Latest FDA Regulatory Updates: Leadership, Rare Disease Evidence & New Initiatives

Kelsey Lenoch, Associate Director, Regulatory Affairs at Boyds, explores the latest developments and regulatory updates at the FDA and offers guidance for sponsors, clinicians, and scientists navigating this complex environment.

Leadership changes at the FDA

Following the departure of several senior FDA officials in 2025, incoming leadership at the FDA is poised to influence the future of the drug development industry. Dr. Vinay Prasad has returned as Director of the Center for Biologics Evaluation and Research (CBER) after a brief departure. Meanwhile, Dr. George Tidmarsh was appointed in July 2025 as Director of the Center for Drug Evaluation and Research (CDER), bringing with him a blend of academic, clinical, and biotech experience. Dr. Mike Davis has also joined as CDER Deputy Director, with a background in psychedelic drug research. These appointments reflected a leadership team with diverse expertise across academia, clinical practice, and industry, which may shape how the Agency approaches innovation and emerging therapeutic areas.

However, in early November 2025, Dr. Tidmarsh resigned from his role as CDER Director after being placed on administrative leave in light of “serious concerns about his personal conduct” and pending investigation by the Department of Health and Human Services (HHS). The departure adds to the recent wave of high-level turnover at FDA. He has since been replaced by Dr. Richard Pazdur, a longtime FDA employee who is the director of the Agency’s Oncology Center for Excellence, a position he will continue to hold until a successor is appointed. This marks a departure from FDA Commissioner Dr. Marty Makary’s prior string of external hires to positions of prominence.

As leadership changes often precede shifts in regulatory priorities, it is important for stakeholders to stay informed about new guidance documents and public statements from CBER and CDER. Early engagement with the Agency remains advisable, as it can help clarify expectations and foster relationships with reviewers during this period of transition.

Staffing challenges and review delays

While CBER and CDER are currently meeting review timelines, the Office of Orphan Products Development is experiencing significant delays, with review periods stretching up to four or five months compared to the anticipated 90 days. The office has been transparent about being short-staffed, which means that sponsors working on orphan or rare disease products should plan for potential delays and consider building extra time into their regulatory strategies.

Rare disease evidence principles

The FDA’s Rare Disease Innovation Hub, a collaboration between CBER and CDER, has released new Rare Disease Evidence Principles, emphasizing early and frequent engagement with regulators, specifically for ultra-rare diseases affecting 1,000 patients or fewer. The Agency appears poised to offer a formal pathway for early dialogue to align on trial design, endpoints, and clinical feasibility, recognizing the unique challenges of ultra-rare diseases, such as small patient populations that may require creative trial designs, as well as alternative endpoints. Sponsors will be encouraged to leverage the new principles to justify innovative approaches, such as single-arm trials or the use of historical controls.

Evolving clinical trial endpoints

In a recent joint meeting, the FDA and the American Association for Cancer Research (AACR) discussed exploring alternative, clinically meaningful endpoints for oncology clinical trials. Citing one example, they noted GSK’s drug approval for Ojjaara (myelofibrosis) used the Myelofibrosis Symptom Assessment Form Total Symptom Score, a patient-reported outcome, as the primary endpoint, with splenic response rate as a secondary endpoint. While overall survival remains as the “gold standard” oncology endpoint, sponsors may be encouraged (where relevant) to develop disease-specific endpoints in collaboration with patients, investigators, and regulators, and to consider composite or surrogate endpoints that reflect meaningful clinical benefit and are feasible in small populations. Standardization may be a key future step to ensure, where possible, that novel endpoints can be consistently measured across sites and studies.

Circulating tumour DNA (ctDNA) was another topic discussed, and continues to emerge as a promising biomarker of disease severity in cancers such as colorectal, lung, and lymphoma. However, the FDA cautioned they are not currently considering ctDNA as a primary efficacy endpoint, while noting they support its use primarily for risk stratification or post-hoc analyses. Sponsors were further advised of the potential need for standardization of ctDNA assays to ensure they are validated and reproducible across laboratories, which may require more frequent and prospectively designed sample collection from study participants. For now, ctDNA may be better used to enrich patient populations or as a secondary endpoint, rather than as a primary measure of efficacy.

Transparency in regulatory decisions

The FDA is moving toward greater transparency by releasing Complete Response Letters (CRLs) for non-approved drug and biologics applications. Although CRLs from applications that were eventually approved have previously been made available, this new initiative to publish CRLs from non-approved applications aims to increase transparency and help the industry learn from prior regulatory challenges. While this approach offers the benefit of shared insight and enhances public understanding of the regulatory process, it also presents potential risks, such as competitive disadvantages for sponsors of innovative medicines and the possibility of misinterpretation or reputational harm. Sponsors should prepare for the possibility of public disclosure by ensuring that their submissions and responses to FDA requests for information are robust and well-documented. For example, Capricor Therapeutics has made its response letter to the FDA regarding a CRL for a recent biologics application publicly available to provide context and transparency about its interactions with the Agency, leading up to the application’s submission. Engaging legal and communications teams to develop a plan for responding to public release of regulatory correspondence is also advisable.

New FDA initiatives: Commissioner’s National Priority Vouchers and the FDA Precheck Program

Since the announcement of the pilot program in June 2025, the FDA has unveiled the first recipients of the Commissioner’s National Priority Vouchers. The nine selected sponsors will benefit from enhanced communication with review staff, a streamlined review process, and a decision from FDA on their NDA or BLA within one to two months of filing a complete application. To be eligible, a drug or biologic must address at least one major national priority such as an unmet medical need, a public-health crisis, domestic manufacturing, or affordability. Application instructions, further details on eligibility criteria, and answers to frequently asked questions are available on the Commissioner’s National Priority Voucher Program website.

In addition, the proposed FDA Precheck Program aims to accelerate and promote an increase in domestic pharmaceutical manufacturing by improving regulatory predictability and facility readiness, and by expediting review timelines. While details are still emerging, a public meeting has been held to discuss the program and solicit industry feedback. Sponsors should monitor FDA announcements for further specifics and assess their eligibility, considering early application if they are US-based manufacturers.

Support with navigating the US regulatory landscape

In this dynamic regulatory environment, it is essential to stay informed and agile, as regulatory priorities can shift quickly with new leadership and policy changes.

Our regulatory professionals have long-standing relationships with the FDA and can provide clients with specialist knowledge and guidance to help support their regulatory submissions. Speak to the team today.