By Joseph Walker
U.S. health regulators approved the first new Alzheimer's drug in nearly two decades, casting aside doubts about the therapy's effectiveness.
The approval Monday of the therapy, which has the molecular name aducanumab and will be sold as Aduhelm, marked a watershed in Alzheimer's drug research after billions of dollars in investment. Maker Biogen Inc. developed the therapy to do what previously approved Alzheimer's medicines can't: slow the memory-robbing march of the disease.
The U.S. Food and Drug Administration, explaining its decision, said scientific evidence indicated Aduhelm reduces a sticky substance in the brain called amyloid -- which is associated with Alzheimer's -- and is likely to produce a benefit to patients.
The drug's sale offers hope to millions of people dealing with Alzheimer's and their caregivers, given the lack of good options for treatment. Yet Aduhelm's impact may be limited. Doctors who say they will prescribe the drug caution it won't help all patients, particularly those with more advanced disease. Some patients eligible for treatment may face $10,000 or more in annual out-of-pocket costs, health insurer Cigna Corp. estimates.
In addition, some doctors say the evidence supporting the drug's efficacy is limited and recommended against its approval.
The drug is a potential blockbuster for Biogen. Its approval comes at a critical time for the biotech, which is coping with declining sales and the loss of patent protection for its biggest-selling drug, Tecfidera, a pill for multiple sclerosis.
Biogen has said it expects aducanumab sales to be modest this year as it launches the drug, and to start growing thereafter. Analysts polled by FactSet project sales of $62.7 million in 2021, $603.2 million in 2022 and $1.6 billion in 2023.
Biogen shares soared 43% after being halted earlier in Monday's session, adding $17.3 billion in market value. The Nasdaq Biotechnology Index rose 4%, on pace for its best day since Nov. 4, 2020.
"This historic moment is the culmination of more than a decade of groundbreaking research in the complex field of Alzheimer's disease," said Biogen Chief Executive Michel Vounatsos. "Together with the healthcare community, we are ready to bring this new medicine to patients and begin to address this growing global health crisis."
Biogen priced the newly approved drug higher than analysts expected. The company said it would charge about $56,000 a year per patient.
A preliminary analysis conducted by the Institute for Clinical and Economic Review, a nonprofit research and advisory group, said the drug could be cost-effective at a per-patient price of $2,500 to $8,300 a year.
Alzheimer's is a progressive degenerative disease that slowly robs people of their memory and the ability to care for themselves.
About six million people suffer from Alzheimer's in the U.S. Of those, as many as 1.4 million could be eligible to take Aduhelm, according to estimates by Cigna.
There were 121,499 deaths from Alzheimer's in the U.S. in 2019, up 54% from a decade earlier, according to the U.S. Centers for Disease Control and Prevention. After accounting for age and population growth, per capita deaths grew 23% over the period.
Despite considerable effort and investment, researchers have struggled to find drugs that prove to treat Alzheimer's. One drug after another aiming to slow the progression of the disease has failed in testing.
The FDA last approved a new Alzheimer's drug in 2003. Approved treatments, including the drugs Namenda and Aricept, can help reduce symptoms temporarily, but don't change the underlying course of disease, according to regulators.
The FDA granted Aduhelm an accelerated approval, a mechanism for getting drugs to patients faster than they otherwise would. The FDA said it was requiring Biogen to conduct a post-approval study to confirm the drug's benefit, and could take steps to remove it from the market if the drug doesn't work as intended.
Biogen developed Aduhelm to treat people with mild cases of cognitive impairment or dementia whose brains have accumulated beta amyloid, which many researchers believe plays a significant role in Alzheimer's disease for many patients.
"The clinical trials for Aduhelm were the first to show that a reduction in these plaques -- a hallmark finding in the brain of patients with Alzheimer's -- is expected to lead to a reduction in the clinical decline of this devastating form of dementia," said Patrizia Cavazzoni, who heads the FDA division that regulates drugs.
The FDA's approval doesn't specify which patients should be eligible to receive Aduhelm. Biogen said it would market the drug to customers based on the early-stage patients with amyloid deposits studied in its clinical trials.
"We have demonstrated efficacy for the earlier population.... For the others, we don't know," Mr. Vounatsos said in an interview. "This will be the position of the company, to engage with the customers based on our data, and based on the population treated."
Doctors said they expect strong demand for the medicine.
"I will no doubt field dozens, if not hundreds, of phone calls within the first day or week," said Richard Isaacson, director of the Alzheimer's Prevention Clinic at Weill Cornell Medicine and New York-Presbyterian hospital.
Biogen faces hurdles getting the drug to all the patients interested in taking it, says Dr. Isaacson, who is also a paid consultant to the company.
Before prescribing it, doctors will want to first make sure their patient's brain has amyloid buildup, which typically requires an imaging scan or spinal tap that usually aren't covered by medical insurance, Dr. Isaacson said.
Unlike other Alzheimer's drugs delivered in pills that can be picked up at a pharmacy, Aduhelm requires monthly infusions at a clinic. Patients will require monitoring with magnetic resonance imaging, or an MRI, to guard against small brain bleeds, a potential side effect of the drug, Dr. Isaacson said.
"There's going to be a lot of education required, and a lot of logistical roadblocks," he said.
In clinical trials, 41% of Aduhelm-treated patients had side effects detected by MRIs in which their brains had small bleeds, or hemorrhages, or an accumulation of fluid, according to the FDA. Most patients didn't suffer any symptoms from the side effects; among the 24% who did, the most common was headache. The FDA advised using MRIs to monitor patients for the side effects.
The drug also faces skepticism from some doctors over its unusual and controversial path to approval.
In 2019, Biogen halted two studies of the drug after determining that they were unlikely to be successful, only to reverse course several months later after reviewing additional data.
The company said it would seek approval based on the discontinued studies after discussing the matter with the FDA.
In one of the two studies, patients taking Aduhelm had a 22% reduction in cognitive decline compared with patients taking placebos. The drug failed to show a benefit in the second study, but a detailed breakdown of the results indicated the drug was effective when given at the highest dose for extended periods, Biogen said.
Some FDA officials appeared to agree with Biogen's analysis, giving a positive medical review of the drug during a meeting of independent experts convened by the agency to discuss whether the agency should approve the drug. The agency's statistical expert gave a more downbeat review, citing conflicting trial data.
The outside panel of experts rejected supporting the drug. They said Biogen should conduct another large study to prove the drug's benefit before it was approved.
"There is no persuasive evidence to support approval of aducanumab at this time," wrote three of the FDA's independent experts in the Journal of the American Medical Association in March.
Dr. Cavazzoni said the FDA decided to approve the drug, despite uncertainty regarding its benefit, due to the strong need for Alzheimer's treatment and an expectation that the drug's ability to reduce amyloid will lessen cognitive decline.
Jason Karlawish, an Alzheimer's specialist at the University of Pennsylvania, said he thinks the FDA shouldn't have approved the drug because of the lack of convincing evidence.
Yet he said he would still prescribe the drug to patients who want it after discussing with them its risks and benefits.
"I've chatted already with some of my patients, and some are interested and others say it doesn't sound like something I'd want to do," said Dr. Karlawish, co-director of the Penn Memory Center.
Cigna will likely cover the drug for people who match the patients studied in Biogen's clinical trials -- those with early-stage Alzheimer's and amyloid buildup in their brains -- said Steve Miller, Cigna's chief clinical officer.
Most Alzheimer's patients are covered by Medicare, and their out-of-pocket costs could be significant, depending on their coverage, because of so-called coinsurance payments that require patients to cover a percentage of certain health costs, Dr. Miller said.
"The out-of-pocket testing costs could be a real barrier for those patients who lack the financial means," said Dr. Miller.
Cigna estimates that patients with traditional Medicare insurance could be on the hook for more than $10,000 a year in coinsurance and copayments for the drug and amyloid testing, Dr. Miller said. Additional costs for people with supplemental Medigap insurance or commercial coverage through Medicare Advantage could reach up to $4,000 annually.
Dr. Miller said patients may be eligible for financial assistance to cover the extra costs through nonprofit foundations, which are often funded by drugmakers.
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