FDA September 2025 Highlights: Accelerated Approvals, Transparency Reforms, and New Pathways for Rare and Chronic Conditions
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9/29/20255 min read
FDA September 2025 Highlights: Accelerated Approvals, Transparency Reforms, and New Pathways for Rare and Chronic Conditions
September 2025 marked one of the most dynamic months of the year for the U.S. Food and Drug Administration (FDA), with multiple major actions spanning rare diseases, chronic pain management, post-market transparency, cosmetic safety, and drug repurposing.
From landmark approvals to regulatory modernization, the agency reinforced its commitment to innovation, evidence-based decision-making, and public accountability.
Below is a summary of the month’s most significant developments shaping the current regulatory landscape.
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1. FDA Introduces Rare Disease Evidence Principles (RDEP)
The FDA unveiled its new Rare Disease Evidence Principles (RDEP) to bring clarity and flexibility to the approval process for therapies targeting ultra-rare, genetically defined conditions.
Developed by CDER and CBER, the framework allows drug sponsors to demonstrate substantial evidence of effectiveness through a single adequate and well-controlled study supported by robust confirmatory data — including biomarkers, mechanistic rationale, or case series.
This initiative addresses one of the toughest challenges in regulatory science: limited patient populations that make traditional trial designs unfeasible.
By embracing confirmatory evidence, the FDA aims to accelerate safe access to rare disease therapies while maintaining scientific rigor.
“These principles ensure that FDA and sponsors are aligned on a flexible, common-sense approach within our existing authorities,” said Commissioner Dr. Marty Makary.
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2. FDA Issues Draft Guidance to Advance Non-Opioid Therapies for Chronic Pain
Continuing its broader strategy to address the opioid crisis, the FDA released draft guidance titled “Development of Non-Opioid Analgesics for Chronic Pain”.
The guidance provides clear regulatory expectations for sponsors developing safer pain treatments, with a focus on innovative trial design, patient-reported outcomes, and metrics that demonstrate reductions in opioid use.
This fulfills a requirement under the SUPPORT Act, establishing a roadmap to diversify the chronic pain treatment landscape and reduce reliance on prescription opioids.
“Physicians need more alternatives to opioid medications for patients suffering from chronic pain,” said Dr. Makary. “This guidance helps innovators bring lower-risk therapies to patients faster.”
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3. FDA Enhances Transparency with Real-Time Publication of Complete Response Letters
In a landmark step toward regulatory transparency, the FDA announced that Complete Response Letters (CRLs) — which detail reasons for non-approval — will now be published in real time following issuance to sponsors.
The agency also released 89 previously unpublished CRLs issued since 2024, making previously confidential regulatory decisions accessible to the public through openFDA.
This initiative aims to help drug developers avoid repeated mistakes, inform investors responsibly, and restore trust in the regulatory process.
“By embracing radical transparency, we’re giving invaluable insights to help speed therapies to market and restore public trust,” said Dr. Makary.
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4. FDA Removes REMS Requirement for Caprelsa (Vandetanib)
After over a decade of successful risk management, the FDA officially removed the Risk Evaluation and Mitigation Strategies (REMS) for Caprelsa (vandetanib), a thyroid cancer therapy.
Post-market data demonstrated no cases of Torsades de Pointes or unexplained sudden deaths, confirming that healthcare providers now manage cardiac risks effectively as part of standard clinical practice.
This decision reflects the FDA’s evolving approach to dynamic REMS reassessment, ensuring regulatory controls remain evidence-driven rather than permanent administrative barriers.
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5. FDA Cracks Down on Deceptive Drug Advertising
In partnership with the Department of Health and Human Services (HHS), the FDA launched a sweeping enforcement initiative to combat misleading pharmaceutical advertising — including 100 cease-and-desist letters and thousands of warnings to companies with deceptive marketing content.
The agency also announced plans to close the 1997 “adequate provision” loophole, which allowed companies to omit safety details in broadcast and digital ads.
This move, paired with AI-driven surveillance of digital and influencer content, signals the FDA’s intent to restore integrity in health communication and protect patients from misinformation.
“Drug companies spend up to 25% of their budgets on advertising. Those billions would be better spent on lowering drug prices for Americans,” said Dr. Makary.
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6. FDA Launches FAERS Public Dashboard for Cosmetic Products
Expanding its modernization agenda, the FDA introduced a real-time FAERS Public Dashboard exclusively for cosmetic products.
The platform enables users to search and download adverse event data reported under the Modernization of Cosmetics Regulation Act (MoCRA) — covering categories like moisturizers, hair dyes, and tattoo inks.
The dashboard represents a milestone in post-market surveillance transparency, allowing professionals and consumers to identify potential safety signals early while reinforcing MoCRA’s new compliance expectations for cosmetic manufacturers.
“This real-time dashboard allows the public to help identify potential data signals,” said Dr. Makary.
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7. FDA Grants Accelerated Approval to Forzinity for Barth Syndrome
In a major advance for rare mitochondrial diseases, the FDA granted accelerated approval to Forzinity (elamipretide) — the first therapy for Barth syndrome, a life-threatening disorder primarily affecting males.
Approval was based on improvements in knee extensor muscle strength, a surrogate endpoint reasonably likely to predict patient benefit.
Forzinity received priority review, rare pediatric disease designation, and a priority review voucher, underscoring the agency’s dedication to bringing life-changing treatments to rare disease patients faster.
The approval also highlights how surrogate endpoints and post-market commitments can work together to balance speed and scientific rigor in regulatory decision-making.
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8. FDA Expands Access to Leucovorin for Cerebral Folate Deficiency and Autism Symptoms
In a significant move toward drug repurposing, the FDA initiated approval of leucovorin calcium tablets for cerebral folate deficiency (CFD) — a condition that impairs folate transport into the brain and is linked to autism-related symptoms.
The agency’s review of over a decade of literature and mechanistic data found that leucovorin can improve neurological outcomes in CFD patients, many of whom exhibit developmental delays and communication challenges.
The FDA is now collaborating with GSK, the manufacturer of Wellcovorin, to expand labeling for both adult and pediatric CFD patients.
This step illustrates how repurposing existing drugs can address unmet needs efficiently while maintaining safety oversight.
“We are using gold-standard science and common sense to deliver for the American people,” said Dr. Makary.
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9. FDA Approves New Treatment for Barth Syndrome and Strengthens Rare Disease Pipeline
The FDA’s September actions reaffirmed its focus on rare disease innovation, with several updates — including new guidance frameworks, post-market commitments, and adaptive evidentiary standards.
Together, they form part of a cohesive strategy to advance regulatory flexibility while maintaining patient safety as the agency’s top priority.
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Summary: A Transformative Month for Regulatory Science
September 2025 showcased how the FDA is evolving into a more transparent, flexible, and data-driven regulatory body.
From publishing internal decision documents to leveraging real-world evidence, the agency is building a regulatory ecosystem that integrates innovation, ethics, and efficiency across all stages of product development.
For Regulatory Affairs and Pharmacovigilance professionals, these developments highlight the growing need to:
• Stay informed about emerging FDA frameworks such as RDEP and non-opioid guidance;
• Strengthen data-driven submissions and post-market compliance systems;
• Prepare for a new era of radical transparency and digital safety monitoring;
• Integrate multi-disciplinary collaboration into every stage of regulatory planning.