Biogen dumps dubious Alzheimer’s drug after profit-killing FDA scandal

Photo of author
Written By Sedoso Feb

Enlarge / The exterior of the headquarters of biotechnology company Biogen in Cambridge, Massachusetts.
Getty | Boston Globe

Biotechnology company Biogen is abandoning Aduhelm, its questionable Alzheimer’s drug that has floundered on the market since its scandal-plagued regulatory approval in 2021 and brow-raising pricing.

On Wednesday, the company announced it had terminated its license for Aduhelm (aducanumab) and will stop all development and commercialization activities. The rights to Aduhelm will revert back to the Neurimmune, the Swiss biopharmaceutical company that discovered it.

Biogen will also end the Phase 4 clinical trial, ENVISION, that was required by the Food and Drug Administration to prove Biogen’s claims that Aduhelm is effective at slowing progression of Alzheimer’s in its early stages—something two Phase 3 trials failed to do with certainty.

In the announcement, Biogen noted it took a financial hit of $60 million in the fourth quarter of 2023 to close out its work on Aduhelm, which the company at one point reportedly estimated would bring in as much as $18 billion in revenue per year.

The saga

But the data never appeared to support such lofty aspirations. The drug is intended to work against the clumps of misfolded beta-amyloid protein that accumulate in the brains of people with Alzheimer’s. Though a small, early clinical trial showed the drug could reduce plaques in the brains of people with Alzheimer’s, it initially failed two identically designed Phase 3 trials. The trials, which collectively enrolled nearly 3,300 patients, intended to evaluate if the drug could slow the progression of Alzheimer’s in its early stages.

In March 2019, the company announced that it was ending both trials after a futility analysis indicated that the drug wasn’t working. But later that year, Biogen stunningly reversed course, saying that additional data had rolled in from the trials after the March announcement. A new analysis of the data from one of the two trials indicated that a subset of patients given the highest dose showed a small benefit on cognitive tests—though the patients in the other trial still saw no benefit. The data also found that 40 percent of patients given the high dose developed brain swelling.

Biogen boldly submitted its data to the FDA for approval. In November 2020, a panel of independent advisors for the FDA voted resoundingly against Aduhelm’s approval. Ten of 11 committee members voted against the drug while the remaining member voted “uncertain.” After voting no, one member commented on the “incongruity” of Biogen’s presentation of the drug and the actual data. “It just feels to me like the audio and the video on the TV are out of sync, and there are literally a dozen red threads that suggests concerns about the consistency of evidence—a dozen,” the member said. The FDA, too, in its own statistical analysis of the data, concluded that “there is no compelling substantial evidence of treatment effect or disease slowing.”

In June 2021, the FDA nevertheless granted approval of Aduhelm. It was a move that shocked and outraged the advisory committee members and outside researchers, and drew attention from lawmakers. Three members of the advisory committee resigned in protest. One of them, Aaron Kesselheim, of Harvard University, wrote to then-acting FDA Commissioner Janet Woodcock that the FDA’s decision was “probably the worst drug approval decision in recent US history.” Meanwhile, noted pharmaceutical industry veteran and blogger Derek Lowe called the FDA’s decision “disgraceful.”

A Congressional investigation report released in December 2022 found the FDA’s review of Aduhelm was “rife with irregularities” and suggested that Billy Dunn, head of the FDA’s neuroscience office, had too-cozy a relationship with Biogen employees, finding “atypical collaboration and interactions.” Dunn stepped down from his role at the FDA in February 2023.

The fallout

But, amid the backlash over the FDA’s approval, Biogen moved forward with Aduhelm, announcing the drug’s list price soon after the regulatory green light. According to a report by Stat News, the company had hired consultants to help research the best price. Their final report suggested that a price between $15,000 to $20,000 a year would maximize the number of patients who could get the drug, while a price of less than $40,000 would limit pushback. A price over $40,000, on the other hand, would allow for “revenue maximization.” Biogen set the list price at $56,000 a year.

The price only added to the outrage and controversy. Some insurers refused to cover it. In April 2022, Medicare limited coverage only to those enrolled in a clinical trial. A month later, Biogen’s then-CEO Michel Vounatsos announced his resignation. Aduhelm was a flop, bringing in just $3 million in 2021, its first year on the market. In 2022, its sales weren’t big enough to be listed separately, and they were instead included in an “other” category, which totaled $13 million.

Along with ditching Aduhelm, Biogen, now under CEO Christopher Viehbacher, is shifting its priorities and will focus on its newer Alzheimer’s drug, Leqembi. Another anti-amyloid antibody drug, Leqembi yielded more convincing data of some benefit in clinical trials. But, the benefit was modest, and the drug, like Aduhelm, carries significant risks.

In Wednesday’s announcement, Viehbacher said: “When searching for new medicines, one breakthrough can be the foundation that triggers future medicines to be developed. Aduhelm was that groundbreaking discovery that paved the way for a new class of drugs and reinvigorated investments in the field.”

In a blog post on Wednesday, pharmaceutical industry veteran Lowe summarized the whole situation as a “debacle.”

The saga “ended up doing a lot of actual damage,” Lowe wrote, criticizing the company’s new focus on Leqembi, which he noted carries significant risks. “I think one of the reasons Leqembi was approved (and Lilly’s donanemab is likely to be, this year) is that [Aduhelm] was approved. I remain skeptical that these drugs will provide any real-world benefit, but I am not skeptical at all of the sales potentials for both of them.”

Source

Leave a Comment

. . . . . . . . . . . . . . . . . . . . . . . .