Odomzo (sonidegib) / Sun Pharma, Novartis - LARVOL DELTA

Clinical and Histological Predictors of Advanced Basal Cell Carcinoma Recurrence After Complete Response to Hedgehog Pathway Inhibitors: A Retrospective Multicenter Observational Study. (PubMed, Cancers (Basel)) - "Accordingly, locally advanced BCC histology and time to CR significantly impacted RFS probability. Specific locally advanced BCC histological subtypes and time to CR predict tumor recurrence after CR on HHIs."

Journal • Observational data • Retrospective data • Basal Cell Carcinoma • Genetic Disorders • Non-melanoma Skin Cancer • Skin Cancer • Solid Tumor

Eight-Year Experience of Hedgehog Pathway Inhibitors at Three Tertiary Referral Centres in the Australian State of Victoria. (PubMed, Australas J Dermatol) - "Secondary acquired drug resistance occurred in 77% (10/13) of locally advanced and metastatic BCC patients after a median duration of 13 months. Further work is needed to optimise the neoadjuvant use of Hedgehog inhibitors with radiotherapy or surgery given poor long-term Hedgehog inhibitor tolerability and to develop strategies to counteract the issue of acquired resistance."

Journal • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology

Response to Sonidegib in Advanced Basal Cell Carcinomas by Histological Subtype: A Real-World Cohort. (PubMed, Int J Dermatol) - No abstract available

Journal • Real-world evidence • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology

Docking for Smoothened antagonist chemotypes not susceptible to a vismodegib-resistance mutation. (PubMed, Eur J Med Chem) - "Antagonizing SMO has been recognized as a therapeutic strategy exemplified by drugs such as vismodegib and sonidegib, but despite initial remission, cancer recurrence is frequent due to resistance mutations. The mutation affects potency and maximal inhibitory effect of these ligands only in a way similar to SANT-1, a SMO ligand unencumbered by the mutation. Our study thus shows a successful application of structure-based design for the discovery of novel SMO antagonist chemotypes."

Journal • Oncology

Comparison of the tolerability and safety of hedgehog inhibitors in real-life: A cohort of 330 patients with locally advanced basal cell carcinoma. (ASCO 2025) - "Funded by No funding sources reported Background: Two hedgehog pathway inhibitors (HHIs) have been approved for the treatment of locally advanced basal cell carcinoma (laBCC): vismodegib and sonidegib. We present here the largest real-life comparison of HHIs in a real-life cohort of laBCC patients. The cumulative incidence of the first AE was significantly lower with sonidegib. Even though the range of AEs was similar with both HHIs, dysgeusia and cramps were less frequent with sonidegib."

Clinical • Metastases • Alopecia • Basal Cell Carcinoma • Immunology • Non-melanoma Skin Cancer • Oncology

A phase II, open-label study to improve compliance and time of treatment after obtaining complete response (CR) through a tailored schedule of sonidegib in locally advanced basal cell carcinomas (laBCC): The SONIBEC trial. (ASCO 2025) - P2 | "Tailored maintenance schedule with pulsed sonidegib allows for longer treatment duration and fewer relapses in CR laBCC pts. Study follow up to evaluate secondary endpoints outcome and translational analysis are ongoing. Patient characteristics."

Clinical • Compliance • Metastases • P2 data • Alopecia • Basal Cell Carcinoma • Immunology • Non-melanoma Skin Cancer • Oncology

Blue-Light Photodynamic Therapy and Sonidegib for Multiple Basal Cell Carcinomas (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: Nathalie Zeitouni | Not yet recruiting ➔ Recruiting

Enrollment open • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology

Pityriasis rubra pilaris with symmetric polyarthralgia and lymphadenopathy (SID 2025) - "Proposed treatments include immunomodulators, acitretin, methotrexate and isotretinoin...He also had an impressive response to sonidegib, with shrinking of the large BCC tumors on his back, which were subsequently excised via Mohs...Regarding treatment of the patient's joint pain, the patient was continued on ixekizumab and started on celecoxib as needed for pain. PRP-associated arthritis is a rare component of the primarily dermatologic disorder, and it is important for clinicians to be aware of this association to adequately address joint manifestations. When applicable, paraneoplastic PRP should be explored, and underlying neoplasms should be treated."

Genetic Disorders • Immunology • Inflammatory Arthritis • Musculoskeletal Diseases • Musculoskeletal Pain • Non-melanoma Skin Cancer • Pain • Rheumatology • Skin Cancer • Solid Tumor • IL17A

Hyaluronan-decorated-phloroglucinol-loaded mesoporous silica downregulates GLI1 and SMO genes of hedgehog signaling pathway in gastrointestinal cancer stem-like cells. (PubMed, Int J Biol Macromol) - "Furthermore, the expression analysis utilizing inhibitors such as GANT-61 (GLI1 inhibitor) and Sonidegib (SMO inhibitor) have demonstrated that the MSN-PG-HA has shown a significant level of inhibition as that of GANT-61, indicating a similarity in their mechanism of action in inhibiting the cancer cell proliferation. Thus, our findings conclude that MSN-PG-HA could serve as a potential drug for targeting GI cancer stem cells."

Journal • Gastrointestinal Cancer • Oncology • Solid Tumor • GLI1 • MSN • SMO

Alterations of Ceramide Synthesis Induce PD-L1 Internalization and Signaling to Regulate Tumor Metastasis and Immunotherapy Response (IMMUNOLOGY 2025) - "While mammary tumors developed in MMTV-PyMT/CerS4-/- were highly metastatic, targeting the Shh/PD-L1 axis using Sonidegib and anti-PD-L1 antibody vastly decreased tumor growth and metastasis, consistent with the inhibition of PD-L1 internalization and Shh/Wnt signaling, restoring anti-tumor immune response...Our recent and unpublished data also revealed that attenuation of CerS4 expression and increased intracellular PD-L1 signaling in TNBC tumors result in resistance to anti-PD-1 or anti-PD-L1-based immunotherapy in TNBCs. Inhibition of intracellular PD-L1 signaling resensitized resistant TNBCs in vivo.Keywords: Cells T Cells; Molecules Cell Surface Molecules Lipid Mediators; Processes Signal Transduction; Techniques/Approaches Transgenic/Knockout Mice"

IO biomarker • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CAPRIN1 • CERS4 • FOXP3 • PD-L1 • TGFBR1

Efficacy and Safety of Hedgehog Inhibitors for Advanced Basal Cell Carcinoma: An Expert Consensus Panel. (PubMed, J Drugs Dermatol) - "Sonidegib and vismodegib are FDA-approved HHIs that can decrease the size of laBCC tumors prior to surgical intervention or be used as primary therapy in certain circumstances. The most common adverse events include muscle spasms, alopecia, and taste alterations."

Journal • Alopecia • Basal Cell Carcinoma • Dermatology • Immunology • Non-melanoma Skin Cancer • Oncology

Current treatment options for locally advanced and metastatic basal cell carcinoma. A narrative review. (PubMed, Expert Rev Anticancer Ther) - "Several management options are possible, varying from supportive therapy without any therapeutic intervention until anti-programmed cell death protein-1 (PD-1) immunotherapy, such as cemiplimab, either administered intravenously or intralesional. In between this spectrum, oral hedgehog inhibitors including vismodegib and sonidegib, electrochemotherapy, different types of radiotherapy, and surgery can be considered...The management of laBCC and mBCC patients is determined by a multidisciplinary dermato-oncology board, including dermatologists, medical oncologists, radiotherapists, pathologists, and surgeons, as well as the patient's GP. Today, experts recommend keeping as long as possible laBCC and mBCC patients under sequential courses of HHIs, if surgery and/or radiotherapy are not amenable."

Journal • Review • Basal Cell Carcinoma • Dermatology • Genetic Disorders • Non-melanoma Skin Cancer • Oncology • Skin Cancer

UF-GI-015: AD HOC Trial: Artificial Intelligence-Based Drug Dosing In Hepatocellular Carcinoma (clinicaltrials.gov) - P2 | N=12 | Recruiting | Sponsor: University of Florida | Phase classification: P1 ➔ P2

Phase classification • Hepatocellular Cancer • Oncology • Solid Tumor

Hedgehog signaling pathway inhibitors in the treatment of basal cell carcinoma: An Updated Review. (PubMed, J Drug Target) - "In this review, we summarize BCC's clinical presentation and histopathology and present knowledge on the most studied Hh signaling inhibitors, vismodegib and sonidegib, and other inhibitors of this signaling, such as itraconazole, patidegib, taladegib, and arsenic trioxide, in the treatment of BCC. We also present the most common Hh signaling inhibitor adverse events and their management options, which could improve patients' quality of life during treatment."

Journal • Review • Basal Cell Carcinoma • Genetic Disorders • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Skin Nodular Basal Cell Carcinoma

Efficacy following discontinuation of sonidegib 200 mg daily treatment in patients with locally advanced basal cell carcinoma: Post hoc analysis of the 42-month BOLT study. (PubMed, J Am Acad Dermatol) - No abstract available

Journal • Retrospective data • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology

How the use of sonidegib beyond clinical complete response impacts tolerability in locally advanced basal cell carcinoma: A retrospective monocentric analysis. (PubMed, Clin Exp Dermatol) - No abstract available

Journal • Retrospective data • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology

Patient with Gorlin Syndrome and type 2 mosaicism successfully treated with sonidegib (EADO-WCM 2025) - "Both vismodegib and sonidegib have been shown to be effective, with objective response rates in approximately 60% of patients.[2] Long-term treatment is needed, and side effects often require alternative dosing schedules to improve tolerability. We present a young patient with GS with rapid clinical and cosmetic benefit and good tolerability after treatment with sonidegib. Further studies are needed to establish dosing schedules that will optimize long-term benefit and tolerability."

Clinical • Alopecia • Basal Cell Carcinoma • Eye Cancer • Immunology • Oncology • Skin Cancer

Identification of RCC2 as a Risk Gene Associated With Basal Cell Carcinoma and Experimental Validation. (PubMed, Exp Dermatol) - "While the sonic hedgehog (SHH) signalling pathway and mutations in PTCH1/2 and SMO are well-established drivers of BCC pathogenesis, novel genetic factors may complement existing therapeutic targets such as vismodegib and sonidegib. We identified a risk gene RCC2 associated with BCC by MR-based bioinformatics analysis and demonstrated that inhibition of RCC2 inhibited the proliferation of A431 in vitro. These findings provide new strategies for targeted therapy of BCC."

Journal • Basal Cell Carcinoma • Genetic Disorders • Non-melanoma Skin Cancer • Oncology • Skin Cancer • PTCH1 • SMO

Oral Hedgehog Inhibitors in the Treatment of Basal Cell Carcinoma in the Netherlands: a Prospective Registration Study (clinicaltrials.gov) - P=N/A | N=80 | Recruiting | Sponsor: Maastricht University Medical Center | Trial completion date: Dec 2024 ➔ Dec 2026 | Trial primary completion date: Dec 2024 ➔ Jun 2026

Trial completion date • Trial primary completion date • Basal Cell Carcinoma • Genetic Disorders • Non-melanoma Skin Cancer • Oncology • Rare Diseases • Skin Cancer • Solid Tumor

Evidence on the Use of Sonidegib as Neoadjuvant Therapy in real practice in Spain: A multicenter case series (EADO-WCM 2025) - "The use of sonidegib and vismodegib in reducing tumor size in patients with advanced BCC, allowing less radical surgeries and improving cosmetic and functional outcomes, has previously been highlighted. These treatments might facilitate less extensive surgeries and improve cosmetic and functional outcomes. Further studies with larger sample sizes and long-term follow-up are warranted to fully establish the benefits and risks of neoadjuvant hedgehog inhibitor therapy."

Clinical • Alopecia • Basal Cell Carcinoma • Immunology • Non-melanoma Skin Cancer • Oncology

Sonidegib Inhibits the Adhesion of Acute Myeloid Leukemia to the Bone Marrow in Hypoxia: An Optical Tweezer Study. (PubMed, Biomedicines) - "Additionally, we showed that sonidegib is particularly effective at hypoxic oxygen concentrations. The results obtained in this study suggest that sonidegib, through its modulation of the Hedgehog signaling pathway, holds promise as a potential therapeutic approach to target leukemic cell adhesion within the bone marrow microenvironment."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

3-Oxabicyclo[3.1.1]heptane as an Isostere for meta-Benzene. (PubMed, Angew Chem Int Ed Engl) - "Crystallographic analysis revealed that these structures and meta-benzene have identical geometric properties. Replacement of the central benzene ring in the anticancer drug Sonidegib with 3-oxabicyclo[3.1.1]heptane provided a patent-free analogue with a nanomolar potency, reduced lipophilicity and improved water solubility (>500%)."

Journal • Oncology

Locally advanced basal cell carcinoma treated with sonidegib: in vivo monitoring with line-field confocal optical coherence tomography. (PubMed, Skin Health Dis) - "Hedgehog pathway inhibitors, including sonidegib and vismodegib, represent the treatment strategy for 'difficult-to-treat' basal cell carcinoma (BCC), encompassing, among others, locally advanced (laBCC) and metastatic BCC. Ten patients were continuing sonidegib treatment: in this group LC-OCT revealed findings suggestive of BCC persistence in all 10 patients (100%). In this study we provide preliminary results of the beneficial use of LC-OCT in the management of patients with laBCC treated with sonidegib therapy."

Journal • Preclinical • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology

Managing Advanced Basal Cell Carcinoma: A Guide for the Dermatology Clinician. (PubMed, J Clin Aesthet Dermatol) - "A comprehensive literature search was completed using the keywords "advanced basal cell carcinoma," "treatment," "hedgehog inhibitor," "vismodegib," "sonidegib," "PD1-inhibitor," and "cemiplimab." The authors reviewed all studies and included those which addressed the topic of the review. Treatment of advanced BCCs can be complex and poses challenges for clinicians. HHIs are currently the first-line treatments for laBCC and mBCC, while cemiplimab can be used if patients do not respond to or are unable to tolerate HHIs, or for whom HHIs are not appropriate."

Journal • Review • Basal Cell Carcinoma • Dermatology • Genetic Disorders • Non-melanoma Skin Cancer • Oncology • Skin Cancer

Systemic SMO-Hedgehog inhibition with Sonidegib: real-life experience of the Dermatology Unit of University of Pisa (EADO-WCM 2025) - "If not possible, other approaches include radiotherapy, cryotherapy, topical treatments (like imiquimod cream) and systemic therapy. SMO-Hedgehog-inhibitor drugs, sonidegib and vismodegib, are used for difficult-to-treat BCCs (locally advanced, multiple or metastatic forms)...From our experience, it is a safe and well-manageable drug that gives patients a complete response or the chance to do a less invasive surgical procedure. Its use in patients with multiple BCCs could also avoid a lot of surgeries, reducing costs and improving the quality of life."

Clinical • Basal Cell Carcinoma • Dermatology • Genetic Disorders • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor