FDA scientists appear to offer major endorsement of Biogen’s controversial Alzheimer’s treatment

STAT+ subscribers will have access to all-day coverage of the Friday advisory committee meeting to discuss Biogen’s Alzheimer’s drug, with regular updates on key presentations, interesting arguments, and eventually the outcome itself. If you’re a subscriber, you’ll be able to find that coverage here. To subscribe, click here. 

The future of aducanumab, Biogen’s treatment for Alzheimer’s disease, appears brighter after reviewers at the Food and Drug Administration indicated they believed the drug was sufficiently safe and effective.

In a lengthy document released Wednesday, FDA staff appeared to endorse approving the treatment, which would become the first new Alzheimer’s therapy in nearly two decades. The commentary, which provides the first glimpse at how FDA scientists view the oft-debated treatment, comes ahead of a Friday meeting of outside advisers, who will issue a nonbinding vote on whether to recommend aducanumab’s approval.

Biogen shares rose nearly 45% to $355, adding $17 billion to the company’s market value.

Biogen’s data from one large clinical trial were “robust and exceptionally persuasive,” FDA reviewers wrote, endorsing the drug’s effects on the cognition of Alzheimer’s patients. A second, nearly identical study did not show a significant benefit, but “upon closer review,” the FDA agreed with Biogen’s argument that the sum of all the data suggests aducanumab is helpful to patients.

The reviewers did not explicitly call for FDA approval, but the tenor of their remarks appeared to support Biogen’s case.

The FDA review seemed to alleviate two major concerns about aducanumab: the fact that its two pivotal studies had different results, and the possibility that a common side effect informed patients whether they received treatment or placebo.

On the first point, FDA reviewers wrote that a deep look at the data suggested that a small number of patients with rapidly progressing Alzheimer’s might have skewed the study. When their results are removed, the numbers favor aducanumab, which is consistent with other studies of the drug, reviewers wrote.

On the safety side, a frequent side effect of aducanumab is a painful but manageable swelling of the brain called ARIA. Outside experts worried that the side effect might effectively unblind the study, informing patients that they’d received the treatment and thus creating a bias in the study. But FDA reviewers said an analysis of the data did not suggest that ARIA biased the trial.

However, not every FDA reviewer was convinced by Biogen’s read of the data. Buried on page 255 of the agency’s briefing, statistical reviewer Tristan Massie concluded that the sole positive trial of aducanumab cannot outshine the negative one, writing that “there is no compelling, substantial evidence of treatment effect or disease slowing and that another study is needed to confirm or deny the positive study and the negative study.”

There are no current medicines capable of slowing the cognitive and functional decline that occurs in people with Alzheimer’s disease. If approved, aducanumab would be the first drug to reduce cognitive decline by targeting and eliminating clumps of a toxic protein called beta amyloid that are believed to destroy the brain. It would be a significant medical achievement.

It would also be a big deal for Biogen’s bottom line. People experiencing mild cognitive impairment or early signs of Alzheimer’s would be the most likely to benefit from a drug like aducanumab, if it reaches the market. But even restricted use would translate into blockbuster sales. Cowen estimates that 2.2 million Americans have mild dementia due to Alzheimer’s disease. If one-third of these people were treated with aducanumab, priced at an estimated $50,000 per year, sales would reach $36 billion annually, according to the health care investment bank.

AbbVie’s Humira was the top-selling medicine last year, with sales of $19.7 billion. Merck’s Keytruda was second, with 2019 sales of $11 billion.

Even if aducanumab is prescribed to a fraction of eligible patients, it could still be among the top-selling drugs of all time. Today, Biogen is criticized — and its stock penalized — for selling drugs that are losing market share to low-cost generics or newer, more potent competitors. Aducanumab, if approved, would turbocharge Biogen’s growth and fundamentally change the stock’s outlook for the better.