5:10 a.m. - 2021-09-10
ADUHELM
Aducanumab (trade name Aduhelm, by Biogen) is a monoclonal antibody given by intravenous infusion to treat Alzheimers Disease. Although heralded with enthusiasm by the Alzheimers Association, its recent approval by the FDA is not without controversy. Critics believe the decision was driven in part by the tragic magnitude of unmet needs, and fear that desperation to find a treatment in the face of so much suffering led the FDA to lower its standards.

In seeking FDA approval for the drug, Biogen performed two studies, but only one showed possible positive outcomes. Beta amyloid is a protein that forms plaque--hard, insoluble deposits--in the neurons of Alzheimers patients that is thought to contribute to cognitive decline. In one of the studies, PET imaging showed a dose-related decline in beta amyloid in the brain, and patients receiving high doses showed a 22% lower decline in cognitive function at eighteen months, compared to placebo. Cognitive decline did not cease, however, and was not reversed. The observed slowing of cognitive decline occurred only in patients with moderate symptoms. Temporary swelling of the brain and mild bleeding was reported in 30% of patients.

Since other Alzheimers studies have shown a lowering of amyloid without a corresponding increase in cognition, there is no convincing evidence that amyloid is a valid surrogate for mental impairment. During the evaluation period, the FDA's Peripheral and Central Nervous System Advisory Committee counseled against approval, and three members resigned in protest at the FDA's action. Biogen will need post approval trials to prove clinical benefits (as opposed to simply lowering amyloid); these trials would go until 2030 while sale of Aduhelm went forward at profit to Biogen. Further criticism takes note of the fact that the drug was approved for all patients despite showing promise only in cases of mild impairment. Aduhelm was not tested in patients taking blood thinners, and--despite the bleeding cases cited above--there are no warnings or contraindications listed for this patient population.

A further concern is the price of Aduhelm: $56000 for one year of therapy, which is only the drug cost and does not include infusion equipment, the time of medical personnel, and possible tests and procedures that may be mandated by insurance companies. Most Alzheimers patients are elderly, so most of the cost would be borne by Medicare. Patients using Medicare Part B, which pays 80% of medical cost, could have copays as high as $11,500, while the mean annual income for Medicare patients is only $29,650. If only a quarter of eligible patients used Aduhelm, the cost to Medicare would be $29 Billion annually, making it far and away the single most expensive drug in the United States.

Aside from the financial drain on Medicare, critics believe the drug to be overpriced for its likely value in therapy, arguing that only a hypothetical drug that halted Alzheimers entirely would be worth the $56000 annual price tag. Other Alzheimers drugs currently on the market are considerably less expensive. Aricept, and acetylcholinesterase inhibitor, costs $6420 per year, while Namenda, a glutamate regulator, is priced at $5688.

Alzheimers is a tragic disease, causing suffering and despair for entire families. But a questionable therapy with a high price tag, applied across the board and without caveats, is not the answer.

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