Aduhelm: House investigation says FDA approval process for Alzheimer’s drug is ‘riddled with irregularities’



CNN

A congressional investigation found the US Food and Drug Administration’s “atypical cooperation” in approving a high-priced Alzheimer’s drug was “riddled with irregularities.”

The report, released Thursday, was the result of an 18-month investigation by two House committees. She sharply criticizes Biogen, the manufacturer of the drug Aduhelm.

The report said Biogen set an “unfairly high price” for Aduhelm to “make history” for the company and viewed the drug as an “unprecedented financial opportunity.” Biogen estimated Aduhelm at $56,000 per year, although the actual impact on a wide patient population was unknown.

More than 6.5 million people in the US are living with Alzheimer’s, and that number is expected to rise to 13.8 million by 2060, according to the Alzheimer’s Association. The disease is the sixth leading cause of death in the United States. There is no cure and effective treatments are extremely limited. Prior to the June 2021 approval of Aduhelm, the FDA had not approved a novel therapy for the condition since 2003.

The investigation found that Biogen was planning an aggressive marketing campaign to bring the drug to market and intended to spend more than $3.3 billion on sales and marketing between 2020 and 2024 — more than 2½ times what it spent developing Aduhelm spent.

Dementia, including Alzheimer’s, is one of the “most costly diseases to society” according to the Alzheimer’s Association. In 2022 alone, Alzheimer’s and other dementias cost the United States $321 billion, including $206 billion in Medicaid and Medicare payments, the association says.

Aduhelm’s costs to patients and Medicare would be significant, the new report said. This was one of the key factors behind a sharp increase in Medicare premiums in 2022, according to the Centers for Medicare and Medicaid Services.

Pending “pushback” from providers and payers, the report said, Biogen also prepared a narrative to sell the drug’s value.

The Committee on Oversight and Reform and the Committee on Energy and Commerce noted that the collaboration between the FDA and Biogen in the drug’s approval process “has exceeded the norm in some respects.”

Biogen initially halted Aduhelm’s clinical trials in March 2019 after an independent committee determined it was unlikely to slow the cognitive and functional impairment — the decline in memory, language and judgment — associated with Alzheimer’s. But in June 2019, the FDA and Biogen formed a “working group” to see if the effort can be cut.

The investigation found that from July 2019 to July 2020, the FDA and Biogen participated in at least 115 meetings, phone calls, and lengthy email discussions, including 40 meetings, to steer Aduhelm’s potential approval. There may have been more meetings, but the committees say the FDA failed to follow its own documentation protocol.

The agency then worked with Biogen to draft a document that informed an independent advisory committee that met in November 2020. Study results were mixed, with only one showing a small benefit for patients.

At that meeting, no member of the committee voted to say the studies provided strong evidence that the drug was effective in treating Alzheimer’s.

According to a former FDA adviser who sat on the committee for several years, the meeting was unusual. Dr. Aaron Kesselheim told CNN in 2021 that the relationship between the FDA and the company is exceptional.

“There was an odd dynamic compared to the other advisory committee meetings I’ve attended,” the Harvard Medical School professor said. “There’s usually some distance between the FDA and the company, but in this case, the company and the FDA were in complete agreement in supporting the drug.”

When the FDA approved the drug, Kesselheim and two other members of the advisory committee resigned in protest. He later called it “probably the worst drug approval decision in recent US history.”

The FDA often follows the recommendations of the independent committee, but in this case it changed course and used its accelerated approval pathway, which sets a different standard of evidence that a treatment might work.

The committee members said senior FDA leadership informed them that the change in how the drug would be approved came after an April 2021 meeting of the FDA’s Expert Council, which the new report says brought “unfavorable feedback.” for the traditional approval process.

The FDA has also approved the drug for “people with Alzheimer’s disease,” a much broader demographic than what was covered in Biogen’s clinical trials.

Internal company documents said that Biogen accepted this broader indication “despite internal reservations regarding the lack of evidence of clinical benefit for patients in disease stages outside of clinical trials and an unknown safety profile,” the report said. Executives expressed concerns that the company could lose credibility and developed a communications strategy to deal with the “expected fallout,” the report said.

The committees recommended that the FDA document all of its meetings with drug sponsors, establish a protocol for briefing documents and advisory committees, and update its guidelines for Alzheimer’s drug development and review.

The committees also recommended that companies clearly communicate safety and efficacy concerns to the FDA and consider estimates made by outside experts when setting drug prices.

“The American people rely on the FDA to ensure the safety and effectiveness of the medications they take. As the number of patients and families affected by Alzheimer’s disease continues to increase, it is critical that the FDA and pharmaceutical companies follow established procedures and behave with the transparency necessary to earn public trust win,” the report reads.

The FDA said in a statement that its “decision to approve Aduhelm was based on our scientific evaluation of the data included in the application, which is described in the approval materials.”

The agency says it reviews the committees’ findings and recommendations, and that its own review found the interactions with Biogen were appropriate.

“It is the agency’s job to interact frequently with companies to ensure we have adequate information to make our regulatory decisions. We will continue to do so as it is in the best interests of patients. However, the Agency has already started to implement changes in line with the Committee’s recommendations.”

Biogen said in a statement Thursday that it had been “working cooperatively” with the investigation.

“Biogen has been committed to the discovery and development of therapies for Alzheimer’s disease for more than a decade. We have relentlessly focused on innovation to address this global health challenge, adapting to both successes and setbacks,” it said. “Biogen stands by the integrity of the actions we are taking.”

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