A Look Back on AdComms in 2024, 5 Takeaways for 2025

BOLDAPPROVED Newsletter Issue 6:?A Look Back on AdComms in 2024, 5 Takeaways for 2025

We are kicking off 2025 with our top 5 takeaways from 2024 that sponsors should consider as they prepare submissions for approvals and potential AdComms in the new year.

AdComms provide a unique window into how FDA is tackling challenging regulatory issues and how they are using expert feedback from the Committee members. We have carefully evaluated every AdComm in 2024 with an eye towards what sponsors need to be thinking about so they can adapt and increase their chances of success.

Overview of AdComms in 2024

In 2024, there were 29 AdComms for drugs and biologics, which is close to the average number of AdComms held in the last 5 years. The AdComm year did not officially kick-off until March, and even then, it was a slow trickle of meetings through the middle of the year before finally picking up the pace leading into Q4, such that more than half of the AdComms occurred in the last 4 months of the year.

The majority of AdComms in 2024 (59%) involved sponsors and Committee voting/discussion with potential to directly impact subsequent FDA decisions. Out of the 29 AdComms, 14 involved the review of data submitted by a sponsor as part of a new drug application (NDA) or biologics license application (BLA) or a supplemental NDA or BLA (sNDA/sBLA) (“approval meetings”). Additionally, there were 3 multi-sponsor issue meetings this year which involved discussion of issues related to already approved/marketed drugs.

Our top 5 takeaways for sponsors focuses mainly on the 14 AdComms concerning new approvals.

1. FDA approval decisions are highly likely to align with the voting outcomes and recommendations of the Committee

In 2024, it is notable that 100% of FDA decisions following approval AdComms were in concordance with the Committee voting outcome. This means that sponsors preparing for an AdComm should take their preparations very seriously, as the Committee’s expert feedback and voting results are highly likely to influence FDA’s decisions.

While FDA decisions usually align with the recommendation of the AdComm, this is not guaranteed. Typically, we expect to see 1 or 2 FDA approval decisions per year which are discordant with the AdComm vote. Previous research found that 88% of FDA regulatory actions aligned with the AdComm voting results between 2010 and 2021.1 Thus, the 100% concordance rate in 2024 stands out from what we would expect historically.

There is just 1 pending FDA decision from AdComms in 2024 which could potentially break the 100% concordance rate.? The Cardio-renal Drugs Advisory Committee (CRDAC) on October 10th, 2024, endorsed Stealth’s elamipretide for the ultra-rare disease, Barth syndrome, by a split vote of 10 Yes to 6 No. The NDA for elamipretide was assigned a PDUFA date of January 29, 2025.

2. We may see more AdComms in 2025 with no formal voting questions, and other “non-traditional” structures

While not unprecedented, it is rare for AdComms concerning new approvals to forego a formal vote. Approval meetings typically include voting questions that force a clear yes/no on issues crucial to the approval of the application. In the absence of a formal vote, the outcome of the meeting may be difficult to categorize as positive or negative. Both committee members and division directors have pointed out in multiple discussions that the voting clarifies their positions, and our own observations have been that the tenor of the discussion does not always align with the outcome of a vote.

In the absence of a vote, sponsors should focus even more of their efforts on eliciting and encouraging discussion from the Committee which will positively influence FDA’s actions. FDA has consistently indicated that they listen closely to and highly value the Committee discussion (even when there is a vote). Our approach includes defining specific phrases we hope to hear from the Committee at the outset of AdComm preparations to help sponsors succeed in this goal.

In 2024, two AdComms with new approval applications as topics did not include a formal vote. There was no formal voting at the Cellular, Tissue, and Gene Therapies Advisory Committee (CTGT) meeting on November 21st, 2024 to evaluate the confirmatory data to potentially support the conversion of accelerated approval for AstraZeneca’s (AZ’s) anticoagulant reversal agent, Andexxa, to full approval. There was also no formal voting at the AMDAC meeting on September 9, 2024 to evaluate data supporting the NDA for Iterum Therapeutics’ oral sulopenem etzadroxil/probenecid for uncomplicated urinary tract infection (uUTI).

The Oncology Drugs Advisory Committee (ODAC) has historically been a leader in testing out “non-traditional” AdComm innovations. On July 25, 2024, ODAC met to discuss AZ’s sBLA for Imfinzi (durvalumab) for perioperative treatment of resectable NSCLC. However, ODAC was not asked to weigh in specifically on durvalumab; instead voting focused more broadly on criteria for new trial design proposals for perioperative treatment regimens in NSCLC.

3. A new AdComm devoted to rare metabolic diseases indicates that FDA is anticipating new applications and complex regulatory challenges in this disease area

It is rare for a new Advisory Committee to be formed, but when it happens, sponsors should take notice. The formation of the new Genetic Metabolic Drugs Advisory Committee (GeMDAC) was announced in December 2023 to advise the agency on drugs and biologic products for “the diagnosis, prevention or treatment of genetic metabolic diseases.” Genetic metabolic diseases are usually rare or ultra-rare, requiring highly specialized expertise in metabolic genetics and often involving complex regulatory challenges, such as very small treatment populations and limited clinical data.

Sponsors that are developing new therapies for rare genetic metabolic diseases are much more likely to have an AdComm meeting, and the FDA’s establishment of the GeMDAC reinforces this notion. Of note, this is a Center for Drug Evaluation and Research (CDER) committee, focused on drugs and biologics for genetic diseases; the CTGT under the Center for Biologics Evaluation and Research (CBER) will likely continue to review gene therapies. However, given that much drug development in the field of genetic metabolic diseases includes gene therapies, we may see some overlap between these two Committees.

On August 2, 2024, the GeMDAC voted (11 to 5) in support of Zevra Therapeutics’ arimoclomol for the rare lysosomal storage disorder Nieman-Pick disease type C (NPC). FDA followed with an approval of arimoclomol (Miplyffa) on September 30, 2024, to treat neurological symptoms associated with NPC.

4. Conversion of accelerated approval to full approval continues to be a challenge for sponsors, and guidance may have just gotten more stringent in 2025

Historically, accelerated approvals are a hot topic at AdComms. At the heart of an accelerated approval is acceptance that a surrogate endpoint is “reasonably likely to predict clinical benefit.” However, there is often great uncertainty about whether clinical benefit will ever be confirmed. If a drug granted accelerated approval fails to confirm the benefit, FDA is faced with a difficult decision of whether the accelerated approval should be withdrawn, or if the product should be allowed to stay on the market while the sponsor generates confirmatory clinical data.

In 2024, 2 AdComms were held to evaluate the conversion of accelerated approval to full approval – a CTGT meeting to discuss AZ’s Andexxa, and a GIDAC meeting to discuss Ocaliva. In both cases, the Committees determined that there was not enough evidence to support full approval, and FDA subsequently rejected the applications. Both Andexxa and Ocaliva remain available to patients under accelerated approval; however, the potential for withdrawal of accelerated approval remains a possibility.

FDA recently published 2 new guidances regarding accelerated approvals that we may see referenced at future AdComms, and applied in future regulatory decisions. Both guidances could be interpreted as the agency imposing greater restrictions and setting a higher bar for accelerated approval. The December 2024 draft guidance for accelerated approval describes in more detail the considerations for confirmatory trial design, and also details the procedure for expedited withdrawal of accelerated approval. The January 2025 guidance details the agency’s considerations for determining if a confirmatory trial meets the definition of being “underway.”

5. Sponsors preparing for AdComms in 2025 should expect to set foot on the FDA White Oak Campus for live meetings. But, this does not mean “business as usual.”

2025 may mark the first year of fully post-pandemic operations, with in-person meetings back in full swing. However, a changing administration and other organizational changes could impact AdComms in 2025.

In 2024, the slow start to AdComms may have been a hangover effect of the impact of the pandemic on development programs or possibly internal operational considerations at FDA as they started to return to in-person AdComms. The first in-person AdComm post-pandemic was a meeting of the ODAC held on April 12, 2024. Most subsequent meetings were in-person in 2024 held by CDER were in-person, with hybrid meeting components, which will likely continue in 2025. Notably, the 6 AdComms managed by the CBER in 2024 (i.e. CTGTAC, VRBPAC, and BPAC) were all virtual, so, it is possible that virtual AdComms may continue into 2025 for CBER.

We reached out to FDA for further information about future CBER meetings, and they indicated that they will make the determination when they schedule each meeting, so please stay tuned.

Needless to say, a lot is going on behind the scenes at FDA. On October 1, 2024, FDA implemented the most extensive reorganization in FDA history, including the formation of a new unified Human Foods Program, and the reorganization of the former Office of Regulatory Affairs (ORA) into a new office, called the Office of Inspections and Investigations (OII). And we will soon see the departure of several top FDA leaders, including FDA Commissioner, Robert Califf, CDER Director, Patrizia Cavazzoni, and Deputy Commissioner, Namandjé Bumpus.

While there remain many uncertainties as we enter 2025, we know that an AdComm is a crucial opportunity to influence the outcome of an FDA decision. It’s a public event that requires extensive preparation to best represent the product, the company, and the team. It’s crucial to have the right team and the right partner to help you attain your goals.

About the Authors

Angela W. Corona, PhD, is a Senior Scientific Director with BOLDAPPROVALS where she supports teams approaching new drug or biologics approvals. With 10 years of broad medical and regulatory communications experience across a range of therapeutic areas, including neurology/neurodegenerative disease, oncology, and immunology, she has played a key role in preparing teams for AdComms, strategic submission messaging, and other complex regulatory communication challenges. Her PhD training was in neuroscience at The Ohio State University, and she performed post-doctoral research in Alzheimer’s disease at Case Western Reserve University.

Steven C. Cohen is the Managing Director of BOLDAPPROVALS, the division of BOLDSCIENCE that prepares clients for AdComms, regulatory submissions for the approval of new therapeutics (NDAs/BLAs), FDA meetings, and label development. Steven has 33 years of leadership in communication consulting, strategy, and delivery coaching, including 117 AdComm preparations. He has supported numerous health authority interactions at key milestones and led submission messaging workshops. He has trained and coached over 1000 scientists, clinicians, and other leaders across disciplines. Steven earned a bachelor’s degree in French Literature from Wesleyan University. He studied medical science at NY Medical College and marketing, communication, and the Internet at Columbia University.

About BOLDAPPROVALS

BOLDAPPROVALS blends science, communication, and technology to support product approvals. We deliver comprehensive support for FDA Advisory Committee meetings (AdComms), submission messaging, labeling strategy, and health authority interactions.

Our proven methodology integrates in-house scientific expertise with communication consulting to develop compelling, data-driven arguments for persuasive presentations, responses to questions, and briefing materials.

Our highly experienced team has supported over 250 AdComm preparations and aligned teams on messages for regulatory submissions and interactions with health authorities. Our team can address the unique needs of your people, products, and circumstances.

To learn more about how BOLDAPPROVALS can help your team identify and overcome issues, please visit boldapprovals.com, email [email protected], or call Steven Cohen at +1 (646) 930-0453.