Actinium Pharmaceuticals, Inc. announced that results from the Phase 3 SIERRA trial of Iomab-B were presented in an oral presentation at the 65th Annual American Society of Hematology Meeting & Exposition (ASH). The oral presentation highlighted significantly improved survival in patients with a TP53 mutation receiving Iomab-B. Iomab-B is a targeted radiotherapeutic comprised of an anti-CD45 monoclonal antibody with the Iodine-131 radioisotope payload. The Phase 3 SIERRA trial enrolled 153 patients with active relapsed or refractory acute myeloid leukemia (AML) and compared outcomes of patients receiving Iomab-B and a bone marrow transplant (BMT) to those of patients receiving physician's choice of care in the control arm, which was intended to reflect current best practices.

Patients not achieving a Complete Remission (CR) in the control arm who were unable to proceed to a BMT were offered to crossover to receive an Iomab-B led BMT. Iomab-B achieved the primary endpoint in the SIERRA trial of durable Complete Remission (dCR) of at least 6 months with high statistical significance (p<0.0001), with 22% of patients randomized to the Iomab-B arm achieving dCR and 0% of patients in the control arm achieving dCR, irrespective of TP53 mutational status. In addition, Iomab-B significantly improved event-free survival, a secondary endpoint, with a hazard ratio of 0.22 and median overall survival (mOS) was doubled.

Median OS was 6.37 months in TP53 negative patients receiving Iomab-B and 5.72 months for TP53 positive patients demonstrating Iomab-B's ability to overcome TP53 gene mutations. Overall, 24% (37/153) of patients enrolled on SIERRA had a TP53 mutation. In total, 27 patients with a TP53 mutation received Iomab-B and accessed BMT on the SIERRA trial either after initial randomization or following crossover after not being able to access a BMT on the control arm.

Only 1 patient with a TP53 mutation was able to access a BMT on the control arm via conventional care. Iomab-B is a first-in-class targeted radiotherapy intended to improve patient access to potentially curative BMT by simultaneously and rapidly depleting blood cancer, immune and bone marrow stem cells that uniquely express CD45. Multiple studies have demonstrated increased survival in patients receiving BMT, however, an overwhelming majority of patients with blood cancers do not receive BMT as current approaches do not produce a remission, which is needed to advance to BMT, or are too toxic.

Studied in over 400 patients, prior studies with Iomab-B have demonstrated nearly universal access to BMT, increased survival and tolerability in multiple clinical trials including the recently completed pivotal Phase 3 SIERRA trial in patients with active (leukemic blasts >5%), relapsed or refractory acute myeloid leukemia (r/r AML) age 55 and above. Iomab-B met the primary endpoint of durable Complete Remission (dCR) of 6 months after initial remission post-BMT in the pivotal Phase 3 SIERRA trial with high statistical significance (p<0.0001). Iomab-B produced a 75% post-BMT CR rate (44/59 patients), which is 12-times greater than the post-BMT rate of 6.3% (4/64 patients) in the control arm.

Patients receiving Iomab-B had a 78% lower probability of an event, defined as not achieving a CR/CRp, crossover, not receiving a BMT, relapse or death, with a Hazard Ratio of 0.22 (p<0.0001). Iomab-B doubled 1-year overall survival with 26.1% compared to 13.1% in the control arm for patients who did not crossover as well as median overall survival with 6.4 months vs 3.2 months. Overall survival statistics are confounded by the crossover arm.

Crossover patients had a 35.8% 1-year overall survival rate. Due to its targeted nature, Iomab-B was well tolerated with four times lower rates of sepsis compared to the control arm (6.1% vs. 28.6%) and lower rates of BMT associated adverse events including febrile neutropenia, mucositis and graft versus host disease (GVHD).

Actinium intends to submit a Biologics License Application (BLA) seeking approval for Iomab-B in 2024 to address patients age 55+ with r/r AML who cannot access BMT with currently available therapies. Iomab-B has been granted Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) and has patent protection into 2037.