Lawmakers Probe ‘Anomalies’ in Biogen Alzheimer’s Approval

Leaders of two congressional committees probing the approval of Biogen Inc.’s new Alzheimer’s drug pressed the Food and Drug Administration for more information on “apparent anomalies” in the agency’s review of the $56,000-a-year therapy.

The Democratic leaders of the House Energy and Commerce Committee and the Committee on Oversight and Reform said in a letter to the agency that “significant questions remain” about the June approval of Aduhelm, even after FDA officials met with committee staff in July and provided documents.

Minutes from a meeting of an internal FDA body that the committees obtained showed one agency staffer warned that approving the drug could lead to millions of patients taking it without any benefit and even risking harmful side effects.

The congressional inquiry adds to pressure on the U.S. agency charged with regulating products that account for one-fifth of consumer spending.

The FDA has been without a permanent leader since January, and Acting Commissioner Janet Woodcock won’t be nominated for the permanent role, people familiar with the matter have told Bloomberg. The regulator is set to review plans to offer booster doses of Covid-19 vaccines that the Biden administration is pushing -- a goal some scientists see as driven more by politics than evidence. Top officials involved in that review are leaving the FDA.

The lawmakers’ letter suggests they are closely scrutinizing the FDA’s decision to approve Aduhelm through an accelerated pathway based on evidence that it reduces levels of an abnormal protein called amyloid. The drug, which could wind up costing the U.S. health system billions of dollars annually, hasn’t been proved to slow patients’ cognitive decline.

In an emailed statement, an FDA spokesperson cited the devastating impact of Alzheimer’s disease and said that the agency “recognizes the need for new therapies and used a science-based approach” that took into account patients’ perspectives on the benefits and risks of Aduhelm. “As always, the FDA will work with Congress to respond to any requests for documents or information, including the recent Chair’s letter request,” the agency said.

Woodcock requested a separate inspector general review of the agency’s interactions with Biogen, which is ongoing, the agency said.

Internal Dissent

The FDA approved Aduhelm over the objections of the agency’s outside scientific advisers and after two large-scale trials to gauge the drug’s efficacy were halted early because they were deemed unlikely to work.

Later analysis by Biogen suggested patients in one trial getting a high dose had a slower rate of cognitive decline, while the other trial showed no effect.

The letter from Representative Frank Pallone Jr. of New Jersey and Representative Carolyn Maloney of New York offered a detailed narrative of the controversy over Aduhelm’s approval. It highlighted dissenting views among FDA staff and outside advisers who opposed approval.

Members of one internal FDA group concluded that another clinical trial was needed to determine the drug’s benefit, according to meeting minutes obtained by the committee and cited in the letter.

Approval of the drug could “result in millions of patients taking aducanumab without any indication of actually receiving any benefit, or worse, cause harm” from side effects, one member of the Medical Policy and Program Review Council said, according to the letter.

The letter also questioned the agency’s interactions with Biogen during the review process. The FDA told committee staff in a briefing that it was common for agency officials to have informal conversations with drugmakers seeking approval for medications. 

Not all of those interactions with Biogen were memorialized, diverging from the agency’s guidelines, according to the letter.

The FDA is internally reviewing its collaboration with Biogen, in addition to the inspector general review.

Surrogate Measures

The letter also pressed the FDA on what evidence it relied on for the critical decisions that led to the drug’s approval.

Regulators have sometimes approved new drugs based on what are known as surrogate endpoints -- alternatives to measuring actual changes in patients’ disease --when such biological markers are clearly linked to clinical benefits.

But that’s not the case with amyloid, the committee chairs wrote. And the possibility of using accelerated approval based on amyloid levels wasn’t presented to the agency’s advisory committee, the letter notes.

In approving Aduhelm, the FDA waded into a decades-long unresolved debate over what causes Alzheimer’s disease. The FDA judged that reduction in amyloid was “reasonably likely” to translate into clinical benefits for patients. It ordered Biogen to do an additional trial to confirm the benefits.

Slow Rollout

The continuing controversy is also likely to cast a shadow over Biogen, which is heavily dependent on Aduhelm for growth. 

Already, some major medical centers are refusing to use the therapy. The company hasn’t yet published the results of its two final-stage trials in a medical journal, or announced details of a required follow-up study to confirm that the drug slows cognitive decline, although it says it is working on both.

Biogen has said the drug may be appropriate for up to 2 million people in the U.S. with early-stage Alzheimer’s, though the company expects fewer to get it. 

The high cost of the medication, large patient population and uncertainty over the evidence have combined to pose an unprecedented dilemma for the U.S. Medicare program, which is now evaluating how to cover the drug.

Political Controversy

For the FDA, the congressional scrutiny follows a period of high-stakes decisions on Covid-19 treatments and vaccines that put the agency in the center of national politics.

Concerns about the FDA’s vulnerability to political pressure heightened when then-President Donald Trump pushed for approval of Covid vaccines before the November election. Meanwhile, Trump touted unproven treatments for the illness, such as hydroxychloroquine and immune factors taken from the blood of recovered patients called convalescent plasma. 

The decisions have raised questions about what level of evidence is needed to evaluate medical advances with consequences for patients’ lives and billions of dollars at stake for companies.

Until it approved Aduhelm, the FDA itself never gave any clear public indication it would approve an Alzheimer’s drug based on amyloid lowering alone. 

In its letter to the FDA, the congressional committees zoomed in on this issue, asking the agency to specify “what body of evidence” it used to determine amyloid plaque could be a surrogate endpoint, and whether it considered bringing the question about using amyloid as a surrogate to an outside advisory panel.

The committees are seeking responses by Sept. 16.

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