The Food and Drug Administration on Monday approved a high-profile Alzheimer's drug, a controversial decision to green light the first new drug to slow the mind-robbing disease in nearly two decades.
The FDA's landmark approval of Biogen's aducanumab will require the drug company to conduct a post-approval study to monitor its effectiveness. The company said it will market the drug under the name Aduhelm.
The FDA's approval comes despite a contradictory recommendation from experts on the agency's Peripheral and Central Nervous System Drugs Advisory Committee, which last November cited conflicting results from two main clinical trials. The FDA, however, decided the drug may provide "meaningful therapeutic benefit over existing treatments," Dr. Patrizia Cavazzoni, director of FDA's Center for Drug Evaluation and Research, said in a statement.
The FDA granted accelerated approval of the drug, a standard to provide earlier access to patients with serious diseases with an unmet need. Despite "residual uncertainty" about the drug's benefit, Cavazzoni said, the agency concluded the drug met the agency's standard as potential benefits outweighed the risks.
Alzheimer's patient advocacy organizations praised the FDA's decision to approve the drug, which is administered by IV once every four weeks to slow decline in people with mild memory and thinking problems. Biogen said the list price would be $4,312 per treatment for a person of average weight – a price that would total about $56,000 per year, before insurance.
Harry Johns, Alzheimer’s Association president and chief executive officer, said his organization will focus on ensuring eligible patients have access to the drug and Medicare and private insurers cover testing and treatment.
Johns said the approval is the culmination of years of efforts to fund research of new treatments to slow the deadly march of Alzheimer's and other forms of dementia. The group estimates about 6.2 million Americans are afflicted with Alzheimer's.
"It really is a new day for all of our constituents, so many who already have lost family members, so many who face Alzheimer’s today," said Johns. "I want to make clear this is not a cure. As in the case of so many other diseases, the first treatments are imperfect, but they can and do make a difference and that is very meaningful to those families."
Still unanswered are thorny questions about how doctors determine if a patient is eligible for the drug and whether patients will need to get expensive PET scans to detect amyloid beta plaque deposits in their brain.
"It’s going to be months before we know if anybody is going to pay for medication, the infusions, the MRIs, the PET scans that will be needed," said Dr. Pierre Tariot, director of the director of Banner Alzheimer’s Institute in Phoenix. "Who will be trained to disclose the amyloid information to the patient and the families? There’s a lot that has to be done."
The drug is a monoclonal antibody that works by removing amyloid beta from the brain. Scientists have long theorized plaques formed by these protein deposits in the brains of Alzheimer's patients kill brain cells and lead to cognitive decline. However, drug companies have invested billions on drugs that target or remove amyloid but have not yet proven the drugs slow memory and thinking problems.
The FDA said the approval of Aduhelm is based on a "surrogate endpoint" that the drug effectively removed amyloid plaque from the brain. Such an endpoint predicts but does not measure whether the drug will slow memory or thinking decline.
Biogen will be required to conduct a post-approval study to verify the drug works and monitor for known side effects such as brain swelling. If the study does not verify the drug’s clinical benefit, the FDA could remove the drug from the market.
In a document released last November, FDA reviewers gave a mostly positive assessment of the drug, finding "substantial evidence of effectiveness" as a treatment for Alzheimer's disease. However, in the same document, another reviewer raised questions about statistical methods, was not convinced of the evidence and recommended another trial.
Biogen CEO Michel Vounatsos said the authorization follows more than a decade of groundbreaking research of Alzheimer’s disease.
"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," Vounatsos said. "We are grateful for the contributions of thousands of patients and caregivers who participated in our clinical trials, as well as for the dedication of our scientists and researchers."
Aduhelm has stirred considerable debate among Alzheimer's researchers for its unconventional path to approval.
After a small, initial study showed the monoclonal antibody was safe, Biogen launched two large trials in 2015 to gauge the effectiveness of the drug, which removes beta amyloid plaques from the brain of an Alzheimer's patient.
In March 2019, the company halted companion studies that produced different results after an independent "futility analysis" concluded the drug did not seem to work. At the time, it appeared to join a growing list of amyloid-targeting drugs over the past two decades that looked promising in early studies only to fizzle in late-stage, expensive trials.
But after reviewing data from the two trials, Biogen decided there was enough evidence from one trial with positive results and signals from a subgroup of the second trial to support high doses of the drug as safe and effective. The company held talks with the FDA and submitted a new drug application, which the agency fast-tracked with priority review.
Dr. Howard Fillit, founding executive director and chief science officer at the Alzheimer’s Drug Discovery Foundation, said the FDA struck the right balance of giving patients access to a drug while requiring ongoing monitoring through a post-approval study. Had the FDA mandated another clinical trial before approval, it would have taken three to five years and a significant investment Biogen might not be willing to underwrite.
"Part of the target is for people who have a serious disease that is ultimately fatal," Fillit said. "Finally, the FDA is recognizing that Alzheimer’s disease is a serious disease. Right now, there are no survivors from Alzheimer’s disease."
Ken Alltucker is on Twitter at @kalltucker, or can be emailed at alltuck@usatoday.com
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