Introduction: Navigating a Year of Transition
In 2025, the U.S. Food and Drug Administration (FDA) Center for Drug Evaluation and Research (CDER) approved 46 novel therapeutic agents. While this figure represents a slight decline from the five-year rolling average of 48, it remains significantly higher than the long-term historical average of 36 approvals per year recorded since 1993. This volume reflects a pharmaceutical industry that continues to push the boundaries of molecular biology, even as it faces a volatile regulatory and political climate. For clinicians and researchers, 2025 marks a pivotal year characterized by the diversification of established drug classes, the arrival of long-awaited first-in-class mechanisms for chronic conditions, and a shift toward patient-centric delivery methods.
Highlights of the 2025 Approval Cycle
The therapeutic landscape of 2025 was dominated by several key trends:
1. Oncology remains the primary driver of innovation, accounting for 35% of all new approvals.
2. The approval of the 100th kinase inhibitor, remibrutinib, signaling the expansion of this class into non-oncological indications.
3. Major breakthroughs in non-opioid pain management and chronic respiratory diseases through first-in-class mechanisms.
4. Significant regulatory restructuring and the introduction of controversial review pathways, such as the Commissioner’s National Priority Voucher (CNPV).
Oncology: From Infusion to Innovation
Oncology continues to be the most active area of drug development. Of the 46 approvals, 16 were dedicated to cancer treatment. However, the focus has shifted from discovering entirely new targets to refining existing blockbusters and advancing antibody-drug conjugates (ADCs).
The Evolution of Pembrolizumab
A standout approval in 2025 was Merck’s subcutaneous formulation of pembrolizumab (Keytruda) in combination with berahyaluronidase alfa. Since its initial approval in 2014, pembrolizumab has become a cornerstone of immuno-oncology. The new subcutaneous delivery system utilizes berahyaluronidase alfa—a recombinant human hyaluronidase—to temporarily degrade the extracellular matrix in the subcutaneous tissue, facilitating the absorption of large-volume biologics. This formulation is expected to significantly reduce the treatment burden on patients and healthcare systems by transitioning therapy from long intravenous infusions to rapid injections. Analysts project that this subcutaneous version could reach peak sales of $9.3 billion, securing its place as a top-tier revenue generator.
The Rise of ADCs and PD-L1 Diversity
The ADC field saw the approval of datopotamab deruxtecan (Dato-DXd), a TROP2-directed agent for hormone receptor-positive, HER2-negative breast cancer. This approval further validates the ADC platform’s ability to deliver potent cytotoxic payloads with high precision. Additionally, with the approval of penpulimab (Akeso Biopharma), the total number of approved PD-(L)1 inhibitors has reached 12, indicating a highly competitive but mature market.
Addressing Unmet Needs: Respiratory and Pain Management
Beyond oncology, 2025 delivered two major ‘first-in-class’ approvals that address significant gaps in clinical practice: bronchiectasis and acute pain.
Brensocatib: A New Paradigm for Bronchiectasis
For decades, the treatment of non-cystic fibrosis bronchiectasis was limited to airway clearance and antibiotics. Insmed’s brensocatib, a dipeptidyl peptidase 1 (DPP1) inhibitor, is the first drug approved to target the underlying pathophysiology of the disease. By inhibiting DPP1, the drug prevents the activation of neutrophil serine proteases (NSPs) during neutrophil maturation in the bone marrow. High levels of NSPs in the lungs are associated with the inflammation and tissue damage seen in bronchiectasis. Clinical data suggests that brensocatib can reduce the frequency of pulmonary exacerbations, offering a new hope for the half-million patients in the U.S. suffering from this debilitating condition.
Suzetrigine: The Quest for Non-Opioid Pain Relief
The approval of Vertex’s suzetrigine (VX-548) represents a milestone in the decades-long search for effective non-opioid analgesics. Suzetrigine is a selective inhibitor of the voltage-gated sodium channel NaV1.8. Unlike previous attempts to target NaV1.7, which failed in clinical trials, targeting NaV1.8 has proven effective in blocking pain signals in the peripheral nervous system without the central nervous system side effects associated with opioids. While its sibling molecule, VX-993, failed in Phase II trials later in the year, suzetrigine stands as a proof-of-concept for precision analgesia.
Expanding the Utility of Kinase and PDE4 Inhibitors
The year 2025 also saw established drug classes ‘pivot’ toward new indications. The approval of remibrutinib (Rhapsido) for chronic spontaneous urticaria marks the 100th FDA-approved kinase inhibitor. This Bruton’s tyrosine kinase (BTK) inhibitor highlights the transition of the BTK class from B-cell malignancies to autoimmune and inflammatory conditions. Similarly, rilzabrutinib was approved for immune thrombocytopenia.
In the respiratory space, Boehringer Ingelheim’s nerandomilast became the first phosphodiesterase 4 (PDE4) inhibitor approved for idiopathic pulmonary fibrosis (IPF). While PDE4 inhibitors have long been used in COPD and psoriasis, nerandomilast’s selectivity for the PDE4B isoform allows it to modulate fibrotic pathways in the lung, providing the first new treatment option for IPF in over a decade.
Novel Modalities: Affibodies and Lipid Management
Innovation in 2025 was not limited to small molecules and monoclonal antibodies. LIB Therapeutics received approval for lerodalcibep, a PCSK9 inhibitor based on affibody technology. Affibodies are small, highly stable proteins that act as antibody mimetics. Lerodalcibep offers a small-volume, once-monthly subcutaneous injection that can be stored at room temperature, providing a more convenient alternative to existing PCSK9 monoclonal antibodies. This approval reflects a broader trend of developing ‘next-generation’ biologics that improve upon the pharmacokinetic and storage profiles of first-generation therapies.
The Regulatory Climate: Turmoil and Transparency
While the drug pipeline remained productive, the internal environment at the FDA was tumultuous. Following the appointment of Robert F. Kennedy Jr. to lead the Department of Health and Human Services, the agency saw a turnover of nearly 18% of its staff in the CDER and CBER divisions. The CDER specifically cycled through five directors within a single year.
Despite this instability, the FDA introduced the Commissioner’s National Priority Voucher (CNPV) pilot program. This program aims to shorten the review cycle for critical drugs from 10–12 months to just 2 months. However, the program has faced criticism from internal staff and watchdog groups who fear that such accelerated timelines may politicize the approval process and compromise safety standards.
In a move toward greater transparency, the FDA also began publishing edited versions of Complete Response Letters (CRLs), which detail why a drug’s application was rejected. This provides the scientific community with valuable insights into the pitfalls of drug development, as seen in the rejections of apitegromab (due to manufacturing issues) and vusolimogene oderparepvec (due to trial design heterogeneity).
2026 Outlook: The Era of Targeted Protein Degradation
Looking ahead to 2026, the medical community is closely watching the progress of vepdegestrant, a PROTAC (Proteolysis-Targeting Chimera) being developed by Arvinas and Pfizer for breast cancer. If approved, it would be the first targeted protein degrader on the market. Unlike traditional inhibitors that merely block a protein’s function, PROTACs tag the target protein for destruction by the cell’s own proteasome. This modality has the potential to overcome resistance mechanisms that plague current therapies and could open the door to targeting ‘undruggable’ proteins.
Conclusion
The 2025 FDA approval landscape demonstrates the pharmaceutical industry’s resilience and its ability to deliver meaningful clinical advancements despite regulatory headwinds. From the milestone of the 100th kinase inhibitor to the birth of NaV1.8 as a viable pain target, the therapies approved this year offer clinicians a more nuanced and powerful toolkit. As we move into 2026, the focus will likely remain on enhancing patient convenience through better delivery systems and exploring the vast potential of protein degradation and molecular glues.
References
1. Nature Reviews Drug Discovery. (2026). FDA drug approvals in 2025. Nature Reviews Drug Discovery, 25(1), 5-12.
2. U.S. Food and Drug Administration. (2025). Novel Drug Approvals for 2025. CDER Reports.
3. Insmed Incorporated. (2025). Clinical efficacy of brensocatib in bronchiectasis: Results from the ASPEN Phase 3 trial.
4. Vertex Pharmaceuticals. (2025). Suzetrigine (VX-548) for the treatment of acute pain: A summary of pivotal trials.
