Phil Gutis, a career reporter and writer living with early-onset Alzheimer's, participated in the clinical trials for the first-ever disease-modifying Alzheimer's drug. Now, he reflects on the approval of the second: lecanemab, brand name Leqembi, approved by the FDA on January 6, 2023.
I received my diagnosis of early Alzheimer’s in July 2016 through participation in a clinical trial for Biogen’s aducanumab (now known as Aduhelm). Except for a year-long pause when Biogen withdrew the drug because of a flawed scientific analysis, I’ve watched the aducanumab rollercoaster with more interest than most and cheered when the FDA approved aducanumab (under the brand name Aduhelm) as the first-ever disease-modifying treatment for Alzheimer’s. I hoped that it would soon be widely available and would be able to help others as I firmly believe it has helped me.
Of course that was not to be, as the Centers for Medicare and Medicaid Services took the extraordinary step of blocking widespread Medicare coverage of Aduhelm. The CMS said they weren’t persuaded of the effectiveness of aducanumab despite the FDA’s decision that aducanumab addressed “an unmet medical need in treatment of a serious or life-threatening condition.”
Experts said the CMS decision was unprecedented and blocked access to breakthrough treatments in ways that other treatments for other diseases have not experienced. In other words, Alzheimer’s was being treated differently than cancer, than heart conditions, then AIDS.
Today, the FDA granted approval of lecanemab, making it the second-ever disease modifying drug. It will be distributed under the brand name Leqembi.
As expected, there were a flurry of congratulatory press releases from advocacy organizations – including the two I’m most closely associated with, the Alzheimer’s Association and Voices of Alzheimers. As expected, each of the organizations that praised the FDA and urged the CMS to rethink its discriminatory decision to block widespread coverage of the “-mabs,” the class of monoclonal antibody drugs that includes aducanumab and lecanemab.
But really, what has changed? We’ve heard potentially hopeful words from Chiquita Brooks-Lasure, the CMS administrator, who said in December that her agency is prepared to reconsider its decision.
“I can’t speak to any specifics, but just to say that our door is really open,” Brooks-LaSure said. “We will look at it as new data comes.”
Let’s hope we can take the administrator at her word and that there is really a serious reconsideration underway at CMS. Unfortunately, there are historical reasons to be skeptical as Medicare has a history of making misleading statements to keep critics at bay.
Another good sign is that some researchers and clinicians have already reconsidered. Way back in September, when the first round of data from the new drug Lecanemab was released by drugmakers Eisai and Biogen, I noted that Dr. Jason Karlawish of the University of Pennsylvania had changed his tune.
Will Leqembi make a meaningful difference for people living with Alzheimer’s?
Back in 2021, as the FDA considered aducanumab, which became the first-ever approved disease modifying drug for Alzheimer’s, Karlawish gained quite a bit of notice for his opposition to the drug. If the FDA gave aducanumab “the green light,” Karlawish wrote, “I can’t see myself recommending it to my patients.” His biggest concern, he said, was the messy nature of the clinical trial and the resulting data.
With Leqembi (lecanemab), Karlawish shifted: “If what they report is all proper and true and valid and holds up to scrutiny, we have an effective treatment for Alzheimer’s disease,” Karlawish told the online news site Axios.
I’d been exchanging messages with Karlawish for months about his opposition to aducanumab. (Full disclosure: I continue to receive aducanumab as part of an ongoing clinical trial into its efficiency, and for several years, I participated in the trial at the University of Pennsylvania’s Memory Center, which Karlawish co-directs.)
When I saw Karlawish’s positive comments about lecanemab, I wrote to him again.
“Can you please explain in non-science speak the difference between the data we saw in Aduhelm and what we saw with lecanemab?” I asked. “From what I understand, we’ve seen 22 percent effectiveness versus 25 percent effectiveness in slowing.”
“I know the Aduhelm data was messy,” I continued, “but from a straightforward 22 versus 25 delay in progression, how is a layperson to understand the difference?”
His response: “The problem with the aducanumab data are the quality of the data. It simply was not up to par. Never mind the 22 percent figure.”
I followed up. “So to put a fine point on it, if the Aduhelm data had been clean, the 22 percent would have been considered a success?”
“It would have been considered a drug effect greater than chance,” he responded.
Translating Alzheimer’s drug science for the people it matters to most
So what does effectiveness mean? Here’s where we get into the land of almost incomprehensible statistics. I’ll return to my story way back in 2019 when aducanumab data was first presented at a scientific conference in San Diego: “The scientific data was virtually unreadable, the explanations often too complex for the layman or woman to understand.”
Not much has changed. The data is still awash in terms like p-factors and other statistical terms. But the lecanemab study did look at a scale that is based on activities of daily living, activities such as finding belongings, selecting clothing, getting dressed, cleaning the house, balancing a checkbook, writing notes, doing laundry.
Other activities that were looked at are keeping appointments, using a telephone, making a meal, traveling outside the home, talking about current events, reading, watching television, shopping, being left alone at home, using household appliances, driving, taking medications and initiating complex activities.
During the lecanemab trials, caregivers were repeatedly asked to evaluate the performance of participants. The scoring range was zero to 53, with higher scores better. The bottom line was that participants on Lecanemab (versus those who received a placebo) showed significantly less decline in performing those activities.
Various groups are looking into the question of meaningfulness. UsAgainstAlzheimer’s is planning a webinar on the topic soon. And the Alzheimer’s Association has put together a working group on the question of meaningfulness.
Maria Carillo, the Association’s chief science officer, offered this explanation: “The workgroup will develop materials and activities to advance the conversation on the slowing of disease progression and its relationship to clinical meaningfulness among researchers, clinicians, affected individuals and families.”
The meaningfulness conversation is critical. Without it, we’re left swimming in a sea of statistics that mean absolutely nothing to the people living with this disease. In the months leading up to a CMS decision on lecanemab, I’m hopeful that those of us living with the disease can raise our voices so policymakers at CMS and throughout the government understand how important it is that we retain our basic humanity for as long as possible.
Phil Gutis is a former New York Times reporter and current Being Patient contributor who was diagnosed with early onset Alzheimer’s. This article is part of his Phil’s Journal series, chronicling his experience living with Alzheimer’s and his participation in the aducanumab clinical trial.