Biogen's CEO Becomes a Political Sacrifice

"Investors toasted Biogen CEO Michel Vounatsos last June after the Food and Drug Administration approved the company's Alzheimer's monoclonal antibody, Aduhelm -- the first treatment that has been shown to slow progression of the debilitating disease. It was expected to become a blockbuster in short order.

But those hopes were dashed as Aduhelm came under political attack, culminating in the Center for Medicare and Medicaid Service's refusal last month to pay for it outside of clinical trials. Most patients will have to pay $28,200 a year out of pocket.

Aduhelm sales have since totaled a mere $5.8 million while Biogen's stock price has fallen by half.

On Tuesday Mr. Vounatsos announced his resignation, a casualty of the left's crusade against high drug prices.

 But those prices are crucial to innovation. Other pharmaceutical CEOs may think twice about staking a big bet on a promising drug lest it become a political target.

Mr. Vounatsos's big mistake was prematurely halting Aduhelm's two late-stage trials. An early-stage trial showed that the drug removed a significant amount of amyloid plaque, a hallmark of the disease, from patients' brains. But a midpoint review of late-stage trials in 2019 didn't show a significant cognitive benefit.

Dozens of Alzheimer's drugs have failed in clinical trials, so experts weren't surprised. The shocker came several months later, when Biogen announced it would seek FDA approval based on a more detailed post hoc analysis that did find a significant clinical benefit.

Those who received a high dose of the drug in one trial showed a 71% reduction in amyloid plaque on average after 18 months, as well as a 25% to 28% smaller decline in memory and problem-solving compared with the placebo group.

Patients in the second trial didn't appear to benefit, but they were on a high dose of the drug for less time. Treatment benefits appear to accrue with time.

So while results from the two trials appeared to conflict, they could also easily be reconciled. The FDA decided to reconcile them by granting Aduhelm accelerated approval, which allows the agency to provide patients earlier access to drugs that "treat serious conditions" and "fill an unmet medical need based on a surrogate endpoint."

What is a surrogate endpoint? Some sort of biomarker like a lab measurement that is believed to predict a treatment benefit. The FDA often grants cancer drugs accelerated approval based on tumor shrinkage rather than survival benefits, which can take many years to measure. In Aduhelm's case, the FDA determined amyloid levels in the brain were a reasonable proxy. This determination, the FDA explained, was rooted in evidence from other clinical trials.

Yet many liberals accused the FDA of compromising its rigorous standards and caving in to pressure from desperate patients. Democratic lawmakers in June announced an investigation to address "serious concerns about the steep price . . . and the process that led to its approval despite questions about the drug's clinical benefit."

Sens. Elizabeth Warren (D., Mass.) and Bill Cassidy (R., La.) also warned that potential Medicare spending on Aduhelm "tests the program's resiliency." "FDA approval does not guarantee Medicare coverage," they added, "and so the program will need to answer an enormous question: should it cover a new and expensive Alzheimer's medication, and if so, how?"

CMS responded last month: It will cover Aduhelm and future Alzheimer's amyloid drugs receiving accelerated FDA approval only for patients who enroll in randomized controlled trials. That will effectively limit access to a few thousand patients, some of whom will get a placebo.

This is the first time CMS has restricted access to an FDA-approved drug in such a way. It's not clear Mr. Vounatsos could have done anything differently to appease the drug's critics. Last year he slashed the price in half ($28,200 is the reduced amount) and agreed to accelerate a follow-up randomized controlled trial to confirm its benefits.

Democratic lawmakers don't always insist that the FDA adhere strictly to standards of efficacy. Some now demand that the FDA authorize Moderna's vaccine for toddlers immediately, even though it didn't increase protection against hospitalization compared with a placebo in Moderna's trial -- no child in either group was hospitalized -- and showed only a small reduction (37.5%) in infections among those 2 to 5 -- lower than the 50% standard the FDA set for approving Covid vaccines.

But children produced antibodies -- that is, a surrogate endpoint -- similar to those of young adults. Ergo, the theory goes, the vaccine may confer larger benefits to children than demonstrated in clinical trials. But that's conjecture.

The case is much stronger for giving Alzheimer's patients access to a treatment that can slow a debilitating and deadly disease. Few children die of Covid. Hundreds of thousands of elderly people die each year of Alzheimer's and its complications. Mr. Vounatsos won't be the only casualty of the left's war on high drug prices." [1]

1. Biogen's CEO Becomes a Political Sacrifice
Finley, Allysia. 
Wall Street Journal, Eastern edition; New York, N.Y. [New York, N.Y]. 05 May 2022: A.17.