A panel at AMCP 2025 explored the successes and challenges of the US Food and Drug Administration’s (FDA) Accelerated Approval Program, stakeholder perspectives on access and management strategies, and innovative payment models, including a health plan’s approach to managing accelerated approval drugs for self-funded groups.

“Today, we want to focus on alternative pathways and drug development designations that are novel,” said Sneha Sharma, PharmD, director of specialty clinical solutions at Prime Therapeutics.

Dr Sharma provided an overview of expedited pathways designed to bring therapies to market faster. Fast Track accelerates the development and review of drugs for serious conditions with unmet needs. Breakthrough Therapy designation expedites development for therapies demonstrating substantial improvement over existing treatments. Priority Review shortens the FDA’s action timeline to 6 months. Expanded Access, or Compassionate Care, allows patients to receive non-FDA–approved therapies when no clinical trial is available, under physician request and Institutional Review Board (IRB) oversight. Accelerated Approval provides conditional approval for serious conditions based on surrogate endpoints, with a confirmatory trial required after market entry.

Traditional approval pathways rely on clinical endpoints like overall survival, baseline changes, and symptom improvement, often requiring 2 phase 3 trials and up to 17 years for full approval. In contrast, accelerated pathways use surrogate endpoints such as lab measurements or imaging, offering earlier access but requiring post-market confirmatory studies.

The Accelerated Approval Program, initiated in 1992 during the HIV epidemic, was designed to address urgent medical needs. In 2012, Congress passed the FDA Safety Innovations Act, allowing for expanded use of surrogate endpoints. By December 31, 2024, the program had resulted in 328 drug and indication approvals. Draft guidance released in December 2024 aims to strengthen oversight, requiring earlier confirmatory trials and enhancing communication between sponsors and the FDA.

The program has made a measurable impact: therapies have reached patients a median of 3.2 years earlier than through traditional pathways. An estimated 66% of accelerated approval drugs might not have otherwise reached the market. Notably, 2 therapies for non–small cell lung cancer (NSCLC) provided earlier access to over 500 000 patients and resulted in nearly 200 000 additional years of life.

However, challenges remain. Only 56% of drugs or indications approved via the accelerated pathway have received full approval. The time from application to approval has ranged from 2.5 to 28.7 months, while withdrawals have occurred between 1 and 6 years after approval. Oncology dominates the landscape, accounting for 69% of ongoing trials and 58% of converted approvals, followed by rare diseases, vaccines, and infectious diseases.

“As pharmacists, what is our role?” asked Dr Sharma. “Ideally, we want to see all of these drugs receive traditional approval after they’ve gained conditional approval. But we know the pathway is winding, so we have to educate providers and patients that these drugs are still under ongoing monitoring.”

Dr Sharma illustrated potential risks by highlighting 2 notable withdrawals: hydroxyprogesterone caproate (Makena), approved in 2011 and withdrawn in 2023 after failing to reduce spontaneous preterm births, and Melphalan flufenamide (Pepaxto), approved in 2021 and withdrawn in 2024 after not meeting its primary endpoint for multiple myeloma.

She also shared the story of Michael, a 15-year-old diagnosed with acute lymphoblastic leukemia in 2013, who was treated with clofarabine (Clolar)—a drug granted accelerated approval in 2004. Clofarabine’s initial trials included only 66 pediatric patients, with a one-third response rate. The FDA later acknowledged that clofarabine lacked a realistic chance of demonstrating clinical benefit without new studies, though it was eventually granted full approval in 2022.

"If we hadn't done [the clofarabine], we might have been able to get some more time out of him," Michael’s mother said. "But ... I think then I would be kicking myself for not doing the clofarabine and giving it a try. It's just kind of this big, ugly circle that no one wants to be in because [you're] damned if you do, damned if you don’t.”

New safeguards proposed in the FDA’s 2024 draft guidance aim to tighten the program. These include stricter criteria for surrogate endpoints, mandatory initiation of confirmatory trials before approval, regular progress reports to the FDA, and clarified, streamlined withdrawal procedures to expedite the removal of ineffective drugs from the market.

Patients and providers can access support and resources through groups like the FDA Innovation Hub, the Reagan-Udall Foundation, the Alliance for Patient Access, Friends of Cancer Research, and the National Organization for Rare Diseases (NORD).

“There have been 328 drug-indication pairs approved in the past 33 years,” noted Soumya Vishwanath, PharmD, formulary management director at Prime Therapeutics. She emphasized the significant rise in oncology approvals over the past decade. “With the number of accelerated approvals increasing, it is important for health plans and payers to understand how to manage these products.”

Dr Vishwanath outlined a 3-stage approach for formulary review: clinical review, policy decisions and implementation, and quality review. She highlighted challenges such as evaluating limited early data, managing rising costs, and navigating varying coverage approaches, especially between oncology and non-oncology treatments. Many plans implement temporary coverage blocks to allow time for more clinical evidence to emerge before making long-term coverage decisions.

The session also addressed broader system-wide implications. Confirmatory trials are often delayed, leaving many drugs on the market for extended periods without full approval. Dr Vishwanath stressed the growing concerns about the financial burden of later-withdrawn drugs and emphasized the need for a stronger, more transparent monitoring framework.

“Employers are increasingly asking how health plans are managing accelerated approval drugs, especially after high-profile drug withdrawals that result in wasted costs and limited patient benefit,” said Timothy O’Shea, MS, PharmD, director of specialty pharmacy at Horizon Blue Cross Blue Shield of New Jersey.

Dr O’Shea explained that employer groups and health plans are rethinking their management strategies, weighing full coverage, selective coverage, or complete exclusion of accelerated approval drugs. However, he argued that complete exclusion may be unethical, given the unmet medical needs these drugs address. Instead, he proposed a fourth option: developing warranty or outcome-based contracts between payers and pharmaceutical manufacturers to share financial risk while maintaining patient access.

He concluded by emphasizing that while the Accelerated Approval Program is critical for fostering innovation, it must evolve with stronger safeguards to ensure clinical effectiveness, patient safety, and responsible health care spending.

Reference 
O’Shea T, Sharma S, Vishwanath S. Education Session: [R5] Accelerated Approvals, Where Are We Now? A Follow Up on The Advantages and Pitfalls. Presented at: AMCP 2025; March 31-April 3; Houston, TX.