The review leading to the 2021 approval of Alzheimer’s med Aduhelm was “rife with irregularities,” multiple congressional committees found in an investigative report issued as the Food and Drug Administration gears up to decide the fate of two similar drugs. 

The improprieties included a stream of poorly documented meetings between the FDA and drugmaker Biogen, “inappropriate” collaboration on an adcomm briefing document and a marketing playbook that was overly broad given a lack of clinical data on all Alzheimer’s patients, according to the report.

In addition, based on internal company documents surfaced during their probe, the committees heading the investigation noted that Biogen had expected “pushback” from providers and payers. However, the company set the launch price at $56,000 per year anyway in order to maximize revenue, despite knowing it would have a large financial impact on Medicare.

The conclusions are the latest in the soap opera surrounding Aduhelm, which some expected would head off the cognitive decline from Alzheimer’s, the memory-stealing disease whose patient burden is projected to grow from about six million people to as many as 14 million by 2060. 

Instead, once Medicare severely restricted reimbursement, Biogen abandoned the launch and saw paltry sales levels that paled in comparison to blockbuster forecasts.

The conclusions arrived on the eve of regulators’ decision for another treatment that targets amyloid plaque in the brain, Biogen and Eisai’s lecanemab, whose go/no-go is set for this Friday. Phase 3 data for Eli Lilly’s fellow amyloid-removal drug donanemab are expected in the second quarter.

The two committees that spearheaded the 18-month investigation — the Committee on Oversight and Reform, chaired by outgoing Rep. Carolyn Maloney (D-NY), and the Committee on Energy and Commerce, led by Rep. Frank Pallone (D-NJ) – launched their review into Aduhelm’s approval and pricing shortly after the drug won accelerated approval in June 2021. 

“I am hopeful these findings are a wake-up call for the FDA to reform its practices and a call to action to my Congressional colleagues to continue oversight of the pharmaceutical industry to ensure they don’t put profits over patients,” Maloney said in a statement.

Biogen canceled Aduhelm’s clinical trials in March 2019 due to an independent futility analysis showing that the drug was unlikely to slow cognitive and functional decline. In June 2020, the FDA and Biogen began a working collaboration to examine the data from the failed trials. 

Over the next 12 months, this working group held an “atypical” number of meetings, calls and email discussions – the report estimates at least 115 took place, although the exact number is unknown because at least 66 weren’t properly documented or archived. 

The working group also prepared a “joint briefing document” to FDA’s Peripheral and Central Nervous System Advisory Committee, a collaborative effort which had previously been reserved for use with oncology drugs.

When the adcomm met in November 2020, none of its members recommended approving Aduhelm. Yet, in the face of that no-confidence vote as well as internal concerns by FDA’s staff about inconsistencies in the drug’s clinical trial data, Aduhelm won accelerated approval from the FDA in June 2021 on the basis that the drug reduces amyloid-beta brain plaque. 

The committees’ staff held multiple briefings with FDA and pored over 500,000 pages of documents ranging from internal Biogen strategy documents, Biogen’s board materials and launch plans, as well as internal FDA correspondence. 

Results of an internal review of the FDA and Biogen’s interactions from spring 2021 show that the agency itself found that collaboration between its officials and the company was “atypical” but not inappropriately so, in light of the plight of the Alzheimer’s community.

Moreover, the committees reported that FDA and Biogen went after a broad label for Aduhelm — “all Alzheimer’s patients” — a far broader population than Biogen studied in its clinical trials. Still, the label was later narrowed.

What’s more, Biogen priced the drug at $56,000, an “unjustifiably” high price, lawmakers charged, given concerns about the drug’s efficacy, safety and affordability. Nevertheless, internal company documents showed, execs pushed forward with the price because they sought to “make history” with the drug launch

Additionally, Biogen estimated that out-of-pocket costs could run as high as 20% of their income for some Medicare patients. The company also projected that the drug could cost the public insurance program for seniors $12 billion in one year, or 36% of Medicare’s budget for physician-administered drugs and other outpatient services. Biogen later reduced the price by half.

Finally, the internal documents show, the biotech planned to spend more than $3.3 billion on sales and marketing for Aduhelm from 2020 to 2024, which is more than two-and-a-half-times what Biogen spent developing the drug. 

Its marketing plan focused on direct outreach to providers, patients, advocacy groups, payers and policymakers. The company forecast spending between $500 million and $600 million building out its sales force, with a focus on targeting physicians.

The committees urged the FDA to act with “all due urgency” to adhere to the FDA’s own internal guidance with regard to recording meetings and on “whether and when” it’s appropriate to collaborate with drugmakers in advance of advisory committee hearings. They also offered considerations for setting prices for the meds, in order to avoid what they called “sky-high launch prices.”

A Biogen spokesperson told The Wall Street Journal that it “stands by the integrity of the actions we have taken.” The FDA, for its part, said the agency fully cooperated with the investigation and that it has “already started implementing changes consistent with the Committee’s recommendations.”