On December 3, 2018 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium" or "the Company"), reported that updated data from its Phase 2 trial of Actimab-A was highlighted in a poster presentation at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Actinium Pharmaceuticals, DEC 3, 2018, View Source [SID1234531829]). The Actimab-A Phase 2 trial studied the ARC or Antibody Radiation Conjugate Actinium-225 – lintuzumab, which delivers potent alpha particle radiation to CD33 expressing cells, in patients with untreated AML over the age of 60 that are unfit for induction chemotherapy. Patients received fractionated doses of Ac-225 – lintuzumab on days 1 and day 8. The poster presented at ASH (Free ASH Whitepaper) highlighted data from a second cohort of 27 patients that received 1.5 µCi/kg/fraction.
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Dr. Mark Berger, Actinium’s Chief Medical Officer said, "In this difficult to treat patient population, we are pleased to have observed this level of single-agent activity from Actimab-A with the benefit of minimal extramedullary toxicities. These results strongly support continued development and we have prioritized highly attractive areas that can leverage the strengths of our ARC approach. A major initiative is our Actimab-MDS trial where we have a clear pathway to a pivotal trial established with the FDA for high-risk patients with myelodysplastic syndromes. Another exciting opportunity is via combination trials with agents like venetoclax in the relapsed, refractory AML setting where the apparent synergy of mechanisms can translate to a therapeutic advantage. In addition, we are pursuing other highly-differentiated opportunities for Actimab-A as a single-agent in patients with high unmet needs where the extremely high-potency of an ARC can be used safely at low doses. An example is our novel trial in AML patients with minimal residual disease post-remission."
Overall response rate in this dosing cohort was 22% (6/27) with 3 CRps and 3 CRis. Among responding patients, 2 had adverse cytogenetics and 1 had previous MDS. This data is in addition to previously reported data from 13 patients that were treated at an original dose cohort of 2.0 µCi/kg/fraction where a 69% overall response rate was reported. The dose was lowered to 1.5 µCi/kg/fraction due to myelosuppression lasting longer than 6 weeks, which resulted in a reduction in the incidence of prolonged thrombocytopenia from 46% to 30%.
The median age of patients in this cohort of the Phase 2 trial was 75 (60 -87) with 81% of patients having ECOG performance status of 1 (13/27) or 2 (9/27). Although patients had untreated acute myeloid leukemia (AML), 52% (14/27) of patients had prior hematologic disease with 79% (11/14) having myelodysplastic syndrome (MDS), 14% (2/14) having chromic myelomonocytic leukemia (CMML) and 7% (1/14) having myelofibrosis. A majority of patients had unfavorable cytogenetics with 56% (15/27) having intermediate-risk and 26% (7/27) having high-risk cytogenetics. In addition, patients were evaluated for CD33 splicing polymorphism and responses occurred irrespective of cytogenetic risk category or splicing genotype.
Actinium also highlighted that preliminary preclinical data from its Iomab-ACT program was highlighted in the ASH (Free ASH Whitepaper) supplemental edition of blood. Actinium’s preclinical studies showed a considerable reduction in both lymphocyte and myeloid cell counts, inclusive of immune suppressive regulatory T cells and myeloid derived suppressor cells. Further, the cytoreduction by CD45-RIT was shown to induce the expression of immune homeostatic cytokines including IL-15.The abstract can be accessed he View Source
Sandesh Seth, Actinium’s Chairman and CEO said, "Given the recent and increasing competition in AML, we believe the future development pathways selected by our team strategically differentiate Actinium’s CD33 program in a manner that can maximize value creation. We have done this by focusing on an area with limited or no competition via Actimab-MDS in targeted conditioning. We have also leveraged our AWE or Antibody Radiation Conjugate technology platform to add a different modality, namely targeted radiation, to other areas of unmet or underserved needs as evidenced by our Actimab-A plus Venetoclax combinations and Actimab-A MRD trials. With our lead asset, Iomab-B progressing well in its pivotal trial, the near-pivotal Actimab-MDS program and the Iomab-ACT program for lymphodepletion prior to CAR-T, our multi-asset pipeline will enable our company to build a franchise opportunity in targeted conditioning which is almost singular in the industry."