it was worth trying.
“We’d rather try to do something,” Greg said. “If we have good results, it helps the [Neurology] program, and it helps us. I hope it helps me feel fresher and keeps me steady.”
Setting up a safe system to provide Leqembi to patients who qualify
While Leqembi received FDA approval last year after a phase 3 clinical trial of nearly 2,000 patients, it has taken several months for UCHealth experts to set up a safe system for patients to be properly screened and to receive the new infusions.
The drug works through infusions that target beta-amyloid, the protein that builds up and creates sticky plaque in the brains of people with Alzheimer’s disease. The trial demonstrated that it reduced cognitive and functional decline in those who took it, compared with a placebo.
The 2023 FDA green light for Leqembi was cause for both celebration and caution at UCHealth. Systems had to be put in place to evaluate patients since the drug is not for everyone. Medical providers also needed to ensure there were adequate numbers of infusion chairs and staff to administer the drug, and develop measures to ensure patient safety.
Dr. Victoria Pelak, professor of Neurology and Ophthalmology at the University of Colorado School of Medicine on the Anschutz Medical Campus, summed up the challenges in an interview shortly after the FDA approval last summer.
“Because of the risk and complexity of the diagnosis and the discussions of the drug’s risks and benefits, we need strong protocols in place, not only for those who are eligible, but also to determine if someone is ineligible,” Pelak said.
Who is eligible for Leqembi, and how do patients get screened?
Medical experts at UCHealth have spent the last year working to ensure that patients who receive Leqembi are those most likely to benefit from it and to minimize its safety risks.
Job one is screening patients, said Dr. Tara Carlisle, a behavioral neurologist and assistant professor of Neurology with the University of Colorado School of Medicine. She sees candidates who wish to receive Leqembi at the University of Colorado clinic for Advanced Therapy for Neurodegenerative Disorder. It’s part of the University of Colorado Neurobehavior and Memory Disorders Clinic at the UCHealth Neurology Clinic – Central Park.
“In order to be eligible for Leqembi, a person needs to have cognitive impairment that is suspected to be due to underlying Alzheimer’s disease,” Carlisle said.
For those patients, clinic staffers then perform tests to confirm that a patient has Alzheimer’s and determine how severe it is.
The process begins with a lumbar puncture to look for evidence of amyloid and tau, which are the two proteins most closely associated with Alzheimer’s disease. Less frequently, providers perform an amyloid PET brain scan to detect signs of the proteins.
Patients who are eligible for Leqembi must have mild cognitive impairment or mild dementia due to Alzheimer’s disease. Those who have advanced to the moderate stage of Alzheimer’s — meaning they need assistance with everyday activities — are not candidates for the drug, Carlisle said.
Patients on drugs that suppress the immune system are excluded because Leqembi works by activating the immune system. Patients who take blood thinners also are not candidates because Leqembi was shown in clinical trials to increase the risk of amyloid-related imaging abnormalities, or ARIAs, including brain swelling and bleeding. Patients get a baseline MRI on specific scanners to look for signs and risks of ARIAs, Carlisle added.
The genetic factor in Leqembi treatment
For those who are still candidates to receive Leqembi, the clinic recommends testing for the APOE4 gene, which is a strong risk factor for Alzheimer’s disease in people with two copies. Carlisle explained that these individuals are doubly disadvantaged. They have a greater risk of brain bleeding and swelling, and a separate analysis from the phase 3 clinical trial of Leqembi showed that they were “unlikely to get actual benefit from the drug,” she said.
“We’re not requiring the genetic test,” Carlisle added. “But as part of the counseling, we explain that there is a different benefit and risk profile, depending on if you have no copies, one copy or two copies of the APOE4 gene.”
For individuals with two copies, Carlisle said the clinic starts a “shared decision-making conversation” and will administer the Leqembi infusions with the understanding that they might need additional monitoring for brain bleeds and swelling.
Space for Leqembi infusions
As of early June, Carlisle said she had evaluated about two dozen patients with Alzheimer’s and was averaging four new patients a week. At that time, two patients had made it to the “final steps” to receive the infusions, which will be administered every two weeks for 18 months in the UCHealth Outpatient Infusion Center on the Anschutz Medical Campus, she said.
Another infusion center in the Neurology Clinic at Central Park has been built, and providers will start scheduling patients soon, Carlisle added.
Safety first for Leqembi infusions
In addition to developing these patient-selection measures and creating the infrastructure for infusions, Carlisle said UCHealth spent considerable time crafting a “robust safety protocol” for patients who choose to receive Leqembi.
“That’s one of the reasons that we’ve taken a little bit longer to get our program up and running,” she said.
As part of that work, Carlisle said she communicated with other centers, such as Brigham and Women’s Hospital, Massachusetts General Hospital and University of California San Francisco Hospital, to learn about their patient safety measures.
To monitor the risk of ARIAs, clinic managers worked closely with University of Colorado School of Medicine neuroradiologists to ensure they have the training to identify brain bleeding and swelling and that they follow American Society of Neuroradiology guidelines for doing so, Carlisle said. The safety details extend to ensuring that a patient’s follow-up brain scans are done on a similar scanner to avoid variations between manufacturers, she added.
Patients will also be closely monitored during and after their infusions, Carlisle said: three hours after the first one and two hours each for the second and third treatments, to guard against “delayed infusion reactions,” such as fever, chills and muscle aches that can be easily treated, or more serious problems. Following these initial infusions, Carlisle said her nurse infusion navigator will follow up with patients later that day to check on how they are doing.
The long view of Leqembi’s effectiveness
For patients and providers, of course, the ultimate question is whether Leqembi actually works. Carlisle said her clinic is doing initial screenings of patients’ thinking, memory and function. They will then follow up at six, 12 and 18 months.
“We are trying to get an idea of their trajectory over time. How are they are doing, has their quality of life improved or worsened? We want to understand the impacts of this drug,” she said.
The testing and treatment time demands for Leqembi infusions are important considerations for patients to take into account, Carlisle said. “You basically become a full-time patient,” she noted.
They met through a love for horses and hope to keep enjoying their passions
Greg and Patty hope that Leqembi infusions will allow them to continue enjoying riding horses, cooking together and enjoying beautiful mountain views from their home south of Denver.
The couple met through a foxhunting group called the Arapahoe Hunt, which is based in Franktown. Greg is a lifelong resident of Douglas County and always has loved riding horses. He enjoyed a career selling and installing windows and doors. Patty, meanwhile, had worked for 42 years as a dental hygienist in the Denver area.
She was busy administering her late brother’s estate a little more than 15 years ago when an attorney assisting her with the work made a suggestion.
“He told me, ‘Patty, you need to get a life,’” she recalls.
The attorney encouraged Patty to join the Arapahoe Hunt, which she’d never heard of, to make some social connections. She gave it a try, met Greg, and began riding with the hounds, which Greg and Patty still do.
Evaluation for Alzheimer’s disease
When Greg started to feel that his memory was slipping, he consulted with his primary care provider in Frisco, who administered some simple memory tests. The tests gave him enough trouble that Greg’s doctor referred him to a neurologist for further evaluation, which indicated he had Alzheimer’s disease. A follow-up test a year later showed his cognition had declined further.
Greg found the news enlightening rather than depressing.
“It explained a few things,” he said. “It was nice to have a diagnosis.”
Greg’s primary care provider told the Youngs about Leqembi, which had recently received FDA approval, and recommended that they contact UCHealth to inquire about receiving it. The Youngs eventually secured an appointment with Dr. Samantha Holden, medical director of the University of Colorado Neurobehavior and Memory Disorders Clinic and an associate professor of Neurology at the University of Colorado School of Medicine. Holden has played a key role in helping UCHealth experts prepare to safely begin administering Leqembi.
As soon as the clinic began screening patients for Leqembi, Greg went through the time-consuming but vital testing regimen that ultimately ended in approval for him to receive Leqembi.
“We don’t mind the time commitment,” Patty said. “If it slows the progression of the disease, that’s what we want.”
The promise and uncertainty of Alzheimer’s disease and treatment
While Greg and Patty still love their shared passions, Patty acknowledges that Alzheimer’s disease already has changed their relationship a bit.
“I am the caregiver and have taken on more responsibility in making decisions and following through with things that need to be done,” she said. “It’s nothing that I can’t handle, but there is anxiety. It is important for me to be patient and kind.”
Whether or not Leqembi gives Greg and Patty a few extra months of quality time together remains to be seen. For her part, Carlisle stresses that the drug’s approval is just one important step in a much longer battle against Alzheimer’s disease.
For example, Leqembi targets only amyloids, which are but “one piece of the pathology” of the disease, Carlisle said. The drug does not affect tau, the cognition-deteriorating tangles in the brain. What happens to cognitive decline and disease progression in patients after 18 months of Leqembi treatment is also an open question.
Still, Leqembi is “the first potentially disease-modifying drug for Alzheimer’s” after years of futile clinical studies, which raises hopes for future breakthroughs, Carlisle said. For example, an FDA advisory panel found in early June that donanemab, another drug that targets beta-amyloid, was effective in slowing cognitive decline in people with mild Alzheimer’s disease. If donanemab gains full FDA approval, patients who receive it would require infusions every four weeks, instead of two.
“What I am most optimistic about is what this means for the future of treating neurodegenerative disorders,” Carlisle concluded.