The Year in Review: 5 Small-Molecule Drugs Approved by the FDA in 2025

Last January, we highlighted five of the powerful new small-molecule drugs approved by the U.S. Food and Drug Administration (FDA) in 2024. This year, we’re back to put the spotlight on five more small molecules that entered the clinical toolbox in 2025. Each of these drugs – as well as the 41 others approved by the FDA in the past year – represents the product of years of discovery and development research, with hundreds of scientists, clinicians, administrators, trial participants, and more playing critical roles to advance these therapeutics into clinical use. As we explore how these five drugs made their way from bench to bedside, we hope to emphasize all of the hard work, dedication, and scientific ingenuity that made it possible. Read on to learn more about a few of the transformative therapeutics that made it to market in 2025!

Journavx (suzetrigine) | Vertex Pharmaceuticals

At the end of January 2025, Vertex Pharmaceuticals announced the FDA approval of Journavx (suzetrigine), a first-in-class non-opioid analgesic for the treatment of adults with moderate to severe acute pain. Suzetrigine is a small molecule that works to inhibit the voltage-gated sodium channel Na_V1.8 by binding to one of its voltage-sensing domains. As a result, nociceptive (i.e., pain-sensing) neurons in the peripheral nervous system are prevented from transmitting pain signals to the central nervous system (CNS). Suzetrigine, also referred to in the literature as VX-548, has been shown to be >31,000-fold more selective for Na_V1.8 than other Na_V channels, and oral administration of suzetrigine was found to be safe and tolerable. In Phase 2 and Phase 3 studies, suzetrigine was found to significantly reduce pain following abdominoplasty and bunionectomy, with results comparable to those of hydrocodone. Additional Phase 4 trials continue to evaluate the efficacy of suzetrigine for pain management following laparoscopic, arthroscopic, and reconstructive surgeries. In light of public health concerns associated with the prescription and use of opioid pain medications, suzetrigine offers a compelling alternative for the treatment of pain without addiction risk or CNS side effects.

Ibtrozi (taletrectinib) | Nuvation Bio

In June 2025, the ROS1 tyrosine kinase inhibitor Ibtrozi (taletrectinib) was approved by the FDA for the treatment of locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC) in adult patients. Tyrosine kinase inhibitors (TKIs) have long been recognized for their potential in the treatment of diverse cancers, with over 50 TKIs already approved by the FDA.  Taletrectinib selectively targets the ROS1 tyrosine kinase, a known oncogenic driver implicated in roughly 2% of NSCLC cases and associated with an increased rate of brain metastasis. First-in-human results for taletrectinib were reported in 2020, demonstrating its safety and tolerability at relevant dosages. The TRUST-I study demonstrated high response rates for taletrectinib in the treatment of ROS1-positive NSCLC, including prolonged progression-free survival in both TKI-naïve and crizotinib-treated patients. The subsequent global TRUST-II study reported similarly positive results and corroborated the clinical efficacy of taletrectinib in the treatment of brain metastases. In addition to its role as a first- and second-line treatment for ROS1-positive NSCLC, taletrectinib is being evaluated as a potential treatment for other cancer types, with a recent study reporting promising preclinical results for the treatment of colorectal carcinoma (CRC).

Ekterly (sebetralstat) | KalVista Pharmaceuticals

In July 2025, KalVista Pharmaceuticals received FDA approval for Ekterly (sebetralstat), a small-molecule plasma kallikrein inhibitor used to treat acute attacks of hereditary angioedema. Hereditary angioedema is a rare genetic disorder causing episodes of swelling that commonly involve the skin, upper airway, and gastrointestinal tract and which can be life-threatening.  The disorder arises from alterations in the gene SERPING1, which lead to disruption of the plasma kallikrein-kinin system and, in turn, excess levels of the inflammatory peptide bradykinin. Based on this mechanistic understanding, scientists at KalVista developed a panel of small-molecule plasma kallikrein inhibitors with desirable pharmacological properties, out of which sebetralstat emerged as a promising therapeutic candidate. A two-part Phase 2 trial investigated the efficacy of oral sebetralstat treatment, reporting that treatment was well tolerated, reduced plasma kallikrein activity, and increased the time before use of conventional attack treatment. A subsequent Phase 3 trial (KONFIDENT) further demonstrated that sebetralstat treatment lessened the severity of angioedema attacks and reduced the time to attack resolution. The approval of sebetralstat as the first oral on-demand treatment for hereditary angioedema offers a significant advantage over previous injectable treatments, for which administration-associated challenges and anxieties have been correlated with poor patient compliance.

Jascayd (nerandomilast) | Boehringer Ingelheim

Jascayd (nerandomilast) was approved by the FDA in October 2025 for the treatment of adults with idiopathic pulmonary fibrosis (IPF). In December, the drug received additional approval for the treatment of progressive pulmonary fibrosis (PPF). Jascayd is a small-molecule preferential inhibitor of phosphodiesterase 4B (PDE4B), an enzyme that hydrolyzes cyclic AMP (cAMP) and plays important roles in cellular signal transduction. In the context of IPF/PPF, inhibition of PDE4B has been shown to inhibit pathways associated with fibrosis and inflammation. A Phase 2 trial of nerandomilast(also known as BI 1015550) demonstrated the drug’s ability to reduce loss of lung function in IPF patients, and a subsequent Phase 3 trial corroborated these findings; IPF patients treated with nerandomilast experienced less reduction in lung function, measured by forced vital capacity (FVC), compared to placebo-treated patients. An analogous Phase 3 trial of PPF patients reported similar findings, with nerandomilast-treated subjects exhibiting a lesser reduction in FVC over 52 weeks compared to placebo-treated subjects. An ongoing follow-up study (FIBRONEER™-ON) seeks to assess the safety and efficacy of long-term nerandomilast treatment in both IPF and PPF patients.

Nereus (tradipitant) | Vanda Pharmaceuticals

The final FDA approval of 2025, coming through on December 30, was given to Vanda Pharmaceuticals’ Nereus (tradipitant), a neurokinin-1 (NK-1) receptor antagonist for the treatment of motion-induced vomiting that represents the first novel therapeutic for motion sickness in over four decades. The NK-1 receptor endogenously binds a peptide known as Substance P, which plays critical roles in neurotransmission and a variety of other biological processes. The presence of Substance P in brain regions associated with emesis led researchers to hypothesize that NK-1 inhibition could represent a promising avenue for the treatment of nausea and vomiting. In 2020, researchers reported the results of the Motion Sifnos study, which demonstrated that tradipitant treatment reduced motion sickness in participants during a four-hour boat trip. Five years later, the same team confirmed these findings in the Motion Syros study, corroborating the efficacy of tradipitant in reducing nausea and vomiting under variable sea conditions. Additional studies have investigated the utility of tradipitant for the treatment of diabetic and idiopathic gastroparesis, atopic dermatitis, and opioid use disorder, highlighting the diverse range of biological roles played by Substance P and the NK-1 receptor.

Are you seeking to identify or develop a small-molecule drug candidate? Momentum Biotechnologies offers an extensive portfolio of services to support drug discovery and development research from target identification through IND-enabling preclinical studies. Connect with our team to explore how these technologies can accelerate your research program!

 

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