Biogen’s Alzheimer’s candidate aducanumab may be a longshot to pass muster with Food and Drug Administration medical reviewers. But should it snare an approval on decision day — slated for next Monday, June 7 — the drug would have a chance to define a category. 

As possibly the first treatment to slow cognitive decline associated with the disease, rather than just treat symptoms, aducanumab could become the standard of care. That means it would set the bar for future candidates waiting in the developmental wings, from the likes of Eli Lilly, Roche and Eisai. 

Many patients, especially those in the early stages of the disease, would be eager to try aducanumab. There have been no new treatments for Alzheimer’s in 18 years (anyone remember Namenda?), let alone any FDA-approved, disease-modifying ones. With more than five million Americans suffering from Alzheimer-related dementia, and the subsequent devastating impact on families, the need is great. 

Yet there’s no shortage of doubts surrounding this monoclonal antibody. Perhaps the biggest one: Whether it actually works. 

Aducanumab is one of a number of experimental meds designed to clear clumps of brain beta amyloid, a sticky protein which accumulates in those with Alzheimer’s and is thought to be the main hallmark. The drug’s ability to remove plaque is not in question. Amyloid removal’s effectiveness as a strategy for treating the disease, though, very much is. 

Indeed, industry observers seem split as to whether Biogen has what analysts would call an “approvable data package.” The antibody has been dogged by controversial clinical results. 

One late-stage study was failed for futility in March 2019 before being declared positive by Biogen seven months later. Only then did the company suddenly unveil an analysis showing decline was 22% slower among some participants in the treatment cohort versus those in the placebo arm – specifically those subjects who were taking a high dose. 

The second of two big clinical trials failed to achieve the goal of slowing cognitive and functional impairment, although the drugmaker was encouraged by a subset of volunteers on higher doses. Could the key to effectiveness be giving patients a high-enough dose? That was Biogen’s conclusion, and what prompted it to reverse course and apply for approval. 

As a result, the outcome of FDA’s decision on whether to approve aducanumab for mild cognitive decline or early-stage dementia – perhaps the agency’s most important in years – is also cloudy. Some say that giving a thumbs-up based on one study’s positive post-hoc analysis, despite a second negative trial, would be not only unusual but probably unprecedented in neuroscience.

FDA signaled strong support for the med last November, even as a group of outside advisors to the agency gave the drug a scathing negative review. The agency is not bound by, but often follows, the advice of such panels. Biogen had been expecting a decision by March 7 of this year, but the agency delayed that review by three months and asked the company to submit additional analyses.

In neither of Biogen’s last two earnings calls has management provided any additional color on the nature of those additional analyses. The company did say it was setting aside $600 million as it gears up to launch aducanumab. It plans to target 600 high-volume Alzheimer’s centers. 

(TBWA\WorldHealth, the Omnicom-owned agency which won the aducanumab account this past year, declined to comment for this article.)

Being a first-in-class drug for treating the deterioration in brain function caused by the disease is a coveted marketing position. But there’s also no shortage of challenges facing Biogen if it becomes the category’s first-mover.

Source: Getty Images.

The mixed data on effectiveness have sowed a good deal of skepticism among prescribers. Doctors would have serious questions – not the least of which is the unusually premature termination of the two Biogen trials, and fundamentally whether they believe the benefits are worth the risks. Side effects include brain swelling and tiny bleeds in the brain.

And then there’s the price, and whether insurers will pay. Biogen has not set one yet, but the influential Institute for Clinical and Economic Review (ICER), which cited insufficient data to tell if the drug helps patients, nevertheless advised a price of between $2,500 and $8,000 a year per patient. One analyst speculated the drug, which is infused monthly, could cost $30,000 a year.

If approved, neither self-funded employers nor private insurers are likely to cover the medication “for the time being,” noted Seth Friedman, pharmacy practice and health plan services leader for pharmacy benefits consultancy Arthur J. Gallagher. He added that aducanumab is likely to fall under the medical (versus pharmacy) benefit based on its route of administration.

Given that most Alzheimer’s patients are in their 60s, the majority of would-be candidates for aducanumab are likely to be of Medicare age, Friedman said. “Knowing that this is a first-of-its-kind therapy, Medicare will have to cover it,” he wrote by email. He cautioned, however, that “there will be significant hurdles a patient will have to go through to gain access to the therapy due to a lack of proof points that the medication actually does provide a benefit.”

Roughly 88 million Americans 55 and older may be eligible for initial screening for a drug targeting the early stages of decline, according to a 2017 analysis by Rand Corp. Of those, 2.4 million might ultimately be eligible for therapy because they have mild cognitive impairment and abnormally high amyloid levels. Cigna chief clinical officer Steven Miller put the eligibility range closer to 1.2 million to 1.4 million.

In terms of additional challenges, the Rand study cited inadequate infrastructure for amyloid imaging to diagnose patients, which is done primarily through PET scanning; a lack of specialists; and too few infusion centers. Biogen CEO Michel Vounatsos acknowledged as much during an investor call in April, calling the availability of specialists and diagnosis capabilities “a bottleneck.”

Nevertheless, pent-up demand from an influx of patients could push U.S. sales of aducanumab to $7.5 billion in 2025, according to an average of analyst forecasts. Whether it becomes one of the world’s best-selling drugs or a biotech footnote remains, in sports betting parlance, a pick’em.