Actinium Updates on BLA Filing and Future Iomab-B Plans in U.S.

Actinium Pharmaceuticals, Inc., a prominent developer of Antibody Radiation Conjugates (ARCs) and targeted radiotherapies, has released a regulatory update regarding its Biologics License Application (BLA) for Iomab-B, a treatment for patients with active relapsed or refractory acute myeloid leukemia (r/r AML). Despite achieving statistically significant results in the Phase 3 SIERRA trial, the FDA has concluded that additional clinical evidence demonstrating an overall survival benefit is necessary for the BLA filing.

Iomab-B is a targeted radiotherapy agent composed of an anti-CD45 monoclonal antibody and an Iodine-131 radioisotope payload. Actinium had completed interactions with the FDA concerning both clinical and Chemistry, Manufacturing, and Controls (CMC) aspects of the BLA pathway. The SIERRA trial, which enrolled 153 patients with r/r AML, showed that Iomab-B met its primary endpoint of durable Complete Remission (dCR) with significant statistical relevance (p-value < 0.0001). However, the FDA has stated that a new randomized trial demonstrating overall survival benefits is required for a BLA filing.

The FDA has suggested that the new study should evaluate Iomab-B combined with a reduced-intensity conditioning regimen of fludarabine and total body irradiation (Flu/TBI) against allogeneic bone marrow transplant (BMT) using cyclophosphamide plus Flu/TBI. This is a shift from the SIERRA trial, which allowed physicians to choose salvage therapies and heterogenous conditioning regimens in the control arm. Additionally, the new study will not permit crossover from the control arm, a factor that confounded the overall survival analysis in the SIERRA trial due to nearly 60% of patients crossing over.

Actinium plans to discuss the specifics of the additional trial with the FDA, including the patient population, which may encompass all adult AML patients. Following these discussions, Actinium will seek a strategic partner in the U.S. to further the development of Iomab-B and will focus on other development efforts including Actimab-A, Iomab-ACT, and preclinical programs.

Actinium's Chief Medical Officer, Dr. Avinash Desai, acknowledged the unexpected outcome but expressed determination to work with the FDA to outline the next steps for the proposed trial. He highlighted the extensive interest from the transplant community in better conditioning regimens, as evidenced by 12 oral presentations of the SIERRA results at leading conferences in the U.S. and Europe. Dr. Desai also emphasized the relationships built with key thought leaders during the SIERRA trial, which will be beneficial for future collaborations.

Sandesh Seth, Actinium's Chairman and CEO, voiced disappointment that the SIERRA trial results were not sufficient for a BLA filing despite meeting key endpoints. He noted that the trial demonstrated Actinium's capability in managing manufacturing, supply chain, clinical development, and operations effectively. Seth reiterated the company's commitment to advancing its ARC pipeline and establishing a viable development path for Iomab-B while seeking a strategic partner.

Actinium Pharmaceuticals continues to develop ARCs and other targeted radiotherapies aimed at improving outcomes for patients who have not responded to existing oncology treatments. Alongside Iomab-B, the company is advancing Actimab-A, which has shown potential activity in r/r AML patients, and Iomab-ACT, designed to enhance patient access and outcomes for cell and gene therapies. Actinium holds over 235 patents and is focused on advancing several preclinical programs for solid tumor indications.