Biogen Inc. resurrected its Alzheimer's treatment after a secret meeting with a top government scientist, a pivotal moment in a back-channel campaign that started earlier and was far more extensive than previously known, according to former company employees and other people familiar with the effort.
The campaign culminated earlier this month with the Food and Drug Administration's approval of the medicine, called Aduhelm, perhaps the agency's most contentious drug ruling in decades. Over the objections of its scientific advisers and to the shock of the pharma industry, the FDA gave a green light to the first new Alzheimer's medication since 2003, one that could finally give millions of dementia patients a reason for optimism — and reap billions of dollars for Cambridge-based Biogen.
After the FDA's approval, the company's CEO, Michel Vounatsos, proclaimed on Biogen's website, “I have hoped for years that we would reach a moment like this.''
But Biogen executives were hardly passive players hoping for FDA approval. Two years ago, when Aduhelm's prospects appeared dead, the company mounted a secret campaign, code-named “Project Onyx," to breathe new life into the drug and persuade the FDA to give it the green light.
Central to their mission was an inside ally: Billy Dunn, the agency's top regulator of Alzheimer's drugs. For the plan to succeed, Biogen needed Dunn to become a supportive partner, more than an independent and potentially adversarial regulator. It worked. The FDA played an extraordinarily proactive role, even drafting a road map on how the company could win approval. Several experts said that relationship was not typical and raised serious concerns.
It was previously known that Biogen and the FDA worked together on Aduhelm.
But STAT has learned that the relationship began earlier than previously disclosed, in the spring of 2019, when a top Biogen executive quietly met with Dunn — seemingly in violation of FDA protocols — to enlist his support for a long-shot effort to get Aduhelm approved despite the apparent failure of two clinical trials. And a month later, FDA officials proposed using a regulatory shortcut to get the drug approved — though the agency has claimed it raised that option only this past March. To some inside Biogen, the FDA's tone made approval seem inevitable.
STAT has pieced together the 16-year odyssey from discovery to approval of Aduhelm, seemingly one of the most unlikely, and certainly far-reaching, outcomes in the FDA's history. It is also the story of how Biogen was pulled from the brink by the agency's decision, but only after the company was buffeted by a boom-and-bust business cycle, a gyrating stock price, and corporate infighting.
This story is based on interviews with more than a dozen people, including former Biogen employees, federal regulators, and scientists and executives who worked closely with Biogen or were familiar with the regulatory process, as well as on an examination of government documents.
Responding to a detailed list of questions for this story, a Biogen spokesperson said, “We respect and followed the FDA's guidance, regulations, and processes during the review of the Biologics License Application of Aduhelm. We are grateful to everyone who worked to clearly present our data, which led to the accelerated approval of the treatment."
The FDA declined to comment.
“I think it's terrific to have very close collaboration between the FDA and industry. Collaboration is essential," said Luciana Borio, a former acting chief scientist at the FDA. “However, FDA must remain impartial in its assessment of the science and the product." She added: “Close collaboration does not mean that you do whatever industry wants at the expense of what patients need."
Project Onyx was quietly launched inside Biogen at a time when it appeared to everyone outside the company that Aduhelm had joined the long roster of drugs for Alzheimer's that had looked promising but ultimately ended in disappointment and failure.
Biogen executives initially chose the code name “Project Phoenix," a reference to the mythological bird rising from the ashes. But after Biogen's lawyers objected, they settled on “Project Onyx."
Had anyone on the outside world known at the time, the plan might have seemed foolhardy given that in March 2019, a committee of independent physicians dispatched by Biogen to monitor its two large clinical trials of Aduhelm reported back with alarming news: An interim analysis based on data from the ongoing studies concluded the drug was not working as hoped. Statistically, the study monitors determined that Aduhelm — then known by its scientific name aducanumab — was “futile." The monitors recommended to Biogen that halting the trials was in the best interest of patients.
Biogen's executive team, including CEO Vounatsos and chief scientist Al Sandrock, received the news in one of the company's conference rooms. Biogen's head of research, Michael Ehlers, joined via phone from the Galápagos Islands. The mood was funereal. After poring over the findings of the independent data committee, Sandrock and Ehlers made the excruciating decision to discontinue the two clinical trials that had cost the company hundreds of millions of dollars. A public announcement was quickly prepared: Aduhelm was being shelved.
The news broke on the morning of March 21, 2019. Biogen's stock price fell 30 percent, chopping $16 billion from its market value.
Almost immediately, Biogen scientists dove into the halted studies to figure out what went wrong. Within weeks, they discovered something even more surprising: hints in the data that Aduhelm was actually effective against Alzheimer's. There was a possibility the drug might work, after all.
With that glimmer of hope, Sandrock reached out to Dunn, director of the Office of Neuroscience inside the FDA. The two men already had a longstanding professional relationship, and both were attending a neurology conference in Philadelphia. Sandrock sat down with Dunn for a previously unreported off-the-books meeting. The conversation had to be handled delicately, because drug makers normally share clinical data with regulators only in scheduled, documented settings — rules set out by FDA policy.
Though this was not a formal meeting, Sandrock wanted to let Dunn know that Aduhelm — publicly declared ineffective — might actually be slowing the progression of Alzheimer's, according to a source briefed on the meeting. And Sandrock wanted to know if Dunn would be open to helping find a way to get the drug approved.
It appears to have gone very well. That meeting, in the early days of May 2019, set in motion Project Onyx — a two-year pursuit that would change the course of Alzheimer's treatment, rescue Biogen's future, and set off a firestorm of criticism upon the FDA.
“It was clear that Billy Dunn was an ally, so the job for Biogen became figuring out how to support his efforts within the FDA," a former Biogen employee told STAT. The employee, like others in this story, spoke on the condition of anonymity to protect their business relationships.
Told by STAT of the meeting, Caleb Alexander, an epidemiologist at Johns Hopkins University and a member of the FDA advisory committee that reviews Alzheimer's drugs, said: “If there truly were a meeting that was off the record, or off the books, I don't believe that is FDA policy. The presence of an off-the-book meeting would reinforce concerns that this was a highly atypical relationship between a drug manufacturer and a regulator."
The FDA's support grew quickly. By June 2019, only a month after the crucial meeting with Dunn, agency officials in his Office of Neuroscience were so willing to advance Aduhelm that they proposed as one option a regulatory shortcut called “accelerated approval," according to meeting minutes read to STAT. The move stunned even Biogen's top executives, who had considered that out of the question for a host of reasons, including the fact that the FDA had never used the pathway for an Alzheimer's treatment.
This disclosure contradicts what the FDA has said publicly in recent weeks about how it came to consider the use of accelerated approval for Aduhelm.
An internal review document made public by the FDA last week claimed officials inside the agency first raised the possibility of an accelerated approval of Aduhelm during a meeting held this past March 31. In fact, Dunn's Office of Neuroscience proposed its use two years ago.
STAT provided the FDA a detailed list of questions for this story, including a request for comment from Dunn. The agency, through its chief spokesperson, declined to comment.
The moves inside the FDA to rally behind approving Aduhelm were highly unconventional, which was underscored by the repercussions after the agency signed off. Three panelists from an outside committee that recommended the FDA reject the drug resigned in protest, with one calling it “probably the worst drug approval decision in recent US history." The committee had voted overwhelmingly that the evidence for the drug's effectiveness was slim, and that even if it worked, it's clinical benefit appeared marginal.
Members of Congress pounced on Biogen for the drug's $56,000-a-year price, warning that it could bankrupt the Medicare program that administers injected drugs. Two House committees have scheduled investigational hearings, seeking answers from FDA officials about how a drug so disputed came to win approval.
Public Citizen, the government watchdog, has called for the resignations of three top FDA officials, including Dunn and Acting Commissioner Janet Woodcock, because of the approval.
On the other side, Alzheimer's patient advocacy groups praised the approval, celebrating the first new medicine for the devastating disease in 18 years. The Alzheimer's Association lobbied the FDA, urging the agency to approve Aduhelm. “Clearly, this is not a cure, and it is a marginal difference for people, but a marginal difference can make a real difference for people who have only the devastation of Alzheimer's to look to," said Harry Johns, the association's CEO, told STAT. On the day of the approval announcement, Biogen's stock price soared 39 percent.
The decision has shifted the landscape for Alzheimer's drugs, clearing the way for Eli Lilly to apply for approval of a similar medicine. But it has also spurred disbelief among some pharmaceutical executives. “This is a disaster on so many levels," said one, asking for anonymity to speak candidly about another drug maker. “I frankly cannot fathom how the FDA decided to approve a drug that seems to have more evidence that it causes harm than good."
This is an abridged version of a STAT special report. To read the full story, visit statnews.com.