FDA approves Biogen’s Alzheimer’s drug, the first new medicine for the disease in 18 years

The agency rebuffs its outside experts, who had recommended against approving the Cambridge company’s controversial treatment.

Biogen has made the Alzheimer’s drug a key element of its long-term business strategy.John Tlumacki/Globe Staff/file

Federal regulators approved the first new medicine for Alzheimer’s disease in nearly two decades on Monday, a controversial drug from Biogen that is intended to slow the progression of the fatal illness in people with early symptoms but whose effectiveness is fiercely debated.

Seven months after an advisory panel of medical experts overwhelmingly concluded that the Cambridge-based biotech hadn’t presented enough evidence to recommend approval, the Food and Drug Administration rejected that advice and cleared the medicine, which is expected to be a multibillion dollar blockbuster.

The drug, called aducanumab during development and clinical trials, will be branded as Aduhelm and is likely to soon become a household name for the millions of Americans and their families affected by the mind-ravaging disease. It will require hourlong intravenous infusions every four weeks and carry a list price of $56,000 a year, according to Biogen.

Biogen’s share price soared after the decision, closing up more than 38 percent, at $395.85. But the approval seemed unlikely to end the debate on the drug, given that some scientists and physicians question whether it works.

Indeed, the greenlighting of the drug came with a caveat: Biogen must conduct a third late-stage clinical trial to confirm that Aduhelm produces cognitive benefits. While it is proven that the medicine removes a sticky substance called amyloid beta that accumulates in the brains of Alzheimer’s patients, Aduhelm’s effects on cognition and memory remain uncertain. Without that corroboration, the FDA said, Biogen will ultimately have to stop marketing the drug.

“Aduhelm is the first novel therapy approved for Alzheimer’s disease since 2003,” Dr. Patrizia Cavazzoni, director of the FDA Center for Drug Evaluation and Research, said in the eagerly awaited decision. “Perhaps more significantly, Aduhelm is the first treatment directed at the underlying pathophysiology of Alzheimer’s disease, the presence of amyloid beta plaques in the brain.”

The ruling delighted Alzheimer’s patients, their families, and advocates who have yearned for a drug more effective than the five previously approved. Alzheimer’s afflicts an estimated 5.8 million Americans and is the sixth leading cause of death in the United States.

Aduhelm was tested in patients with early-stage Alzheimer’s, who are estimated to number 2 million in the United States and thought most likely to benefit. But the FDA did not limit the drug’s use to any subset of patients.

“It is a new day,” said Harry Johns, president and chief executive of the Alzheimer’s Association, a national advocacy group, which had lobbied for approval in a campaign called “More Time” that enlisted celebrities such as Samuel L. Jackson. “This approval allows people living with Alzheimer’s more time to live better.”

“This is a dramatic turning point in the history of the fight against Alzheimer’s,” said George Vradenburg, cofounder and chairman of UsAgainstAlzheimer’s, another nonprofit group.

The decision was also a major triumph for Biogen. At several points in recent years, its Alzheimer’s drug development program appeared on the verge of failure

“This historic moment is the culmination of more than a decade of groundbreaking research in the complex field of Alzheimer’s disease,” said Michel Vounatsos, the company’s chief executive. “We believe this first-in-class medicine will transform the treatment of people living with Alzheimer’s disease and spark continuous innovation in the years to come.”

Biogen, which specializes in treatments for neurological disorders, has made the Alzheimer’s drug a key element of its long-term business strategy. The biotech added 1,700 employees to its global workforce in 2020, at least partly in anticipation of approval. It also built a $1 billion plant in Switzerland to help manufacture the medicine. It has more employees in Massachusetts than any other homegrown drug firm. About 2,400 of its 9,100 worldwide employees work in the state, according to a report last year by the Massachusetts Biotechnology Council.

The FDA cleared the drug under a less common “accelerated approval pathway” reserved for medicines that fill a serious unmet need. The FDA typically uses this approach when regulators are uncertain about the clinical benefits of a drug and rely on another yardstick that suggests it would help patients. In this case, that was Aduhelm’s reduction of amyloid plaque.

But several prominent doctors were surprised and distressed by the decision, which came amid intense pressure from families of people with Alzheimer’s and their advocates. Some physicians remain unconvinced that the medicine works, given contradictory outcomes in two late-stage clinical trials.

Dr. Jason Karlawish, co-director of the University of Pennsylvania’s Memory Center, said he understands the urgency behind the push for Aduhelm but believes the data do not clearly show that it works.

“Desperation should drive funding for scientific research and not drive the interpretation of scientific data,” he said.

Dr. Aaron Kesselheim, a professor of medicine at Harvard Medical School and one of 10 experts on the 11-member advisory committee that resoundingly recommended rejection of the drug, said regulators have “set a dangerous precedent for the low level of data needed to support efficacy in treatments” for Alzheimer’s.

Aduhelm is not without risks to patients, critics noted. Three out of 10 patients who received a high dose in clinical trials had brain swelling detectable on an MRI scan. That didn’t usually cause serious symptoms, but temporarily led to increased confusion and falls in some patients. The treatment will require regular imaging to detect potential brain swelling.

Dr. Andrew E. Budson, chief of cognitive and behavioral neurology at the Boston VA Health Care System and associate director of Boston University’s Alzheimer’s Disease Center, participated in the clinical trial and said some of his patients had to stop taking the drug because of brain swelling.

“It makes me uncomfortable giving a drug known to have toxicity without a known benefit,” said Budson, who called the approval “premature.” Still, Budson said he would prescribe the medication to patients who fully understand its risks and uncertain benefits. But he will insist on follow-up MRI scans to detect any swelling.

On the other hand, Dr. Stephen Salloway, director of neurology and the Memory and Aging Program at Butler Hospital in Providence, R.I., said the brain swelling is typically short-lived and easily managed. Salloway, who has been studying aducanumab for many years and said he received $11,000 from Biogen for consulting in the past year, welcomed the FDA decision. “It’s a turning point which I hope will open a new treatment era for Alzheimer’s,” he said.

Catherine Pearson of West Kingston, R.I., has taken the medication for five years through the study site run by Salloway, according to her daughter, Martha Langer. Langer said her mother, who turns 83 next week, has declined somewhat during that time. She lives with another daughter, but still enjoys her grandchildren, volunteering at the senior center, exercising, and knitting. “I feel the drug is helping to stave off a rapid decline,” Langer said.

Aduhelm is a monoclonal antibody made from the immune cells of older people with no or uncommonly slow cognitive decline. Studies indicate it does remove amyloid plaques, but it’s uncertain whether that slows the disease process that ultimately kills brains cells and affects memory and thinking. Scientists have disagreed for years about whether amyloid causes the disease or results from it.

The drug’s odyssey has been marked by soaring hopes and disheartening setbacks that have sent Biogen’s stock valuation swinging by billions of dollars in recent years. After the medication showed promise in 2015, Biogen launched two major trials, but those were halted in March 2019 after an independent monitoring panel concluded the drug didn’t appear to be working.

In a stunning reversal in October 2019, Biogen announced that an analysis of additional data had led to the drug’s resurrection. In one of the trials, people given the medicine declined 22 percent more slowly on average than those who received a placebo. The other trial failed to reach its goal. Nonetheless, Biogen concluded that Aduhelm slowed cognitive decline and that the key to effectiveness was giving patients a high enough dose.

The FDA typically requires two convincing studies for a medication to be approved, but has made exceptions for deadly or devastating diseases for which there are no effective treatments. Biogen collaborated with a Japanese drug firm, Eisai, on Aduhelm.

The panel of outside medical experts that advised the FDA concluded overwhelmingly in a nonbinding vote in November that the drug makers — and some agency staffers who gave the drug a glowing appraisal — cherry-picked positive data and jettisoned negative results.

The FDA usually follows the guidance of its advisory committees. But when it goes its own way, it typically leans against approving a new product, according to a 2019 study in The Milbank Quarterly, a peer-reviewed health care journal, making Monday’s endorsement especially significant.

Critics have said clearing Aduhelm would erode the FDA’s credibility and could hinder the development of other Alzheimer’s drugs. If the drug were approved, detractors argued, it would make it hard to recruit Alzheimer’s patients for clinical trials for other drugs where some volunteers would get a placebo.

An influential drug-pricing watchdog group also recently took a dim view of the drug. Citing the conflicting study results, the Boston-based Institute for Clinical and Economic Review said in a draft report that, if approved, the drug should be priced at $2,500 to $8,300 annually, given its modest benefits and risks for complications.