Actuate Therapeutics, Inc. has announced that the U.S. Food and Drug Administration (FDA) has granted Rare Pediatric Disease Designation to elraglusib for the treatment of Ewing sarcoma (EWS). Elraglusib is a novel glycogen synthase kinase-3 beta (GSK-3β) inhibitor currently in Phase 1/2 clinical trials.
Clinical Trial Data and Significance
According to Actuate, early clinical data from their ongoing Phase 1/2 trial (NCT 04239092) demonstrates promising anti-tumor activity. The trial, referred to as Actuate-1902, is evaluating the safety and efficacy of elraglusib in pediatric patients with relapsed/refractory malignancies, including EWS and EWS-related pediatric small round cell sarcomas. The data includes objective tumor responses, with two ongoing durable Complete Responses (CRs) observed in the first six patients treated with relapsed/refractory EWS. These patients were treated with a combination of elraglusib and topotecan/cyclophosphamide after experiencing more than one remission.
Daniel Schmitt, President & Chief Executive Officer of Actuate, stated, "Receiving rare pediatric disease designation from the FDA underscores the urgent need for new treatment options for patients with EWS and recognizes elraglusib’s transformative potential."
Ewing Sarcoma: An Unmet Need
Ewing sarcoma is a highly metastatic bone cancer primarily affecting children and adolescents, with a peak incidence around age 15. It is the second most prevalent primary malignant bone tumor in this age group. Approximately 25% of patients have metastatic disease at initial diagnosis, which is a significant predictor of poor survival outcomes. The current standard of care often involves aggressive chemotherapy regimens, surgery, and radiation therapy, which can have significant long-term side effects. New therapeutic options are needed to improve outcomes and reduce treatment-related toxicities.
Regulatory Implications
The Rare Pediatric Disease Designation is granted for diseases affecting fewer than 200,000 people in the U.S., where the serious or life-threatening manifestations primarily affect individuals under 18. If elraglusib receives FDA approval for EWS, Actuate Therapeutics will be eligible for a Priority Review Voucher (PRV). This voucher can be used by Actuate or sold to another company, potentially accelerating the review process for a different drug application.
Elraglusib Mechanism of Action
Elraglusib is designed to target molecular pathways involved in tumor growth and resistance to conventional cancer drugs. It acts as a mediator of anti-tumor immunity through the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and regulates multiple immune checkpoints and immune cell function. The drug also targets several DNA Damage Response (DDR) pathways.
