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    DRUG:

    Erivedge (vismodegib)

    i
    Other names: GDC 0449, GDC-0449, GDC0449, R 3616, R3616, RG3616, RG 3616, RO5450815, RO-5450815, RO 5450815, R-3616, RG-3616
    Company:
    Curis, Roche
    Drug class:
    Hedgehog cell-signalling pathway inhibitor
    Related drugs:
    21d
    A Clinical and Molecular Risk-Directed Therapy for Newly Diagnosed Medulloblastoma (clinicaltrials.gov)
    P2, N=660, Active, not recruiting, St. Jude Children's Research Hospital | Trial completion date: Jan 2028 --> Oct 2031 | Trial primary completion date: Nov 2025 --> Oct 2028
    Trial completion date • Trial primary completion date
    |
    cisplatin • gemcitabine • cyclophosphamide • pemetrexed • vincristine • Erivedge (vismodegib)
    27d
    Mechanistic insights into pharmacokinetic interactions between simvastatin and vismodegib: Implications for optimization of combination therapy in medulloblastoma. (PubMed, Biochem Biophys Res Commun)
    Taken together, these findings establish a mechanistic foundation for a proposed therapeutic optimization strategy: Reducing vismodegib dosing while leveraging its inhibition-driven elevation of simvastatin systemic/tissue exposure, thereby mitigating dose-limiting skeletal toxicity while maintaining anti-tumor efficacy. This mechanism-based strategy provides a clinically actionable framework for pediatric medulloblastoma with urgent unmet therapeutic needs.
    PK/PD data • Journal
    |
    SLCO1B1 (Solute Carrier Organic Anion Transporter Family Member 1B1)
    |
    Erivedge (vismodegib)
    1m
    A case of basal cell nevus syndrome with a SUFU mutation. (PubMed, Dermatol Online J)
    Rarely, this condition is related to a suppressor of fused gene mutation, which occurs downstream from Smoothened, and is unresponsive to Smoothened inhibitors including vismodegib and sonidegib. Genetic testing was negative for patched 1 and patched 2 mutations but positive for a heterozygous suppressor of fused mutation. Patients with basal cell nevus syndrome should be treated with surgical excision, counseled on sun protection, screened and monitored for complications, and treated with vismodegib (if associated with patched 1 mutation) or itraconazole (if associated with suppressor of fused mutation).
    Journal
    |
    PTCH1 (Patched 1) • SUFU (SUFU Negative Regulator Of Hedgehog Signaling)
    |
    Erivedge (vismodegib) • Odomzo (sonidegib) • itraconazole
    2ms
    Solasodine inhibited the proliferation of gastric cancer cells through suppression of Hedgehog/Gli1 signaling. (PubMed, Food Sci Biotechnol)
    Solasodine inhibited the proliferation of AGS and MKN74 gastric cancer cells and regulated cell cycle (Cyclin D1 and p27) and apoptosis (Bax and Bcl-2) markers in a dose-dependent manner, consistent with the Gli1/2 inhibitor Gant61 but not the Smo inhibitor vismodegib...Moreover, solasodine inhibited Gli1 rather than Smo expression in Hh signaling overexpressed Ptch (-/-) MEF cells. Our findings demonstrate that solasodine inhibits gastric cancer proliferation by targeting Hh/Gli1 signaling, underscoring its potential as a potent agent for prevention and/or inhibition of gastric cancer.
    Journal • IO biomarker
    |
    BCL2 (B-cell CLL/lymphoma 2) • CCND1 (Cyclin D1) • SMO (Smoothened Frizzled Class Receptor) • GLI1 (GLI Family Zinc Finger 1) • BAX (BCL2-associated X protein)
    |
    Erivedge (vismodegib)
    2ms
    Phase II Study of Vismodegib in Patients With SMO- or PTCH1-Mutated Tumors: Results From the National Cancer Institute Molecular Analysis for Therapy Choice Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Trial (EAY131) Subprotocol T. (PubMed, JCO Precis Oncol)
    Vismodegib was well tolerated with mainly grade 1-2 toxicities, but it did not meet the primary end point. Select patients with specific SMO and PTCH1 alterations had notable responses, warranting further comprehensive molecular analyses to elucidate resistance mechanisms.
    P2 data • Journal
    |
    PTCH1 (Patched 1) • SMO (Smoothened Frizzled Class Receptor)
    |
    Erivedge (vismodegib)
    2ms
    Establishment of human histiocytic sarcoma organoids dependent on the SHH/YAP pathway. (PubMed, Hum Cell)
    Accordingly, we evaluated the sensitivity of the organoids to the Sonic Hedgehog inhibitor vismodegib and Yes-associated protein 1 inhibitor verteporfin, both of which demonstrated potent in vitro antitumor activity in organoid cultures. This model offers a valuable preclinical platform for investigating the molecular pathology of this rare malignancy and accelerating the development of targeted therapies.
    Journal
    |
    YAP1 (Yes associated protein 1)
    |
    Erivedge (vismodegib) • Visudyne (verteporfin)
    2ms
    NCI-MATCH: Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial) (clinicaltrials.gov)
    P2, N=6452, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026
    Trial completion date • Trial primary completion date
    |
    MSI (Microsatellite instability) • CD4 (CD4 Molecule)
    |
    Opdivo (nivolumab) • Herceptin (trastuzumab) • Mekinist (trametinib) • Xalkori (crizotinib) • Tagrisso (osimertinib) • Gilotrif (afatinib) • Ibrance (palbociclib) • dasatinib • Tafinlar (dabrafenib) • Vitrakvi (larotrectinib) • sunitinib • Kadcyla (ado-trastuzumab emtansine) • Balversa (erdafitinib) • Mektovi (binimetinib) • adavosertib (AZD1775) • Truqap (capivasertib) • Aliqopa (copanlisib) • fexagratinib (ABSK091) • sapanisertib (CB-228) • ipatasertib (RG7440) • taselisib (GDC-0032) • omipalisib (GSK2126458) • ulixertinib (BVD-523) • Erivedge (vismodegib) • Trazimera (trastuzumab-qyyp) • Fakzynja (defactinib) • GSK2636771 • Paletan (pertuzumab biosimilar) • relatlimab (BMS-986016) • ABP 206 (nivolumab biosimilar) • Pertuvia (pertuzumab biosimilar)
    2ms
    RADIOSONIC: Radiotherapy by Sonic Hedgehog Pathway Inhibitors in Basal Cell Carcinoma (clinicaltrials.gov)
    P2, N=82, Recruiting, University Hospital, Lille | Not yet recruiting --> Recruiting | Trial completion date: Jul 2028 --> Jun 2029 | Trial primary completion date: Jul 2028 --> Jun 2029
    Enrollment open • Trial completion date • Trial primary completion date
    |
    Erivedge (vismodegib)
    4ms
    GDC-0449 suppresses odontogenic keratocyst aggressiveness in fibroblasts by upregulating SPARC via Hedgehog pathway inhibition. (PubMed, Arch Oral Biol)
    GDC-0449 suppresses aggressiveness and osteoclastogenesis of OKCs while promoting osteogenesis. GDC-0449 treats OKCs by inhibiting Hh signaling and upregulating SPARC. SPARC could be a potential therapeutic target for OKCs.
    Journal
    |
    PTCH1 (Patched 1) • SPARC (Secreted Protein Acidic And Cysteine Rich) • GLI1 (GLI Family Zinc Finger 1)
    |
    Erivedge (vismodegib)
    6ms
    Vismodegib Combined With Atezolizumab in Platinum Resistant Ovarian, Fallopian Tube, and Primary Peritoneal Cancer (clinicaltrials.gov)
    P2, N=48, Recruiting, Ronald Buckanovich | Trial completion date: Apr 2028 --> Mar 2033 | Trial primary completion date: Apr 2028 --> Mar 2031
    Trial completion date • Trial primary completion date • Platinum resistant
    |
    BRCA (Breast cancer early onset) • CD4 (CD4 Molecule)
    |
    Tecentriq (atezolizumab) • Erivedge (vismodegib)
    6ms
    Prevalence of genetic alterations in basal cell carcinoma patients resistant to Hedgehog pathway inhibitors: a systematic review. (PubMed, Ann Med)
    We included three prospective cohort studies encompassing 27 samples, all of which were resistant to vismodegib treatment...This systematic review highlights the prevalence of genetic alterations in the Hh pathway in BCC and offers insights into the mechanisms involved in treatment resistance. Understanding the high resistance rates of these genes may facilitate the development of more effective targeted therapies for BCC.
    Review • Journal
    |
    TP53 (Tumor protein P53) • PTCH1 (Patched 1)
    |
    TP53 mutation
    |
    Erivedge (vismodegib)
    6ms
    Hedgehog inhibitors exert anti-proliferation effects and synergistically interact with trastuzumab in HER2-positive gastric cancer models. (PubMed, Acta Oncol)
    This study highlights the potential of combining Hh inhibitors with trastuzumab as a therapeutic strategy for HER2-positive GC by targeting the AKT/mTOR pathway.
    Preclinical • Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • SMO (Smoothened Frizzled Class Receptor)
    |
    HER-2 positive
    |
    Herceptin (trastuzumab) • Erivedge (vismodegib) • cyclopamine