If you haven’t already heard, the FDA announced that it has approved a new drug, Adulhelm, developed by pharma-giant Biogen, for the treatment of Alzheimer’s Disease on June 7. Adulhelm is the brand name for of generic drug name aducanumab.
The bad news? For starters, the drug hasn’t been shown to significantly improve or delay symptoms of the disease. One of two clinical trials showed that using the high dose of the medication slowed cognitive decline only slightly — by about four months in an 18-month period or by an improvement of .39 of an 18-point cognitive test. A subsequent identical study showed no significant clinical effect compared to placebo. While the drug is “intended” to impede disease progression, there’s no hard evidence that this will happen.
The approval has been accompanied by heavy controversy, including the voices of the FDA’s independent advisory committee involved in this trial. In fact, as of this writing, three members of said committee have resigned in protest over the decision to approve the use for a broader than intended population. By the way, the FDA was not acting here as a tiebreaker: 10 of 11 advisers voted to reject Biogen’s application and the 11th was undecided on how to interpret the data.
Then There’s the Cost
Biogen has established the list price of the drug, which must be administered intravenously once a month, at $56,000 a year. That’s just for the price of the drug. And while an insurer (namely Medicare) will likely cover some of that cost, those who receive this drug treatment will be required to have PET scans to detect amyloid clumps, deemed crucial to diagnosing Alzheimers. Pet scans can cost thousands of dollars and are not covered by Medicare. Nor are the multiple follow-up scans needed to check for tiny brain bleeds (microhemorrhages) or brain swelling which are potential side effects of the drug. In fact, during the clinical trials, some 40 percent of participants given the highest dose had one or both of these side effects.
We’ve Been Down this Road Before…. Many Times
But never mind the cost and the ambiguous “hope this helps” claim that the drug manufacturer holds out like a carrot on a stick. The rationale, according to the FDA for its approval of Aduhelm, is that reducing amyloid, the sticky stuff responsible for brain plaque, could be reasonably expected to benefit brain function.
But this is the same thinking that drove Pfizer’s development of a similar anti-amyloid antibody drug called bapineuzumab, over ten years ago. Those trials were reported in The Lancet Neurology in 2010. Pfizer ultimately abandoned bapineuzumab because, although amyloid accumulation was reduced over the course of the trials, there was no meaningful impact on clinical outcome.
Since then, the failure of amyloid reduction in a decade of drug failures like bapineuzumab, solanezumab, (I know, they all have long, funny names) and others, the absence of clinical benefit by solely attacking amyloid brain plaque has been noted by many experts.
Should Aduhelm Be Available for All Stages of Alzheimer’s?
With luck and a prayer and a shred of evidence, the drug’s proponents suggest that it’s possible that when mildly impaired patients are treated for five years or 10 years or more with Aduhelm, there will be an obvious benefit. Fingers crossed that this is the case.
But the FDA’s surprise approval included the decision to use a broad label for the treatment. That means that any of the more than 6 million people in the U.S. with Alzheimer’s would be eligible, not just those in very early stages. Will it be the physicians’ and insurers’ call as to who will be treated? That’s a tough job to face without guidance from the manufacturer.
What Will Happen if the Confirmatory Trial Fails?
As I write this, the news headlines tell me that the drug is now being readied for shipment and administration within two weeks. Patients and their families are already scrambling to get their place in line for the new drug.
But there’s another caveat. The FDA’s approval is conditional – Biogen must conduct one other massive scientific trial to validate the outcomes generated in a subset of sufferers in solely one in every of its two scientific trials. That’s called a confirmatory study, one that confirms how well a new treatment works after it was shown in early-phase clinical trials that it might be beneficial for patients.
I’m not surprised to learn that Biogen does not expect to start a multiyear study until 2022. The proposed study design is long and time-consuming, effectively giving Biogen nine years' time to market the drug without fear of repercussions. If the trial fails, then the company gets to keep its earnings from the drug -- with no refunds.
The Cruelty of False Hope
I winced when reading the headline from the Alzheimer’s Association website on June 7: “It’s a New Day in the Fight Against Alzheimer’s — Aducanumab Approved”. To give them a fair shot, I listened in on a live broadcast sponsored by the Association on June 24. In the broadcast, physician Stephan Solloway explained basic differences between Adulhelm and drugs that are currently available for Alzheimer’s Disease and emphasized that the drug should only be used for those with mild cognitive impairment, not in advanced stages of the disease. Agree.
But I didn’t hear anything about how significant the clinical benefit was when measured in the one trial that showed improvement nor how this drug is different from previously developed – and abandoned – amyloid antibody treatments that have failed so many times before. I asked both of these questions in the short Q&A time, but neither was addressed.
I hope I’m dead wrong and that the treatment will mean better quality of life for those it helps. I hope it works in spades for the patients who choose to jump on board in desperation and in gratitude for the research scientists who work at Biogen and a forward-thinking FDA. Yet behind that hope is a sinking feeing in my gut that questions how this will be different from so many other attempts to fix Alzheimer’s by removing its hardware. Time will tell.