FDA Taking a Big Gamble on Alzheimer’s Drug; Expect Payers to be Wary [at Best]

It is difficult to speculate on what FDA’s motivation might be to overrule the recommendation of its Advisory Committee and approve Biogen’s aducanumab for the treatment of mild Alzheimer’s disease. Relatively few providers are convinced of the value of this agent based on the clinical trial results reviewed, and many are outspoken in their opposition to it. Based on the providers’ perspective, what are payers supposed to think?

Research in the Alzheimer disease category has resulted in depressingly few bright spots. Biogen’s agent does not seem to break any new ground here—a drug that helps clear amyloid plaque from the brain seems to achieve that goal, but without showing meaningful differences in cognitive improvement (or delayed progression). The clinical trials proved this. FDA seems to be holding out hope that this mechanism of action will be proven beneficial at some point in the future. Certainly, they do not have this evidence to date. The fact that the approval will require a phase 4 clinical trial to support this hope is frankly uninspiring. Newly diagnosed patients will clamor for the drug, despite its poor record of efficacy and its significant risks, placing providers and payers in a difficult bind.

Alzheimer’s disease is a disorder heavily weighted toward the elderly population, and Medicare will be expected to bear the brunt of the bill for aducanumab. Early estimates have gone as high as $10 billion annually based on the prevalence and incidence of Alzheimer’s disease. This points to the immediate need for a national coverage determination (NCD) to help guide Medicare coverage. Health policy experts are calling for this to begin now. However, commercial payers will also need to make coverage policies pertaining to the agent.

In other words, payers will have their hands full trying to measure value against the projected $56,000 yearly cost of treatment. In an earlier analysis, ICER revealed that aducanumab may not be cost effective at one-tenth this price. Reacting to the approval, ICER sent out its own commentary, taking the FDA to task.

Payers, including Medicare Advantage plans, can utilize prior authorization criteria and step edits to manage appropriate access to this treatment. In this case, “appropriate access” may be very difficult to define, outside of an investigational clinical trial. Ordinarily, when products are approved by the Food and Drug Administration, there is an expectation of careful evaluation and decision making based on the efficacy and safety of the medication. In an accelerated approval scenario such as this, this expectation is not met. Judging from the cacophony of confusion coming from neurologists on this decision, I don’t believe that we have a clear understanding of whom this agent may benefit. Maybe it is just wishful thinking from the FDA that clearing amyloid plaque will somehow equate to better cognitive function (perhaps in a smaller subset of patients). Until we have real evidence that this is the case, a very conservative approach seems warranted. Let Biogen conduct the new study and prove the concept works. Until then, the number needed to treat, and the cost of that treatment, to gain benefit in one patient could indeed be enormous.

Research in the Alzheimer disease category has resulted in depressingly few bright spots. Biogen’s agent does not seem to break any new ground here—a drug that helps clear amyloid plaque from the brain seems to achieve that goal, but without showing meaningful differences in cognitive improvement (or delayed progression). The clinical trials proved this. FDA seems to be holding out hope that this mechanism of action will be proven beneficial at some point in the future. Certainly, they do not have this evidence to date. The fact that the approval will require a phase 4 clinical trial to support this hope is frankly uninspiring. Newly diagnosed patients will clamor for the drug, despite its poor record of efficacy and its significant risks, placing providers and payers in a difficult bind.

Alzheimer’s disease is a disorder heavily weighted toward the elderly population, and Medicare will be expected to bear the brunt of the bill for aducanumab. Early estimates have gone as high as $10 billion annually based on the prevalence and incidence of Alzheimer’s disease. This points to the immediate need for a national coverage determination (NCD) to help guide Medicare coverage. Health policy experts are calling for this to begin now. However, commercial payers will also need to make coverage policies pertaining to the agent.

In other words, payers will have their hands full trying to measure value against the projected $56,000 yearly cost of treatment. In an earlier analysis, ICER revealed that aducanumab may not be cost effective at one-tenth this price. Reacting to the approval, ICER sent out its own commentary, taking the FDA to task.

Payers, including Medicare Advantage plans, can utilize prior authorization criteria and step edits to manage appropriate access to this treatment. In this case, “appropriate access” may be very difficult to define, outside of an investigational clinical trial. Ordinarily, when products are approved by the Food and Drug Administration, there is an expectation of careful evaluation and decision making based on the efficacy and safety of the medication. In an accelerated approval scenario such as this, this expectation is not met. Judging from the cacophony of confusion coming from neurologists on this decision, I don’t believe that we have a clear understanding of whom this agent may benefit. Maybe it is just wishful thinking from the FDA that clearing amyloid plaque will somehow equate to better cognitive function (perhaps in a smaller subset of patients). Until we have real evidence that this is the case, a very conservative approach seems warranted. Let Biogen conduct the new study and prove the concept works. Until then, the number needed to treat, and the cost of that treatment, to gain benefit in one patient could indeed be enormous.