There are serious health conditions in which a new solution could fill a big unmet need. In that context, the FDA’s Accelerated Approval Program allows for the earlier approval of drugs on the basis of surrogate endpoints, among other things. A surrogate is thought to predict clinical benefit but is not a measure of actual clinical benefit. Think of the difference between correlation and causation; a surrogate for disease may be seen in people with a particular condition, but a positive surrogate outcome may or may not translate into a clinical benefit for them.
Case in point: The brains of patients with Alzheimer’s disease often have an accumulation of plaques containing beta amyloid. But that does not necessarily mean drugs that reduce amyloid will slow cognitive decline in patients with Alzheimer’s. Not only do payers know this, but they agree with separate assessments by an FDA advisory committee and ICER that there is insufficient evidence of a clinical benefit for Aduhelm. Yet to payers’ dismay, the FDA approved the amyloid beta-directed antibody on June 7 under its accelerated approval program, solely on the basis of plaque reduction.
When payers reject products the FDA approves, they have a few options.
Watchful waiting
With regard to controversial coverage decisions, there is a last-mover advantage. Between launch and review, many payers will use an NDC block and not cover the product unless an exception is granted. Such exceptions typically require trying and failing alternative therapies. With Aduhelm, most payers will likely delay their initial reviews. Even after an initial review, some may use interim policies to bide time before implementing formal policies.
For safety reasons, some payers routinely require a step through other covered products before members can access a new agent during the first year. During this first year, payers will monitor safety, and while it is unlikely that evidence of a clinical benefit will emerge in the short term, the emergence of swelling or bleeding events may heighten safety concerns and possibly lead to a REMS program.
Payers will also monitor other payers. Because most patients with Alzheimer’s are covered by Medicare, payers will closely monitor CMS coverage decisions. Medicare coverage is limited to products and services it deems “reasonable and necessary.” National coverage determinations (NCDs), like FDA approvals, are meant to be evidence-based processes. Given the controversial nature of Aduhelm’s approval and the large potential impact on Medicare, an NCD is likely. Whereas Medicare NCDs for drugs typically mirror FDA approvals, some NCDs have been more restrictive — specifying prior authorization (PA) and reauthorization criteria or requiring step therapy. CMS severely restricted coverage of Amyvid because of insufficient evidence of a benefit for diagnosing Alzheimer’s. Payers hope that Aduhelm suffers a similar fate.
Restricting access
Most payers covering Aduhelm will likely do so with restrictions. PA and reauthorization criteria will likely borrow the inclusion and exclusion criteria used in the clinical trials. PA criteria may limit use to patients with mild cognitive impairment or higher-than-normal levels of amyloid in their brains, established through a positive amyloid PET scan (which, paradoxically, some payers do not currently cover). In addition to stringent PA criteria, payers may also require a step through one or more covered medications that treat symptoms of Alzheimer’s. Payers covering Aduhelm are also likely to require routine MRIs for safety reasons. While routine monitoring adds to the cost of treatment, the burden of monitoring on patients could contribute to nonadherence and patient discontinuation, grounds for denying reauthorization.
By the way, an interesting theoretical Catch-22 would be if some of the large payers that currently do not cover amyloid PET scans — notably, Medicare — were to require such a scan for Aduhelm coverage. However, the ethical issues and negative PR of that approach would not be as clean as a more equitable decision to simply not cover Aduhelm. To avoid additional backlash, payers currently not covering amyloid PET scans but requiring such a scan for Aduhelm coverage would begin to cover such scans.
Contracting in exchange for access
Biogen CEO Michel Vounatsos says Aduhelm’s $56,000 annual list price “reflects the overall value this treatment brings to patients, caregivers and society.” (Well, not according to ICER, which pegged a fair price for Aduhelm at less than half of that in even the most optimistic scenario.) In the same statement, Vounatsos promised not to increase Aduhelm’s price for four years, an unusual preemptive move. Payers will likely want that written into contracts, and will wisely ask for additional years of price protection. Biogen also pledged to enter into value-based contracts with payers. But unless payers are convinced that the savings would likely exceed the costs, they won’t enter into such agreements. The lack of evidence of a clinical benefit makes the likelihood of Biogen committing to an outcome that would resonate with payers infinitesimally small. Deep discounts and/or large rebates in exchange for access are a much more likely scenario.
Blocking access
Then there’s the nuclear option — not covering Aduhelm at all. Given Aduhelm’s lack of evidence of a clinical benefit and its cost, all payers would like to block access to it. In some states and in the Federal Employee Health Benefits Program, however, this is not an option because these payers are required to cover an FDA-approved therapy when no covered alternative exists for that indication. Self-insured employers unwilling or unable to absorb the additional cost and/or raise premiums will block access. But the same political pressure that surely contributed to FDA approval may be too great for most payers to resist, unless CMS or another influential payer blocks access, giving other payers de facto permission to do so.
Because the FDA abdicated its regulatory responsibility to not approve Aduhelm, payers are the regulator of last resort. Perhaps there is a brave, influential payer willing to make a bold first move and block access. If so, other payers would surely follow this leader. Otherwise, suboptimally managed utilization and the resulting real-world evidence may make this the most expensive “trial” in history.
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