Every Second Counts: the Impact of FDA’s Accelerated Approval Program

During the past 3 decades, the US Food and Drug Administration’s (FDA’s) Accelerated Approval Program (AAP) has saved and extended countless lives by enabling earlier market access to more than 280 life-changing medicines, many now considered standards of care. Despite this success, the program has come under scrutiny during the last few years, with critics stating it is not rigorous enough, has rapidly expanded, allows for too much uncertainty and risk, and, in a few instances, has led to the approval of ineffective drugs. Based on these concerns, critics have proposed changes to AAP policy to reduce its use or alter current processes.

In addition, for the first time, an insurance company recently issued a policy to restrict access to therapies that have received accelerated approval based on a surrogate endpoint for at least 18 months after FDA approval, excluding drugs to treat cancer or those for which coverage is required by federal or state regulations. The company cited these products’ lack of acknowledged clinical benefit, despite FDA approval, and stated the 18-month exclusion provides time to review emerging studies, data, and any additional clinical evidence supporting the drug’s safety and efficacy.

When considering changes—whether restrictions or expansions—to the FDA’s AAP policy and insurance coverage policies, the impact on patients should be the determining factor. However, no population-level impact of the program had been conducted to ground debates in actual evidence. To fill this evidence gap, Johnson & Johnson undertook a research project to understand the AAP’s impact at the population-health level in oncology. Without quantifying and understanding the impact, changes to AAP policy risks life years lost for millions of current and future patients.

What Is the Accelerated Approval Program?

The FDA instituted the AAP to allow for earlier approval of drugs that treat serious conditions and fill an unmet medical need. When reviewing drugs under the accelerated program, the FDA allows use of a surrogate endpoint, which is a marker, such as a laboratory measurement, radiographic image, physical sign, or other measure, that is thought to predict clinical benefit but is not itself a measure of clinical benefit. For example, the FDA can approve a treatment for cancer based on evidence that the drug shrinks tumors because the shrinkage is a predictor of the desired clinical outcome.

Use of a surrogate endpoint can shorten the time for a drug to come to market compared to traditional FDA approval. Drug companies are still required to conduct studies to confirm the anticipated clinical benefit and obtain traditional FDA approval. Further, the FDA may withdrawal the accelerated approval if confirmatory trials are not conducted or do not confirm the clinical benefit.

Quantifying the Impact of Earlier Access on Patients

Previous papers had reported on the successes and limitations of the AAP; however, analyses were limited to counts of successful approvals. Identifying an evidence gap for a population-level assessment of the AAP, Johnson & Johnson developed a first-of-its-kind model to determine the number of life years gained for cancer patients because of the earlier access enabled by the AAP.

Published in the Journal of the National Comprehensive Cancer Network (JNCCN) in April 2024, Johnson & Johnson research estimated that from 2006 to 2022, across 69 products for which overall survival data were available, approximately 911 000 cancer patients gained about 263 000 life years due to earlier access enabled by the AAP. This evidence shows that a substantial number of life years were gained for patients with high unmet need by the cancer therapies approved under the AAP.

Patient, Clinician, and FDA Support for the AAP

In November, 2024, Reuters Events held a webinar titled, The Future of the FDA Accelerated Approval Program on Outcomes for Patients. The event provided an opportunity for various stakeholders to voice their thoughts about the impact of the AAP.

For patients like Jenny Ahlstrom, a patient with multiple myeloma and CEO of HealthTree, the benefits of the AAP are undeniable. “I’m full of gratitude to FDA and these companies driving new innovation because I, and other patients I advise, have personally benefited,” Ahlstrom said during the webinar. “Since my diagnosis in 2010, we’ve really seen an explosion of new [multiple myeloma] therapies with now over 20 plus drugs being approved … and many of these coming through the Accelerated Approval Program.”

During the Reuters webinar, experts also discussed the latest research and the AAP in the context of key issues:

• Approvals under the AAP are as rigorous as traditional approvals: Criticism of the program has focused on concern that its approved treatments are “unconfirmed” and therefore possibly ineffective. As Peter Marks, MD, PhD, Director of the FDA’s Center for Biologics Evaluation and Research, explained, the AAP is as rigorous as the traditional approval pathway. “You have to have substantial evidence of effectiveness,” he said. “You can’t just say, ‘Oh, it kind of looks like it might work’… it is every bit an approval that meets our [FDA] standards.”

• Surrogate endpoints are appropriate outcomes: Approving therapies via surrogate clinical endpoints enables patients suffering from life-threatening diseases with great unmet need to receive potential life-changing therapies, on average, 3 years faster than traditional approval. It also encourages clinical research in disease areas that are extremely difficult to investigate. “Having a surrogate endpoint such as a biomarker that is reasonably likely to predict a clinical benefit can not only make a trial shorter, it allows all patients with that disease to start receiving it sooner. But it may be the factor that allows the trial to take place at all, because how else do you entice sponsors to work on such difficult projects,” said Edward Neilan, MD, PhD, Chief Science and Medical Officer for the National Organization for Rare Disorders (NORD).

• Withdrawals do not indicate a failure of the AAP: Following accelerated approval based on evidence using an approved surrogate endpoint in areas of high unmet need, a certain number of withdrawals are to be expected as data are collected on clinical outcomes. However, a withdrawal does not always indicate a failure of the treatment or the program itself. Dr. Marks commented, “I think that's really important to understand that sometimes a drug may work but the trial design was not able to demonstrate that it worked. In the oncology space I can think of one drug where the drug came off the market and was studied again and was found to actually work quite well in certain settings and is now back on the market.” He added that new processes pertaining to withdrawals will now enable the FDA to work more quickly if there is an issue. “If we make a decision now to withdraw a product, [withdrawals] could happen in a matter of months as opposed to years.”

FDA’s AAP Saves Time and Lives

In conclusion, policy discussions about the future of the AAP are not complete without assessing impact on its most important target outcomes to patients. Johnson & Johnson’s peer-reviewed study shows that the program benefits patients and helps them access much needed medications years sooner.

For patients and their families, those years matter. Even for patients who have benefited from the program, the fight is not done: “Myeloma patients are going to use every tool in the toolbox during their lifetime, and we need more tools. So, we need this innovation to continue,” Jenny Ahlstrom said during the webinar.

About Tom Valuck, MD, JD 

Tom Valuck, MD, JD, is a Partner at Real Chemistry. He is a thought leader on health care system transformation and helps lead the firm’s focus on achieving better health and health care outcomes at a lower cost. Tom’s work at Discern includes facilitating the exploration of next-generation measurement and accountability models for health care delivery systems. He also helps clients develop strategies to achieve success within the value-based marketplace.

About Bridget Doherty, MPH, MS

Bridget Doherty, MPH, MS, is the Director of Access and Policy Research at Johnson & Johnson Innovative Medicine, where she develops and executes impactful policy research and scientific engagement plans aimed at developing an evidence-based understanding of U.S. healthcare policies’ impact on patients and the healthcare ecosystem. One of her key contributions includes the first comprehensive analysis of the FDA Accelerated Approval Program's impact on patient outcomes. Bridget has published extensively on pivotal topics such as drug pricing policies and patient access, and she has led successful engagement strategies with advocacy and government relations partners.

About Silas Martin, MS

Silas Martin, MS is the Head of Access and Policy Research at Johnson & Johnson Innovative Medicine, where he leads a team of researchers focused on generating novel evidence and fostering external engagements with experts in economics and health policy in support of policies that enable patient access to transformational innovation now and in the future. In his tenure at J&J, Silas has led teams, and published research is the areas of health economics, outcomes research, market access and healthcare quality. He is an active partner to patient advocacy organizations, health systems, health plans, life-science industry coalitions, and academic groups.