The Food and Drug Administration’s approval of Biogen’s Alzheimer’s drug Aduhelm has stirred intense controversy, with pundits launching attacks on multiple fronts. Professors focus on population outcomes rather than individual treatment responses; politicians worry about drug pricing rather than disease cost; critics pounce on the FDA’s narrowing of the drug’s label to reflect its clinical trial — all casting doubt on the drug’s effectiveness and value.
What’s been lost in the flurry is an understanding of how progress against complex diseases advances — and the historic importance of Aduhelm as a first step in that process.
Alzheimer’s robs people of memory, cognition, and the dignity of being human. It is a public health crisis that will eventually bankrupt every health care system challenged with financing institutionalized care for the coming wave of dementia patients. There is no cure and no standard therapy. The wasteland of research failures causes many investigators to shy from committing careers to Alzheimer’s, while the biopharmaceutical industry avoids the risk of futile investments of billions of dollars.
This year, for the first time since Alzheimer’s was first described in 1906, the FDA granted what’s called accelerated approval for a drug with substantial evidence of affecting the underlying disease mechanism, though its effects on symptoms remains to be elucidated.
Fifty years ago, when the National Cancer Act was passed, cancer posed much the same threat as Alzheimer’s disease poses today: no cure, only rudimentary understanding of the disease, and an enormous emotional and financial toll on families and society. Yet many forms of cancer are now amenable to cures or long periods of remission and control.
This progress did not take place in one giant leap.
In the earliest days of cancer chemotherapy, a modest response rate of 20% to 30% was celebrated as a victory, especially compared to zero. Those responses mattered because they exposed tumors’ vulnerabilities and offered hope for those who responded to treatment and their loved ones.
As a cancer physician and former director of the National Cancer Institute, I believe the burden should be on critics to explain why we should not view biological responses to Aduhelm in people with Alzheimer’s the same way and follow the same road map to greater success.
Early, tentative responses to new therapies mobilized the cancer community to a sustained effort at building on incremental progress. With patience, persistence, and the heroic participation of cancer patients who braved potential side effects, researchers and clinicians made astounding gains.
In my own experience as a urologic oncologist, the results in widespread metastatic testicular cancer have been stunning. Once a virtual death sentence with no curative treatments, patients now experience an almost 100% survival rate utilizing a combination of chemotherapy agents.
This history of progress in the fight against cancer shows that the FDA was right to approve Aduhelm — not as a silver bullet but as a first, essential step in climbing a mountain to success for people with Alzheimer’s disease and their families.
Obscured by the current angst is that Aduhelm demonstrated a profound effect on amyloid plaques in patients’ brains. A peer-reviewed study offered evidence why Aduhelm may work when previous anti-amyloid therapies failed: Aduhelm appears to interrupt the cascade of damage from toxic molecules becoming plaque — “uniquely” among the antibodies studied, according to the authors.
Researchers will eventually discern whether amyloid plaque is a cause of Alzheimer’s disease or an effect of it. But reduction of plaque is an essential observation — just as in a cancer trial where survival is the meaningful endpoint but tumor response is the critical observation because it shows researchers they are on a path that matters.
The FDA has launched this journey for Alzheimer’s with the accelerated approval of Aduhelm. In fact, the agency has already taken the next step by granting Eli Lilly’s Alzheimer’s treatment, donanemab, breakthrough designation, which is intended for serious or life-threatening conditions in which preliminary clinical evidence supports a potential significant improvement over existing therapies.
The process of incremental innovation will accelerate as evidence of Aduhelm’s biologic effects accumulates. Clinicians who choose to use this drug have a responsibility to collect data and share information with colleagues, the drug sponsor, and the FDA. Oncology was fortunate to have an infrastructure in place, utilizing the NCI Designated Cancer Centers and Cooperative Clinical Trial Groups launched by the National Cancer Act. Today that infrastructure can be virtual. Modern tools of data acquisition, aggregation, and analysis leave no excuse for not assembling a registry of patients and insights into their response to therapy. Biogen should create such a registry to follow every patient who gets Aduhelm. That could significantly accelerate progress against Alzheimer’s disease.
Aduhelm is not a silver bullet in the battle against Alzheimer’s, and the hand-wringing critics are wrong to hold it to that standard. The more productive route is to recognize the drug as a first treatment that can galvanize the scientific/medical community, industry, and patient advocates to begin the hard, step-by-step process that leads to better treatments and hopefully, one day, a cure. That’s the future we all wish for Alzheimer’s and all neurodegenerative diseases. That’s the effort we owe to desperate patients living in fear they will not recognize or remember the names of their loved ones.
Andrew C. von Eschenbach is an oncologist, president of Samaritan Health Initiatives, former director of the National Cancer Institute, former commissioner of the Food and Drug Administration, and a member of the board of Wren Therapeutics. He reports having no financial relationships with Biogen.
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