In 2025, the U.S. FDA's Center for Drug Evaluation and Research (CDER) approved a total of 46 new drugs. Although this represents a continued decline compared with 2023 and 2024, the overall portfolio was notably diverse and highly innovative. More than half of the approved products were first-in-class therapies, highlighting a clear industry shift toward a quality-over-quantity development strategy.

Figure 1. FDA Approved Drugs, source: reference [1]

Therapeutic Landscape: Oncology Leads

By therapeutic area, oncology remained the dominant focus. Of all CDER approvals, 16 drugs (35%) were indicated for cancer, exceeding the average proportion seen over the past five years. However, a noteworthy trend emerged: only two of these oncology drugs are projected to achieve annual sales exceeding USD 2 billion. This suggests that even breakthrough therapies are facing increasing market fragmentation and value dilution, and that concentrating solely on high-profile therapeutic areas is no longer sufficient to ensure commercial success.

At the same time, meaningful progress was made across several other therapeutic areas:

• ◆ Cardiovascular (5 drugs, 11%): Advances were led by next-generation PCSK9 inhibitors.
• ◆ Allergy and Inflammatory Diseases (4 drugs, 9%): Therapies such as BTK inhibitors continue to expand into broader immune-mediated indications.
• ◆ Infectious Diseases (4 drugs, 9%): A major milestone was achieved with the approval of the first oral antibiotic with a novel mechanism of action in nearly 60 years.
• ◆ Rare Diseases (6 drugs, 13%): Approvals continued to grow, driven in part by innovation in gene therapies and other advanced technologies.

Technological Breakthroughs: Three Innovation Paths

Small-Molecule Drugs: Allosteric and Covalent Inhibitors Gain Momentum

Small-molecule drugs continued to dominate approvals by volume, but the 2025 data tell a different story on innovation. More than 70% of approved small molecules featured novel mechanisms of action, clearly overturning the long-held view that small molecules lack meaningful innovation.

Allosteric inhibitors: By binding to allosteric sites rather than active sites, these drugs achieve high target selectivity. For example, GOMEKLI (mirdametinib), an allosteric MEK1/2 inhibitor for neurofibromatosis type 1 (NF1), shows approximately 100-fold greater selectivity for mutant targets compared with traditional MEK inhibitors. MYQORZO™ (aficamten) , a cardiac myosin inhibitor for the treatment of adults with symptomatic obstructive hypertrophic cardiomyopathy (oHCM), inhibits force in cardiac muscle by altering myosin's biochemical activity without changing thick filament structure.

Covalent inhibitors: Drugs such as the EGFR inhibitor Zegfrovy (sunvozertinib), the HER2 inhibitor Hernexeos (zongertinib), and the BTK inhibitor Wayrilz (rilzabrutinib) form covalent bonds with their targets to achieve sustained inhibition. This approach can reduce dosing requirements and help overcome certain resistance mutations.

Breakthroughs in new targets: Eight approved drugs act on entirely new protein targets. Examples include Tryptyr (acoltremon), a first-in-class TRPM8 thermoreceptor agonist indicated for the treatment of the signs and symptoms of dry eye disease, and BRINSUPRI™ (brensocatib), a first-in-class oral DPP1 inhibitor for non-cystic fibrosis bronchiectasis (NCFB), offering new treatment options for diseases that previously lacked effective therapies.

Oligonucleotide Therapies: siRNA and ASO Enter a Phase of Clinical Maturity

In 2025, three oligonucleotide drugs were approved, all of them first-in-class therapies. Their approvals signal that siRNA and ASO technologies have moved beyond early proof of concept and into broader clinical adoption.

• ◆ Qfitlia (fitusiran): Qfitlia is a small interfering RNA (siRNA) therapy, the first antithrombin-lowering therapy approved for use in hemophilia. It is administered by subcutaneous injection, starting at once every 2 months, which is less frequent than other existing options.
• ◆ DAWNZERA™ (donidalorsen): Donidalorsen is an RNA-targeted antisense oligonucleotide that specifically and reversibly reduces plasma prekallikrein (PKK) production in the liver. Donidalorsen is labeled for self-administration of an 80-mg dose via subcutaneous autoinjector once every 4 or 8 weeks -- less frequent dosing compared with other options for prophylaxis.
• ◆ Redemplo (plozasiran): Plozasiran, an RNA interference therapeutic, reduces apoC-III production, impacting triglyceride metabolism in familial chylomicronemia syndrome (FCS) patients. Redemplo significantly lowers very high triglycerides, showing an 80% median reduction in fasting triglycerides in the Phase 3 PALISADE study after 10 months with the 25mg dose, compared to only 17% for placebo.

Antibody–Drug Conjugates (ADCs): Target Expansion and Payload Innovation in Parallel

In 2025, two new ADCs— DATROWAY® (datopotamab deruxtecan-dlnk) and Emrelis (telisotuzumab vedotin) —received regulatory approval.

Although both EMRELIS and DATROWAY are ADCs, they differ substantially in key structural design elements, including linker length, hydrophobicity control, payload chemistry, and drug-to-antibody ratio (DAR) distribution. EMRELIS is designed with a stronger focus on systemic stability and a tightly managed safety margin, whereas DATROWAY pursues a more aggressive approach aimed at maximizing intratumoral payload release and cytotoxic potency. These design-level differences highlight a broader evolution in ADC development—from demonstrating efficacy to carefully balancing efficacy, tolerability, and indication-specific fit.

In-Depth Review of Potential Blockbusters 

Keytruda Qlex (pembrolizumab + berahyaluronidase alfa-pmph)

Projected peak annual sales: USD 9.3 billion

Keytruda Qlex is a subcutaneous injection formulation of pembrolizumab, a programmed death receptor-1 (PD-1)-blocking antibody, and berahyaluronidase alfa, an endoglycosidase which enhances dispersion and permeability to enable subcutaneous administration of pembrolizumab.

Compared with the original IV formulation, Keytruda Qlex can be administered in just 1–2 minutes, versus approximately 30 minutes for IV infusion. This significantly reduces treatment time and may improve patient convenience and clinic efficiency. Analysts at Evaluate project peak annual sales of approximately USD 9.3 billion for the subcutaneous formulation.

Datroway (Datopotamab Deruxtecan)

Projected peak annual sales: USD 5 billion

Datopotamab deruxtecan, jointly developed by Daiichi Sankyo and AstraZeneca, is a specifically engineered TROP2-directed DXd ADC used for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer and EGFR-mutated non-small cell lung cancer (NSCLC).

AstraZeneca projects peak annual sales exceeding USD 5 billion. However, the drug faces strong competition from trastuzumab deruxtecan (T-DXd). To achieve meaningful differentiation, Datopotamab deruxtecan will likely need to demonstrate advantages such as improved central nervous system penetration or a more favorable safety profile.

Yeztugo (lenacapavir) 

Projected peak annual sales: USD 4.5 billion

Yeztugo is an injectable HIV-1 capsid inhibitor, which can be used as pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV in adults and adolescents weighing at least 35kg. It is the first and only 6-month option available in the United States for people who need or want PrEP. Data show that ≥99.9% of participants who received Yeztugo in the Phase 3 PURPOSE 1 and PURPOSE 2 trials remained HIV negative.

Lenacapavir has a distinct, multi-stage mechanism of action that sets it apart from currently approved antiviral therapies. Unlike most antivirals, which target a single step in viral replication, lenacapavir interferes with multiple stages of the HIV lifecycle and has shown no known in vitro cross-resistance to existing antiviral drug classes.

Gilead has announced access strategies for high-incidence regions. If effectively implemented, Yeztugo could represent one of the most important turning points in the history of HIV prevention, significantly improving PrEP coverage and adherence. Analysts estimate peak annual sales of approximately USD 4.5 billion.

Brinsupri (Brensocatib)

Projected peak annual sales: USD 4.3 billion

Brensocatib is the world’s first dipeptidyl peptidase-1 (DPP1) inhibitor and the first drug specifically approved for non–cystic fibrosis bronchiectasis, a chronic inflammatory lung disease. By targeting neutrophil serine proteases, it introduces a novel disease-modifying mechanism to a field that has seen little innovation over the past decade.

The drug received FDA approval in August and European Commission approval in November. However, its development has not been without setbacks. A 2024 clinical trial in chronic rhinosinusitis failed, highlighting the risks associated with indication expansion.

Despite this, TD Cowen analysts continue to model peak annual sales of approximately USD 4.3 billion. Insmed expects topline results from a Phase 2b study (CEDAR) in hidradenitis suppurativa in the second quarter of 2026, which could further define the drug’s long-term potential.

JOURNAVX (suzetrigine)

Projected peak annual sales: USD 2.6 billion

Journavx (suzetrigine) is a non-opioid therapy approved for the treatment of moderate to severe acute pain in adults. Acute pain is commonly caused by surgery, injury, or trauma and is often treated with opioids, which carry a significant risk of long-term dependence and opioid use disorder.

Suzetrigine selectively inhibits the NaV1.8 voltage-gated sodium channel, which is expressed in peripheral sensory neurons responsible for transmitting pain signals. Importantly, NaV1.8 is not expressed in the central nervous system. As a result, Journavx blocks pain signal transmission to the spinal cord and brain without affecting brain reward pathways, eliminating the biological basis for addiction.

Clinical data are encouraging. Across two trials involving more than 2,000 patients, Journavx demonstrated meaningful pain relief with no signals of abuse or dependence. According to Visible Alpha, sales are projected to reach USD 105.8 million in 2025 and USD 362 million in 2026, with peak global sales estimated at USD 2.6 billion by 2032.

Conclusion

The FDA’s 2025 new drug approvals serve as a clear reflection of where the industry is heading. Counting approvals alone is no longer a meaningful measure of progress; the focus has shifted decisively toward quality and real clinical value. From precision “biological missiles” in oncology such as ADCs, to Yeztugo—named a Breakthrough of the Year for redefining HIV prevention—and Journavx, which offers new hope in addressing opioid dependence, each innovation represents both a scientific advance and a commitment to improving human health. Together, these therapies highlight not only technological progress, but also a deeper understanding of patient needs and a stronger sense of responsibility across the pharmaceutical industry.

References:
[1] Mullard, A. (2026). 2025 FDA approvals. https://doi.org/10.1038/d41573-026-00001-z