Learning from Aduhelm

How the Aduhelm controversy could spark needed reforms in regulation and reimbursement

Every participant in the Aduhelm debacle can point to ways in which other players have failed Alzheimer’s patients and their families. Now that CMS has released its final coverage decision, it is time to move from finger-pointing and doom-casting to learning from the experience and collaborating to put reforms in place that will increase the chances the system works better in the future.

Rather than continue to debate the merits of decisions FDA and CMS have made about Aduhelm, patients with dire diseases such as Alzheimer’s would be better served if the key players in the biomedical ecosystem came together to make the path to approval more efficient and predictable, and moved toward creating a learning healthcare system and adaptive payment systems.

The experience with Aduhelm has spotlighted longstanding problems:

· FDA’s idiosyncratic, inconsistent decision-making, lack of transparency about approval standards, and apparent tolerance of “back channel” communications between regulators and product developers

· The tendency of some biopharma companies to bet that urgent medical needs will lead FDA to overlook the absence of compelling data and force payers to swallow unjustified prices

· The failure of many patient groups to ensure both the reality and the appearance of independence from drug companies that fund their advocacy

· An inflexible coverage and payment system that is incapable of making nuanced decisions linking reimbursement to value, and the inability of the healthcare system to generate accurate outcomes data that could inform clinical decisions, product development and payment

FDA should create an open, transparent process for soliciting scientific advice about pathways to approval, including surrogate endpoints for accelerated approval. It should announce requirements in advance of making product approval decisions and, in the absence of a clear public health rationale, inform the public before changing them.

In Aduhelm’s case, FDA said in a 2018 draft guidance that “the effects on biomarkers in AD are not sufficiently well understood to provide evidence of a persistent effect on disease course,” and it told the Aduhelm advisory committee that accelerated approval wasn’t being considered. 

The controversy raised by FDA’s decision to disregard its advisory committee’s recommendation against approving Aduhelm, and CMS’s highly restrictive coverage decision, based on a repudiation of basing approvals on reductions in β-amyloid deposits, illustrate the negative consequences of failing to achieve consensus about, or at least publicly justify the use of, a surrogate endpoint.

Public workshops to discuss and debate approval criteria for a disease or class of therapies would be more valuable than the current practice of seeking advice from advisory committee meetings that are typically scheduled when a PDUFA goal is in sight. Advisory committee meetings are often held too late in the development process, the committees don’t have the right people, and FDA asks them the wrong questions. Most advisory committee members lack expertise that is relevant to the product under consideration, and FDA often asks the committee for recommendations about complex regulatory issues that they are unqualified to provide.

The Aduhelm experience points to the need for FDA, patients and Congress to engage in discussions about accelerated approval. Goals could include refining vague standards such as “reasonably likely to predict clinical benefit,” establishing benchmarks for how much risk the agency should take in exchange for getting drugs to patients faster, and creating policies to ensure that post-approval evidence is generated rapidly.

Such discussions would likely lead FDA to return to the notion it once held that accelerated approval is not intended to compensate for failed clinical trials.

The Aduhelm experience also highlights the importance of coupling scientific and regulatory innovation with innovative coverage and payment policies. While combatants on both sides of the Aduhelm wars say they are fighting about scientific truth and the health of Alzheimer’s patients, the battles would have been far more subdued if the drug had been priced more modestly.

In BioCentury’s Back to School package last fall, which explored ways to modernize the accelerated approval pathway, former CMS Administrator Mark McClellan advocated creating a system in which manufacturers can share the uncertainty about drugs that receive accelerated approval. Under this idea, Aduhelm could have been launched at a price far lower than the $56,000 per year Biogen Inc. (NASDAQ:BIIB) initially asked; the company would have been able to increase the price if and when evidence robustly demonstrating its utility was produced. Such a system would incentivize rapid collection of confirmatory data.

This kind of adaptive pricing would require changes in the way “best price” is calculated for Medicaid. More fundamentally, it could work only if healthcare delivery and IT systems were modernized to make it possible to consistently track outcomes for individual patients or populations. The absence of outcomes data prevents healthcare from achieving the kind of continuous improvement that is routine in many other sectors. Creating systems for tracking outcomes is a goal that would benefit every participant involved in developing and using therapies, from patients to payers. It is a task that could bring together patient advocates, academic scientists, drug company researchers, private insurance companies, government payers and more. 

These ideas are only the beginning of the kind of progress that could be achieved if the focus shifts from assigning blame to learning and applying lessons from Aduhelm.

Signed commentaries do not necessarily reflect the views of BioCentury.