The cost of aducanumab

When donepezil (Aricept) was approved in 1996, it was the first tolerable drug available to treat the cognitive symptoms of Alzheimer’s disease. I remember being shocked that the price was so high, about $120 per month. Donepezil or two similar acetylcholinesterases, rivastigmine and galantamine, are still used by patients with Alzheimer’s disease.  I have been taking donepezil myself for over three years. Donepezil and its cousins appear to work by increasing the concentration of a neurotransmitter called acetylcholine in the nucleus basalis of Meynert, a region of the forebrain usually damaged by Alzheimer’s.  These drugs do not reverse or even slow the progression of the disease, but they often, though not always, provide a boost in cognitive abilities, at least for a few years. Since the FDA approval twenty-five years ago, the price of generic donepezil is now $185 per month, $30 LESS than the inflation adjusted cost of $205.  That’s right. Donepezil now costs less than brand name Aricept did in 1996 because now there is competition from generic equivalents.

As we have discussed in two previous posts, aducanumab, branded as Aduhelm, has just been approved by the FDA for treatment of any patient with Alzheimer’s disease, even those in the late stages for which it has not been tested and for which it is unlikely to be effective and in whom side effects may be worse. In early-stage Alzheimer’s, aducanumab is effective at removing amyloid, but effects at slowing cognitive decline were mixed, and there is no evidence that it improves cognition unlike the acetylcholinesterase inhibitors that at least temporarily cause noticeable improvement in cognitive function in many Alzheimer’s patients.  Yes, aducanumab is the first approved disease-modifying drug.  But the data so far show only a modest cognitive benefit on a par (to be generous) with drugs like donepezil that have been around for 25 years and cost $185 per month.  Biogen, the maker of aducanumab, plans to charge $56,000 per year, or $4,667 per month for a drug that thus far has not been proven to be as effective on cognitive loss than drugs costing only 4% as much. Aducanumab may well be better, but we need further studies to better define its effectiveness and ultimate value.

As described in the New York Times last week, the cost of aducanumab as priced could bankrupt Medicare as well as Medicare patients without supplemental drug insurance. While the Alzheimer’s Association supports the approval of aducanumab, it objects to the high cost. “This price is simply unacceptable. For many, this price will pose an insurmountable barrier to access, it complicates and jeopardizes sustainable access to this treatment, and may further deepen issues of health equity. We call on Biogen to change this price.”  A pricing analysis conducted by the Institute for Clinical and Economic Review (ICER) concluded, “although ICER’s preliminary judgment is that substantial uncertainty remains regarding the health benefits of aducanumab, a base-case cost-effectiveness analysis was performed using the combined results from the two contradictory phase III randomized trials. Results showed estimates of small overall health gains commensurate with value-based prices at traditional cost-effectiveness thresholds between $2,500-$8,300 per year.”  In short, a more realistic price for this drug given the uncertainty of its effectiveness would be about $5,000 per year, about 10% of what Biogen wants to charge. As shown in the figure at the top from the New York Times, the cost to the national budget for aducanumab priced at $56,000 per year could be greater than the budget of NASA, the National Science Foundation, and the CDC. All this for a drug that has yet been proven to be effective. Really?