Truseltiq (infigratinib) / Novartis, BridgeBio, Pfizer, LianBio, Xediton Pharma, Juniper Bio, Kyowa Kirin - LARVOL DELTA

Systemic Administration of FGF Receptor Inhibitor BGJ398 Improves Osteoarthritis and Chronic Pain in Sickle Cell Disease Mice (ASBMR 2025) - No abstract available

Late-breaking abstract • Preclinical • Genetic Disorders • Hematological Disorders • Immunology • Osteoarthritis • Pain • Rheumatology • Sickle Cell Disease

Infigratinib Improves Skull Measures In A Mouse Model of Crouzon/Pfeiffer Syndromes (ASBMR 2025) - No abstract available

Late-breaking abstract • Preclinical

Low dose infigratinib is an effective strategy in improving bone growth in an hypochondroplasia mouse model (ASBMR 2025) - No abstract available

Preclinical

Low dose infigratinib is an effective strategy in improving bone growth in an hypochondroplasia mouse model (ASBMR 2025) - No abstract available

Preclinical

Discovery of Potent FGFR2/3 Inhibitors to Overcome Mutation Resistance and Treat Achondroplasia. (PubMed, ACS Med Chem Lett) - "Through structural hybridization of Tyra-300 and LY2874455, we developed compound 23, a new dual-target FGFR2/3 inhibitor demonstrating potent activity against both wild-type and mutant FGFR3. In preclinical ACH mouse models, compound 23 showed a dose-dependent improvement in growth rate, with significantly enhanced efficacy versus infigratinib at equivalent doses. This work presents a new structural scaffold for developing FGFR3 kinase inhibitors to target pathogenic FGFR3 mutations and treat ACH."

Journal • Endocrine Disorders • Genetic Disorders • FGFR2 • FGFR3

Sleep-disordered breathing in children with achondroplasia assessed by polysomnography: a retrospective chart review. (PubMed, Arch Dis Child) - "Sleep-disordered breathing was present in 85% of 80 children with achondroplasia, with 21% being asymptomatic. Respiratory parameters did not correlate with foramen magnum stenosis severity and improved after 1 year of treatment in those treated with a precision therapy."

Journal • Retrospective data • CNS Disorders • Genetic Disorders • Pediatrics • Respiratory Diseases • Sleep Apnea • Sleep Disorder

Genetics of short stature. (PubMed, Curr Opin Pediatr) - "Incorporating genetic testing into the routine investigation of short stature improves diagnostic accuracy, enables early discussion of prognostic outcomes, and facilitates precision therapy. Timely identification of specific gene variants helps avoid ineffective treatments - such as growth hormone in resistant genotypes - and supports the adoption of personalized medicine interventions."

Journal • Review • Genetic Disorders • Idiopathic Short Stature • Orthopedics • ACAN • FGFR3 • LZTR1 • MATN3

Infigratinib low dose therapy is an effective strategy to treat hypochondroplasia. (PubMed, J Bone Miner Res) - "We report results of a step-wise evaluation of the therapeutic relevance of infigratinib for hypochondroplasia: in silico assessment of infigratinib with hypochondroplasia associated FGFR3 variants suggest strong interaction; in vitro, infigratinib showed potent inhibitory effect; in a mouse model of hypochondroplasia (Fgfr3N534K/+), infigratinib resulted in significant improvement in skeletal growth. These data in addition to the clinical results from the Phase 2 study conducted in children with achondroplasia provide support for the development of infigratinib in the treatment of hypochondroplasia."

Journal • Genetic Disorders • Orthopedics • FGFR1 • FGFR3

Oral Infigratinib Therapy in Children with Achondroplasia. (PubMed, N Engl J Med) - No abstract available

Journal • Genetic Disorders

Oral Infigratinib Therapy in Children with Achondroplasia. (PubMed, N Engl J Med) - No abstract available

Journal • Genetic Disorders

Oral Infigratinib Therapy in Children with Achondroplasia. Reply. (PubMed, N Engl J Med) - No abstract available

Journal • Genetic Disorders

Fibroblast growth factor receptor alterations and resistance mechanisms in the treatment of pediatric solid tumors. (PubMed, Cancer Drug Resist) - "Effects of the pan-FGFR inhibitor infigratinib (BGJ398) on pediatric cancer cell line viability and migration were evaluated by continuous live cell imaging and compared to FGFR gene expression... Adult and pediatric cancers share common mechanisms of FGFR activation but differ in overall alteration rates and relative abundance of specific aberrations. Preliminary experimental data indicate the therapeutic potential of FGFR inhibitors and suggest mechanisms of resistance in the treatment of pediatric cancers."

Journal • Neuroblastoma • Oncology • Pediatrics • Solid Tumor • FGFR • FGFR1

A dual readout embryonic zebrafish xenograft model of rhabdomyosarcoma to assess clinically relevant multi-receptor tyrosine kinase inhibitors. (PubMed, Front Oncol) - P1/2 | "MRTKIs regorafenib and infigratinib were used at a concentration of 0.1uM added to the fish water 4 hours post cell inoculation. We have developed an embryonic zebrafish xenograft model of RMS, which allows assessment of tumour growth, vascularisation initiation and therapeutic responses to clinically relevant MRTKIs. The identification of VEGF-A secretion as potential biomarker for Regorafenib response and the separation of therapeutic effects on tumour growth and neovascularisation suggests additional value of our model for response prediction to MRTKIs."

Journal • Preclinical • Oncology • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • FGF2 • PDX1

Combined inhibition of EGFR and FGFRs with Cetuximab and Infigratinib showed effectiveness and relevance in proliferation and migration of HNSCC cell lines. (PubMed, Biochim Biophys Acta Mol Basis Dis) - "This study shows that combination of CTX and BGJ was most effective against cell lines, highlighting the crucial roles of EGFR and KGFR, with KGFR potentially mediating effects of BGJ. The findings suggest that adding targeted therapies for receptors on relevant cell subpopulations may enhance outcomes in therapy."

Journal • Preclinical • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EGFR

Genomics-led approach to drug testing in models of undifferentiated pleomorphic sarcoma. (PubMed, Mol Oncol) - "This was further confirmed to be efficacious in an ex vivo tumour slice model. Taken together, our results demonstrate the rationale for utilising genomic data to identify drug classes targeting druggable events in low-prevalence cancers and indicate that trametinib alone or in combination with infigratinib should be further explored for clinical UPS management."

Journal • Oncology • Sarcoma • Solid Tumor • Undifferentiated Pleomorphic Sarcoma • CDK6 • EGFR • FGFR • JUN • PTEN • RB1

Smooth Muscle Fibroblast Growth Factor Signaling Regulates Vascular Smooth Muscle Cell Plasticity and Protects Against Hypoxia-Induced Pulmonary Hypertension (ATS 2025) - "We show that hypoxia-induced proliferation of Human Pulmonary Artery Smooth Muscle Cells (HPASMC) in vitro was prevented in the presence of the FGF inhibitor, BGJ398...Additionally, analysis of single-cell RNA sequencing data from Group 3 PH patients showed increased expression of similar SMC sub-phenotypes. These data suggest the potential for a dual beneficial effect of activation of FGF signaling, both in regulating EC-SMC interactions and directly preventing SMC remodeling."

Bronchopulmonary Dysplasia • Cardiovascular • Chronic Obstructive Pulmonary Disease • Congestive Heart Failure • Heart Failure • Immunology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • FGF • FGF2 • FGFR1

Advancing Ocular Safety Profile Assessment: A Novel Grading Scale for Ocular Adverse Reactions Associated with Bemarituzumab. (PubMed, Ophthalmol Ther) - "Fibroblast growth factor receptors (FGFRs), expressed across various parts of the eye, can become unintended targets of FGFR inhibitors such as erdafitinib, infigratinib, and pemigatinib, leading to ocular adverse events (AEs) affecting the ocular surface and retina. This grading scale is being used across the clinical development program for bemarituzumab to precisely characterize the ocular safety profile, enabling cross-specialty collaboration between oncologists and eye care providers to implement appropriate management strategies. This commentary article highlights the efforts led by Amgen in collaboration with regulatory, medical, and academic fields to develop tools that facilitate early recognition of adverse reactions and appropriate interventions for patient care."

Journal • Oncology • Ophthalmology

Discovery of LC-SF-14, a selective dual inhibitor of SHP2 and FGFR for the treatment of FGFR2-driven gastric cancer. (PubMed, Eur J Med Chem) - "A previous study demonstrated the synergistic effect of the allosteric SHP2 inhibitor SHP099 and the FGFR inhibitor BGJ398, suggesting a potential combined targeted therapeutic option for cancer. LC-SF-14 effectively prevented the phosphorylation of FGFR2 and downstream signaling, resulting in tumor regression in vivo. These results indicate that the bifunctional molecule LC-SF-14, the first PTP- and receptor tyrosine kinase (RTK)-targeted dual inhibitor, is a promising lead for the treatment of cancers bearing SHP2 and FGFR oncogenic drivers."

Journal • Gastric Cancer • Oncology • Solid Tumor • FGFR2

Design of the ACCEL study: A Prospective Clinical Assessment Study in Children with Hypochondroplasia (ESPE-ESE 2025) - P | "Prospective data from this study will contribute to the characterization of the natural history of HCH and serve as a baseline for evaluation of infigratinib as a potential treatment option for children with HCH in future interventional studies."

Clinical • Orthopedics • FGFR1 • FGFR3

Case Report: FGFR2 inhibitor resistance via PIK3CA and CDKN2A/B in an intrahepatic cholangiocarcinoma patient with FGFR2-SH3GLB1 fusion. (PubMed, Front Oncol) - "After failure of FGFRi treatment (Lenvatinib and Infigratinib) ten months later, repeated NGS analysis revealed a new gain-of-function mutation in PIK3CA and a homozygous deletion of CDKN2A/B, potentially representing an acquired resistance mechanism. The emerging acquired resistance to FGFR inhibitor treatment has implications for subsequent treatment strategies."

Journal • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • CDKN2A • CDKN2B • FGFR2 • PIK3CA

Development of an initial triple combination therapy targeting EGFR, AXL, and FGFR for EGFR-mutated non-small cell lung cancer (AACR 2025) - "Our findings demonstrate that the FGF2-FGFR1 signaling pathway contributes to adaptive resistance to the combination of osimertinib and ONO-7475 in EGFR-mutated NSCLC with high AXL expression. The triple combination therapy of osimertinib, ONO-7475, and BGJ398 showed safety and prevented tumor regrowth in CDX models, suggesting that this regimen has the potential to improve outcomes for patients with EGFR-mutated NSCLC."

Combination therapy • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • AXL • EGFR • FGF2 • FGFR • FGFR1 • MYC

Evaluate the Efficacy and Safety of KK8398 in Patients With Achondroplasia（AOBA Study） (clinicaltrials.gov) - P3 | N=6 | Recruiting | Sponsor: Kyowa Kirin Co., Ltd.

New P3 trial • Genetic Disorders

PROPEL3: A Study to Evaluate the Efficacy and Safety of Infigratinib in Children and Adolescents With Achondroplasia (clinicaltrials.gov) - P3 | N=110 | Active, not recruiting | Sponsor: QED Therapeutics, Inc. | Enrolling by invitation ➔ Active, not recruiting

Enrollment closed • Genetic Disorders

Longitudinal Genomic Analysis to Fine-Tune Targeted Therapy: Results of the Phase II LOGIC 2 Trial in Patients With BRAF V600-Mutant Metastatic Melanoma. (PubMed, Clin Cancer Res) - P2 | "LOGIC 2 supports the use of encorafenib plus binimetinib for treatment naive and previously treated locally advanced unresectable or metastatic BRAF V600-mutant melanoma. However, adding a third targeted agent following disease progression did not show meaningful efficacy; further research is needed to identify other therapeutic targets to circumvent resistance."

Journal • P2 data • Melanoma • Oncology • Solid Tumor • BRAF

PROPEL 2: Study of Infigratinib in Children with Achondroplasia (clinicaltrials.gov) - P2 | N=84 | Completed | Sponsor: QED Therapeutics, Inc. | Active, not recruiting ➔ Completed

Trial completion • Genetic Disorders