A federal advisory panel on Friday concluded that Cambridge biotech Biogen had failed to prove its experimental medicine for Alzheimer’s disease was effective, potentially dooming a drug that had raised hopes among millions of people, and their families, who are affected by the devastating illness.
Although the 11-member committee never specifically recommended that the FDA reject the medicine, called aducanumab, the outside experts made it clear in a series of four votes that they believed that Biogen — and some FDA officials who guided the firm through the application process ― had cherry-picked positive clinical trial data and jettisoned negative results.
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Dr. Scott Emerson, a professor emeritus of biostatistics at the University of Washington and member of the panel, likened Biogen to a Texas sharpshooter who fires a shot at a barn and “then draws a target around the bullet hole.”
On perhaps the most telling question, the committee voted 10-0, with one “uncertain,” that Biogen had not proved that the positive late-stage clinical trial it relied on provided “primary evidence” to show that aducanumab was effective.
Several committee members criticized the FDA, saying agency analysts had glossed over the fact that another late-stage trial by Biogen found the drug ineffective. In a 343-page background document provided to the committee earlier this week, FDA analysts said the positive trial had provided “robust and exceptionally persuasive” evidence that the drug was beneficial. But an agency statistician took a much dimmer view in another document, saying that excluding data from the other, less positive trial would be “unscientific, statistically inappropriate, and misleading.”
Emerson took a similar view during the daylong meeting. He said he was distressed that “the FDA presentation today was so heavily weighted to giving the same conclusions [Biogen] did” without considering the conflicting evidence.
Although the votes of the committee were nonbinding, the agency rarely overrules its advisory boards. One notable exception occurred in 2016 when the FDA disagreed with a panel and its own staff and approved Exondys 51, a treatment by Cambridge-based Sarepta Therapeutics for Duchenne muscular dystrophy. That decision elated families of boys with the rare genetic disease but stunned critics who said the agency appeared to bow to political pressure. A nonprofit Boston-based watchdog group last year raised doubts about the benefits of Exondys 51, which carries a yearly pricetag of about $300,000, although Sarepta and relatives of patients disputed that.
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The FDA has promised to make a final decision on aducanumab by March 7. About a dozen people who suffer from tAlzheimer’s or care for people with the disease urged the committee to recommend the drug be approved after telling poignant stories of the devastation that the disease has wrought.
“It’s time for those of us living with Alzheimer’s to hear some good news,” said Pam Montana, who retired from her job as an Intel executive in California in 2016 after being diagnosed with early-onset Alzheimer’s. “We need hope that there will be a cure.”
Biogen’s chief executive, Michel Vounatsos, said in a statement after the meeting that the company “appreciated the opportunity to share our data with the advisory committee, and we will continue to work with the FDA as it completes its review of our application.”
Aducanumab is a monoclonal antibody made from the immune cells of elderly people with no or uncommonly slow cognitive decline. Researchers designed it to remove a sticky substance from the brain called beta amyloid that some scientists believe contributes to Alzheimer’s disease.
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If approved, the drug would be the first new medicine to treat the disease since 2003. Unlike current medicines on the market, aducanumab is supposed to address the underlying cause of the disease rather than merely to ease symptoms. In contrast to Alzheimer’s drugs like Namenda and Aricept, which come in pills, aducanumab would be administered intravenously for about an hour every four weeks.
It would also be the first drug marketed to slow cognitive decline in people with early Alzheimer’s, a population exceeding a million people in the United States. An estimated 5.8 million Americans age 65 and older are living with Alzheimer’s, making it the sixth-leading cause of death in the country, according to the Alzheimer’s Association. Given those huge numbers, a new effective Alzheimer’s drug would be a certain blockbuster, generating sales of billions of dollars a year.
Biogen, which specializes in medicines for neurological diseases, has the largest workforce of any drug firm based in Massachusetts, with about 2,400 employees. It has been working on a drug to treat Alzheimer’s for years, and aducanumab has had a bumpy ride.
In March of last year, the company abruptly ended a pivotal trial of the drug after an early look at results indicated it did not provide a significant benefit. The news sent Biogen stock into a freefall, with the firm losing a staggering $18 billion of its value in a single day.
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Seven months later, the biotech stunned many by reversing itself and saying it had decided to seek FDA approval after all. Biogen executives said their initial conclusion was wrong and that a look at a larger set of data showed that patients treated with the drug showed improvements in memory, orientation, and language.
After the FDA posted background documents with glowing reviews of aducanumab on its website Wednesday, Biogen’s share price soared nearly 44 percent. The company ended the day with a market cap of $54.7 billion, up more than $16 billion.
Given the stakes of Friday’s advisory committee hearing, trading of Biogen stock was suspended before the panel met.
The committee heard from several people who said family members had participated in Biogen’s clinical trials and appeared to benefit from aducanumab.
Kim Bonham, of Philadelphia, said her husband, Kevin, was diagnosed with Alzheimer’s at the age of 58 but quickly got into Biogen’s trial. His reading skills and ability to concentrate improved, and he was able to tell time on his analog watch again. But when the trial stopped in March of 2019, she said, those skills faded in eight months. After the trial resumed in October of last year, he began getting infusions again, and she believes he has improved.
“We are asking you from the bottom of our hearts to consider bringing aducanumab to market,” she said.
Several committee members said they were moved by such accounts but felt Biogen should launch another clinical trial to resolve the conflicts between the two late-stage studies. They said that approving a drug without clear-cut evidence of its benefits could jeopardize subsequent efforts to develop an effective medicine.
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Jonathan Saltzman can be reached at jonathan.saltzman@globe.com.