Actinium Pharmaceuticals said Thursday that the next stage of development for its CD33 ARC (Antibody Radiation Conjugate) Ac-225-Lintuzumab program are pivotal trial pathway for its Actimab-MDS program for Myelodysplastic Syndromes (MDS), and also in two combination trials with Venetoclax for AML.
This comes after successful completion of the Actimab-A phase 2 trial in Acute Myeloid Leukemia (AML), the company said.
The development strategy for Actinium’s CD33 program is being informed by clinical data from 4 trials, the FDA interactions about th eActimab-MDS trial, and its own research findings on the potential synergy with Venetoclax. It also incorporates support from leading physicians; and attractiveness of the targeted indications given the unmet medical need and potential of its differentiated ARC modality in combination with chemotherapy.
The FDA guided for an accelerated pathway to a pivotal trial for the Actimab-MDS program, after a short dose finding Phase 1 portion, as the company was encouraged by the FDA to expand the trial to include all high-risk patients with poor or very poor and complex cytogenetics. According to Actinium, the program will use the ARC Ac-225-lintuzumab for targeted conditioning in combination with a reduced intensity dose of fludarabine and melphalan prior to a BMT or Bone Marrow Transplant in patients with high-risk Myelodysplastic Syndrome (MDS).
Goal is to use its own ARC AC-225 – Lintuzumab to target cells of the myeloid lineage
Dr. Mark Berger, Actinium’s Chief Medical Officer said the company saw in studies that Ac-225 – Lintuzumab can achieve remissions with minimal extramedullary toxicities even in patients progressing to AML from MDS. He said the goal of the Actimab-MDS program is to use its own ARC AC-225 – Lintuzumab to target cells of the myeloid lineage including progenitor cells in combination with reduced intensity conditioning with the goal of achieving improved conditioning and BMT outcomes, as successful BMT is the only potentially curative treatment option for these patients.
“We are building on the data we already have from our CD33 program and we are excited to have a quicker pathway to a pivotal trial that targets a larger patient population than originally envisaged,” said Berger.
Two combination trials with Venetoclax, a BCL-2 inhibitor was jointly developed by AbbVie and Genentech
Actinium’s two combination trials with Venetoclax, a BCL-2 inhibitor that was jointly developed by AbbVie and Genentech, will leverage Actimab-A’s unique and differentiated mechanism of action to explore synergies between the two agents for patients with relapsed or refractory AML. Venetoclax is an approved drug for patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) and a supplemental New Drug Application (NDA) has been submitted to the FDA for patients newly diagnosed with AML.
The first proposed study will evaluate Actimab-A in combination with Venetoclax, while the second study will evaluate Actimab-A in combination with Venetoclax and hypomethylating agents.
The company is pursuing these combination trials with Actimab-A and Venetoclax on the basis of internal preclinical studies which have demonstrated a synergistic effect between these two agents that is supported by a mechanistic rational.