The accelerated approval pathway has transformed access to treatments for serious conditions since 1992. This FDA mechanism relies on surrogate endpoints reasonably likely to predict clinical benefit, followed by confirmatory trials. It has enabled early availability of therapies like pembrolizumab for cancers, saving an estimated 263,000 life-years by 2022. However, controversies around drugs such as aducanumab and Elevidys reveal ongoing tensions in evidence quality, pricing, and payer decisions. This article assesses recent reforms, therapeutic challenges, and policy steps to enhance the accelerated approval pathway for patients, payers, and innovators.

Historical Context and Recent Reforms

Lawmakers created the accelerated approval pathway amid the HIV/AIDS crisis to speed treatments via surrogate markers, such as viral load reductions. Today, about 200 drugs remain under this status, with oncology leading conversions to full approval in a median 3.2 years. FDORA (2022) mandated underway confirmatory trials and expedited withdrawals, prompting 25 oncology pullbacks since 2021—up from six before. FDA guidance now clarifies surrogate criteria and labels uncertainties directly.

Stakeholders welcome these shifts. For instance, time to full approval in oncology dropped from 4.3 years (pre-2014) to 2.3 years recently. Yet, 35% of trials once lagged schedules, costing Medicare $9.1 billion on non-converted oncology AAs in 2019 alone.

Challenges Across Therapeutic Areas

The accelerated approval pathway performs unevenly by disease type. In oncology, surrogates like progression-free survival (PFS) often fail to predict overall survival; one-third of 2013-2017 PFS-based approvals showed no gains. Rare diseases struggle with tiny populations—Barth Syndrome’s elamipretide faced multiple rejections before approval on muscle strength surrogates. Neurology contends with elusive biomarkers, as amyloid clearance in Alzheimer’s succeeded in just two of eight trials.

• Oncology: Maximum tolerated dose practices inflate toxicity without efficacy boosts.
• Rare diseases: Patient endpoints like ambulatory scores clash with trial power.
• Neurology: Slow progression demands novel biomarkers.

These variations demand tailored approaches to surrogates and trials.

Pricing, Access, and System Impacts

High costs exacerbate issues. Elevidys launched at $3.2 million; Medicare spent $224 million on withdrawn AA cancer indications (2017-2019). Payers restrict coverage—some delay AA drugs 18 months—causing delays in fatal conditions. Patients report financial toxicity, with nearly one-third skipping doses due to expense. Surveys show 60% distrust pharma and insurers alike, fuelling prior authorisation battles.

Policy Recommendations for Improvement

Targeted reforms can strengthen the pathway. First, refine surrogate selection through mandatory advisory committees, public hypotheses on clinical predictions, and patient input—learning from failures via after-action reports. Second, increase transparency with risk ratings (e.g., surrogate strength, delay predictors) and standardised decision explanations.

Third, align finances: enforce value-based pricing capping at expected outcomes; deploy outcomes-based contracts (OBCs) for high-uncertainty cases, centralised via CMS models; waive cost-sharing for no-alternative therapies. Finally, tailor oversight—expand oncology-style centres of excellence—and reserve AA for severe unmet needs (e.g., >5 life-year shortfalls), with auto-withdrawals for delays.

Combining these builds trust. OBCs, for example, could rebate 80% for non-responders, as in bluebird bio’s model.

Conclusion and Call to Action

Progress in the accelerated approval pathway—shorter timelines, firmer enforcement—signals viability, but trust deficits persist. Rigorous surrogates, transparent decisions, and value-aligned pricing will ensure benefits outweigh risks. Regulators, payers, and firms must collaborate to deliver affordable access.

Reference

https://icer.org/wp-content/uploads/2026/04/Strengthening-the-FDAs-Accelerated-Approval-Pathway-_-ICER-White-Paper-_-April-2026.pdf