For the first time in 18 years, the FDA has approved a drug to treat patients with Alzheimer’s disease. It’s great news for the millions of Americans, and their family members, who are fighting this terrible disease. But all the news was not great.
The approval did not come without controversy. The fact that three of the 11 members of the FDA’s neurological drugs advisory panel resigned in the wake of the approval of Biogen’s Aduhelm attests to that. And not one of those 11 people voted to approve the drug, with 10 voting no and one “uncertain”. In addition, a recently released internal memo revealed the FDA approved this drug despite objections from the FDA’s statistics office. The statisticians felt the clinical trial data fell short of the proof typically required to approve a drug.
The FDA signed off on Aduhelm using the Accelerated Approval pathway, which is utilized when a drug for a serious or life-threatening illness may provide better results than existing treatments despite uncertainty about the clinical benefit. While the approval of the drug brings with it questions about cost, efficacy and side effects, it also brings hope.
Aduhelm is a Breakthrough
Alduhelm is a monoclonal antibody administered as a once-monthly intravenous infusion. According to the FDA, Aduhelm is “the first treatment directed at the underlying pathophysiology of Alzheimer’s disease, the presence of amyloid beta plaques in the brain.” That’s the most exciting, and encouraging, aspect of this drug. All other Alzheimer’s treatments target symptoms and not the underlying disease.
The long-overdue optimism that arrived along with Aduhelm still needs to be tempered. The skids of approval were greased by time. Eighteen years is an eternity to wait for reinforcements to help battle a disease that affects so many.
The hope is still real. Aduhelm doesn’t stop Alzheimer’s or improve a patient’s condition. But, if it works, it slows down the process. It will give people more time. It will give families more time. For so long it’s been nothing. This is something.
Did You Say ‘If it Works’?
The studies on Aduhelm are conflicting, including conclusions that found either zero or slight efficacy. The FDA decided to approve Aduhelm based on a surrogate endpoint instead of actual clinical benefit in improved cognition. While the specific causes of Alzheimer’s disease are not fully known, this disease is characterized by high levels of amyloid beta plaques in the brain. The more of the chemical that accumulates in the brain, the worse the condition for the patient. Aduhelm lowers those levels. However, it’s still not clear whether reducing amyloid plaque correlates to slowing the decline of cognitive function in Alzheimer’s patients. One of the requirements of this drug, because it was a fast-track approval, is to continue the ongoing studies to prove its efficacy.
Potentially serious side effects are also concerning. Amyloid-related imaging abnormalities-edema (ARIA-E), which is edema of the brain, may occur. ARIA-hemosiderin deposition is another type of ARIA which is associated with hemorrhages in the brain.
The Cost Will Be Significant
The price tag on Aduhelm is steep, with estimates landing around $56,000 a year for an average weight patient. It’s not outrageous when compared to the cost of certain biotech drugs, like in oncology, but with over 6.2 million people afflicted with Alzheimer’s, that number adds up quickly.
Since Alzheimer’s most commonly affects the elderly, a vast number of Alzheimer’s patients are on Medicare, but even with the questionable efficacy of Aduhelm it would be hard to imagine CMS not approving a drug that was FDA approved. The effect could still be felt by the commercial health plans as well, with out-of-pocket costs possibly reaching $10,000 annually.
Site of service will also play a factor in the cost. The price of a monthly infusion at a doctor’s office, an outpatient center and a hospital are not the same.
Alduhelm is approved for the treatment of Alzheimer’s disease. This is the broadest label the FDA could have approved. It would be prudent for employer groups and payers to consider utilization management opportunities to help assure the appropriate patient is getting the medication. Physical and neurological exams along with cognitive testing are paramount in diagnosing Alzheimer’s. Although every patient in the clinical trials received PET scans to confirm elevated brain amyloid levels, this is not part of the label, nor is it generally paid for by Medicare. PET scans or CSF (cerebrospinal fluid) testing to identify amyloid deposition may be a prudent requirement; however, PET scans are expensive and are not covered by Medicare and lumbar punctures to obtain CSF are not without risks. These are just some of the considerations when coming up with prior authorization criteria.
The Ripple Effect
It’s reasonable to assume that the approval of Aduhelm may make it easier for other drugs with questionable statistics to get approval down the line. The FDA signing off on a drug with this diminished level of evidence could certainly lower the bar and open the door for others. Containing this ripple before it gets out of hand is probably in everyone’s best interest.
One question that still remains for the FDA is why even have an expert panel whose opinions can be so universally ignored and overruled. The FDA is dealing with the fallout where available evidence on the clinical endpoints is short of what is normal evidence required for the standard approval of Alduhelm. Critics say the FDA ignored scientific standards it typically holds drug makers to which may result in the federal government spending billions on a drug that may not work.
Who has access to the drug in the near future will depend largely on the next move by CMS. And speaking of monitoring, employer groups and payers are watching closely before making their own determinations on how to move forward.