Actimab-A extends overall survival, reduces bone marrow blasts in older AML patients

Interim data from an ongoing Phase I/II trial of Actimab-A, an innovative targeted payload immunotherapy, demonstrated a number of positive findings, including extension of overall survival and significant reductions in bone marrow blasts in older patients with newly diagnosed Acute Myeloid Leukemia (AML). Actimab-A is a radiolabeled antibody being developed by New York-based Actinium Pharmaceuticals for newly diagnosed AML in patients over 60, and is currently in a multicenter Phase I/II clinical trial.

Most notably, median overall survival (OS) of secondary AML patients (with prior myelodysplastic syndrome, or MDS) was 9.1 months, which is a substantial prolongation of life versus historical norms, typically 2 to 5 months . Older AML patients are already higher risk, with secondary AML patients considered to have the more severe and less treatable form of AML, and the shortest expected survival. The clinical abstract of the study will be published and available online in Blood, the official Journal of the American Society of Hematology.

"Alpha emitting isotopes can result in more efficient leukemia cell killing without the toxicity of intensive chemotherapy" said Joseph Jurcic, M.D., Professor of Medicine and Director of the Hematologic Malignancies Section of the Hematology/Oncology Division at Columbia University Medical Center, and lead study investigator of the trial. "This study shows that Actimab-A can safely and effectively be combined with low-dose chemotherapy in older AML patients. "Even at this early stage in development, the tolerability of the regimen and promising survival data in this poor-risk population are highly encouraging and support our center's commitment to this program. Because many of these patients cannot tolerate intensive chemotherapy, potentially less toxic treatments such as this are desperately needed."

"The data presented provide further evidence that Actimab-A has substantial clinical activity, including a survival benefit, in the hardest to treat AML patients," said Dragan Cicic MD, Chief Medical Officer of Actinium Pharmaceuticals. "The combination of effectiveness in killing other treatment resistant leukemia cells and limited side effects demonstrated could offer a new hope to patients whose age, comorbidities and nature of disease currently leaves them with very limited treatment options. We continue to work with a world-class team of clinical investigators to ensure the advancement of this program and technology."

This company sponsored trial validates results from the prior three trials in Actinium's HuM195-Alpha Program. The abstract, Phase I Trial of Targeted Alpha-Particle Therapy Using Actinium-225 (225Ac)-Lintuzumab (Anti-CD33) in Combination with Low-Dose Cytarabine (LDAC) for Older Patients with Untreated Acute Myeloid Leukemia (AML) will be published and available online in Blood, the official Journal of the American Society of Hematology.

In this interim analysis, a total of 9 patients were evaluated thus far with a median age of 76 (range 73-81). All had intermediate or poor risk cytogenetics, and 7 of 9 patients had secondary AML as a result of prior MDS. These 7 secondary AML patients had a median OS of 9.1 months from study entry (range 2.3-24 months). Of these, 2 patients lived longer than 12 months and the longest surviving patient lived greater than 24 months. Overall, for all 9 patients median OS was 5.4 months (range 2.2-24 months).

Two dosing levels have been evaluated to date (0.5 or 1.0 μCi/kg/fraction), and the study is ongoing at higher doses until maximum tolerated dose (MTD) is reached, balancing efficacy and safety. Despite not having yet reached MTD, the Company has observed significant bone marrow blast reductions, another important marker of efficacy. Of the 7 evaluable patients in the overall study, 5 patients (71%) had bone marrow blast reductions with a mean of 61% reduction.

The sites participating in this multi-center trial are Memorial Sloan-Kettering, MD Anderson, Johns Hopkins, Columbia University, University of Pennsylvania, Fred Hutchinson and Baylor. The Company expects to announce further information related to Actimab-A development subsequent to its Clinical Advisory Board meeting, during the ASH 2014 time frame (December 6-9, 2014).

Elderly, high risk patients ordinarily have a life expectancy of 5 or fewer months if treated with standard chemotherapy, though only about a third of them do receive treatment because of toxicity. The other two-thirds receive best supportive care, with 2 months survival, according to Oran and Weisdorf (Haematologica 2012; 1916-24). The majority (5 of 7) of the secondary AML patients receiving Actimab-A had been previously treated with hypomethylating agents, a criterion which would have excluded such patients from some other clinical trials. Previous treatment with hypomethylating agents, and subsequent failure, further demonstrates the disease severity of patients in the Actimab-A trial.

The safety profile of Actimab-A remains satisfactory and acceptable for this patient population. The only drug-related serious adverse events (SAEs) seen were related to myelosuppression, which is expected in the treatment of leukemia.

The antibody portion of Actimab-A, HuM195 (also known as lintuzumab) when labelled with alpha particles has been evaluated in three prior studies, including two studies of Bismab-A which was an earlier, first generation construct and an investigator sponsored trial with Actimab-A. Today's interim results mark the first look at clinically meaningful data in the ongoing, Company sponsored Phase I/II trial of Actimab-A.

Secondary AML is a common form of AML in the US, and is defined as AML that develops following exposure to cytotoxic agents or as a subsequent event in another hematologic disorder, usually myelodysplasia (MDS). According to the American Cancer Society there is an annual incidence of 12,000 new cases of MDS in the US. Between 30% and 50% of these new cases go on to develop AML, or approximately 3,600-6,000 secondary AML patients in the US.