Actuate Therapeutics announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to elraglusib, a novel glycogen synthase kinase-3 beta (GSK-3β) inhibitor, for the treatment of soft tissue sarcoma (STS). This designation highlights the potential of elraglusib to address the unmet medical needs of patients with this rare and difficult-to-treat cancer.
Clinical Significance
Soft tissue sarcomas are a heterogeneous group of tumors with over 70 identified subtypes, making treatment challenging. While surgery remains effective for localized disease with median survival approaching 50%, patients with metastatic STS face a poor prognosis, with median overall survival of less than 6-12 months. Current first-line systemic treatment, doxorubicin, has limited antitumor activity, underscoring the urgent need for new therapeutic options.
Elraglusib: A Novel GSK-3β Inhibitor
Elraglusib is designed to target molecular pathways involved in tumor growth and resistance to conventional cancer drugs. Preclinical studies have demonstrated that elraglusib induces significant STS cell apoptosis and synergistic effects with chemotherapy, providing a rationale for its clinical evaluation in metastatic STS.
Daniel Schmitt, President & Chief Executive Officer of Actuate, stated, "We are pleased to receive the ODD from the FDA, which underscores elraglusib’s potential to address the significant yet unmet medical needs for patients with advanced cancers. Elraglusib is a leading GSK-3β inhibitor that has demonstrated a favorable safety profile and antitumor activity across several solid tumors including melanoma, Ewing sarcoma, colorectal and pancreatic cancers. We look forward to the continued development of elraglusib and working closely with regulators to deliver its promise to cancer patients."
Ongoing Clinical Trials
Elraglusib is currently being evaluated in an open-label, two-stratum, phase 2 trial (NCT04906876) in combination with gemcitabine and docetaxel for patients with unresectable or metastatic soft tissue or bone sarcomas. The primary outcome of the study is disease control rate, with progression-free survival (PFS) as a secondary endpoint.
In addition to the phase 2 trial, elraglusib is also being studied as monotherapy and in combination with chemotherapy in a phase 1 study for patients with relapsed/refractory advanced solid tumors or hematologic malignancies. Initial findings from the phase 1 trial established a recommended phase 2 dose (RP2D) of elraglusib at 15 mg/kg twice weekly, later amended to 9.3 mg/kg once weekly to mitigate catheter blockages. The study also reported preliminary evidence of antitumor activity in heavily pretreated patients.
