In June 2021, the Food and Drug Administration (FDA) approved the Alzheimer’s drug Aduhelm through the agency’s Accelerated Approval Program. This pathway allows for earlier approval of drugs that offer a meaningful benefit over existing therapies and treat serious conditions that have an unmet medical need. Controversy surrounding Aduhelm’s extremely high cost, along with questions over its clinical benefit and health risks to patients, has placed the accelerated approval pathway under scrutiny.
How does the accelerated approval pathway work?
Established in 1992 in response to the HIV/AIDS crisis, the accelerated approval pathway allows the FDA to speed approval of drugs based on a “surrogate endpoint” rather than a direct measure of clinical benefit, as required for traditional FDA approval. Surrogate endpoints are substitute measures that are either known or likely to predict clinical benefit but do not directly measure clinical benefit. For example, the benefit of a drug submitted for accelerated approval might be determined through laboratory measurements or radiographic imaging rather than its ability to prolong life. Once approved via the accelerated approval pathway, the manufacturer must study the drug further to confirm its clinical benefit. If these postapproval conditions aren’t met, the FDA can withdraw its approval.
What are the controversies surrounding accelerated approval?
Postapproval confirmatory trials are often delayed; in some cases, they can take more than a decade to complete. Moreover, some drugs granted accelerated approval have later been proven ineffective or unsafe for patients, sometimes after being on the market for years.
Critics also point to the high cost of drugs approved via the accelerated approval pathway (like Aduhelm) — costs that the government, private payers, and consumers bear without clear evidence of patient benefit.
What reforms have been proposed to the FDA’s Accelerated Approval Program?
Some policy proposals argue that pharmaceutical companies should have a limited time to conduct postapproval trials to prove a product’s clinical benefit. They also say the FDA needs clear guidelines for how and when the agency can remove a drug from the market if companies don’t conduct confirmatory trials in a timely manner, or if findings from a trial indicate poor safety or effectiveness.
The FDA released a set of legislative proposals asking Congress for authority to ensure that drug sponsors develop postapproval studies that are adequately designed and can be completed in a timely manner.
Measures to reform accelerated approval have emerged from the House of Representatives’ Energy and Commerce Committee and the Senate’s Committee on Health, Education, Labor, and Pensions as part of legislative packages centered on the FDA’s prescription drug user fees. Both the House and Senate bills would require the FDA and drug manufacturers to agree on postapproval study conditions prior to a drug’s approval and require more regular study progress updates from manufacturers. The proposals also would permit the FDA to require studies to be underway at the time the drug is approved, or prior to that time, and allow use of real-world evidence to support the studies.
The FDA already has the ability to withdraw a drug’s accelerated approval when postapproval studies are not conducted with due diligence, if clinical benefit is not verified, if the product is proven unsafe or ineffective, or if a drug sponsor disseminates false or misleading promotional materials. However, both the House and Senate measures streamline the FDA’s procedures for expediting the withdrawal of a drug’s approval in the event it becomes necessary to do so.
Both bills also would establish a pilot program allowing the FDA to collaborate more closely with sponsors of drug development programs that target rare diseases in order to “[advance] the development of efficacy endpoints, including surrogate and intermediate endpoints.”
Neither bill included a provision put forward by Rep. Frank Pallone (D–N.J.) to allow, with certain exceptions, the automatic expiration of a drug’s accelerated approval “one year after [the] target date of study completion, and in no case later than five years after the date on which the product [was] approved.”
While the House and Senate proposals are similar, one difference is the Senate bill’s establishment of an intra-agency coordinating council within the FDA “to ensure the consistent and appropriate use of accelerated approval.” Among other tasks, the council would be responsible for developing guidance for FDA staff and best practices for the review of accelerated approval products.
What about insurance coverage and reimbursement for accelerated approval drugs?
State Medicaid officials are also considering their options to address the growing cost of accelerated approval drugs. For example, Oregon has requested permission to exclude coverage of accelerated approval drugs that lack evidence of clinical efficacy, arguing that such authority might encourage drug sponsors to move more quickly to complete postapproval trials.
Additionally, the Medicaid and CHIP Payment and Access Commission last year provided recommendations to Congress to “strike a balance between addressing state concerns . . . while maintaining access for beneficiaries.” One recommendation for incentivizing drugmakers to complete their confirmatory trials quickly is to increase the monetary rebates they pay under the Medicaid program until such studies are complete.
Other proposals, including those put forth by the Institute for Clinical and Economic Review, seek to address the high cost of accelerated approval drugs by tying coverage to patient benefit and the presence of an outcomes-based contract, or by creating a new “safety only” approval pathway that would not require public or private insurers to pay for approved treatments.
What happens now?
It appears increasingly likely that Congress will pass reforms to the accelerated approval pathway as part of the legislation around prescription drug user fee reauthorization. These reforms are likely to increase pressure on drug companies to conduct postapproval trials in a timely fashion. They will also potentially give payers cover to restrict coverage when a drug fails to prove its efficacy, as UnitedHealthcare did for Aduhelm.
However, as state and federal governments continue to struggle with the growing costs of accelerated approval drugs, Congress is likely to face continued calls for more significant reforms.
