Actinium Announces Positive Phase 3 Trial Results, NCI CRADA For AML Drug Candidates – Could They Become New Standards Of Care For This Deadly Disease?

Patients with relapsed or refractory (r/r) acute myeloid leukemia (AML) have a poor prognosis, and treatment remains challenging. It is a devastating disease that still represents a major unmet medical need, and for the majority of r/r patients, allogeneic hematopoietic stem cell transplantation (HSCT) has been the main curative treatment approach.

Worryingly, the American Cancer Society estimates that about 20,380 new cases of AML will be recorded in the U.S. this year, with most being adults. More disturbingly, approximately 11,310 patients are projected to die from AML this year.

A deeper dive into this unmet medical need paints a bleaker picture. Relapsed or refractory AML is associated with dismal outcomes, and up to 57% of patients experience primary refractory AML, relapse after complete remission (CR), or death in the first 12 months after diagnosis.

The need to advance research to develop effective therapies for patients is driving the growth of the acute myeloid leukemia market. The global market is expected to grow from $1.15 billion in 2022 to $1.29 billion in 2023 at a compound annual growth rate (CAGR) of 12.38%.

While players like Novartis AG NVS, Syndax Pharmaceuticals Inc. SNDX, Kura Oncology KURA, and Pfizer Inc. PFE are advancing therapies for AML, recent pivotal phase 3 results released by Actinium Pharmaceuticals Inc. ATNM could be of interest to patients, the medical community and investors.

New Standards Of Care For r/r AML?

Actinium, a leading company in the development of targeted radiotherapies, announced positive top-line results from its pivotal phase 3 SIERRA Trial. The trial evaluated the efficacy and safety of Iomab-B, a targeted radiotherapy, in patients with r/r AML.

The study enrolled patients aged 55 and above who had active disease or had relapsed after previous treatment, or were refractory to current therapy. The trial was designed to evaluate the efficacy of Iomab-B, compared to the current standard of care, in conditioning patients for an HSCT.

The study’s primary endpoint was to demonstrate a significant improvement in overall survival (OS) for patients receiving Iomab-B compared to those receiving the current standard of care. The trial also evaluated important secondary endpoints, including the rate of durable complete remission (dCR) and the rate of successful HSCT.

Preliminary findings demonstrated that treatment with the company’s novel targeted radiotherapy (Iomab-B) resulted in the disappearance of all signs of cancer from treatment for six months in patients 55 years and older with r/r AML.

Iomab-B is a first-in-class targeted radiotherapy intended to improve patient access to potentially curative bone marrow transplant (BMT) by simultaneously and rapidly depleting blood cancer, immune, and bone marrow stem cells that uniquely express CD45. It is designed to deliver targeted radiation to cancer cells while sparing healthy cells.

The SIERRA trial enrolled 153 patients who were ineligible for a BMT. These patients were randomly assigned to receive either Iomab-B followed by a BMT or the physician’s choice of chemotherapy.

The trial showed that Iomab-B met the primary endpoint of dCR of 6 months following initial complete remission after BMT with high statistical significance (p-value of <0.0001). Additionally, the trial showed that patients treated with Iomab-B had a significantly longer median Overall Survival (OS) than those treated with standard chemotherapy (6.4 months vs. 3.2 months).

“These positive SIERRA results will help to establish Iomab-B as a new standard of care for r/r AML. Iomab-B is a very attractive option for patients due to its excellent safety and strong efficacy profile. It will enable physicians to provide a treatment intervention with potential long-term survival outcomes and will help bring more patients to curative BMTs,” Sandesh Seth, Actinium’s Chairman and CEO, said.

He added that “the lack of current or visible competition for Iomab-B and the concentration of BMT centers imply that successful commercialization of this high-value treatment can be achieved with a streamlined, efficient organization that is sparing to the balance sheet.”

Dr. Sergio Giralt, Deputy Head of the Division of Hematologic Malignancies, Attending Physician, Adult BMT Service at Memorial Sloan Kettering Cancer Center, commented, “I am thrilled to see a high percentage of Iomab-B patients who achieved durable remissions reaching the critical 2-year survival mark. Significant improvement in event-free survival and overall survival, with an excellent safety profile in the SIERRA trial, demonstrate the potential of Iomab-B becoming a new standard of care for active, r/r AML.”

Actinium expects to submit a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for Iomab-B in the second half of 2023. If approved, Iomab-B could become the first targeted radiotherapy to be approved for conditioning prior to HSCT for patients with r/r AML. Iomab-B has already been granted Orphan Drug Designation from the FDA and has patent protection into 2037.

Read the full data results from the Pivotal Phase 3 SIERRA Trial here and view Actinium’s KOL event here.

The company has also been actively working on Actimab-A, another targeted radiotherapy for patients with r/r AML. Iomab-B and Actimab-A product candidates fill the major unmet medical needs in r/r AML in a complementary fashion as they are directed at different parts of the patient journey.

Results from Actinium’s Actimab-A + CLAG-M combination trial were presented at the American Society of Hematology Annual Meeting on December 10, 2022. In this difficult-to-treat r/r AML population, the results demonstrate its high potential with a 1-year survival of 53% and 2-year survival of 32%, which are as much as double what can be expected with currently available therapies, especially in patients who fail prior therapy with Venetoclax, a targeted therapy that is widely used to treat patients with AML. The trial showed an Overall Response Rate (“ORR”) of 65% across all dose cohorts, 52% complete remission rate, and a 75% MRD negativity rate. As highlighted in the figure below, the results are highly encouraging and show that the high rates of responses and MRD negativity are translating to a meaningful survival benefit in these difficult-to-treat patients, who would otherwise have dismal outcomes.

According to Actinium, Actimab-A is a targeted therapy for fit patients that has demonstrated an impressive extension in survival in a proof-of-concept study and is poised for advanced development in collaboration with the National Cancer Institute (NCI). Together, the company believes that Iomab-B and Actimab-A provide a unique opportunity to transform the treatment of AML, especially in the relapsed and refractory segment, representing over 50% of AML patients, as depicted in the graphic below.

The company notes that Actimab-A is the industry-leading program that leverages the potent alpha radiation emitting isotope Actinium-225 (Ac225) based on clinical development in approximately 150 patients treated over six clinical trials.

Commercial Strategy for Iomab-B and Actimab-A 

Actinium’s commercial efforts would be focused on a concentrated point of care; the top 50 transplant centers that account for approximately 75% of BMTs and the top 100 hospitals that treat over 50 percent of r/r AML patients. Further, there is significant overlap in the healthcare providers and ecosystem required to diagnose, treat and care for r/r AML patients within these hospitals, which Actinium believes can be successfully addressed with a relatively small commercial organization of 35-50 people.

(source: Actinium’s Investor Presentation)

In April last year, Actinium and Immedica Pharma entered a license and supply agreement — commercialization agreement — for Iomab-B in Europe, the Middle East and North Africa (MENA).

Under the terms of the agreement, Actinium received an upfront payment of $35 million and is eligible to receive an additional $417 million in regulatory and commercial milestones as well as royalties in the mid-twenty percent range on net sales.

Immedica received commercialization rights in Europe and MENA countries, while Actinium retained all rights related to Iomab-B in the U.S. and the rest of the world. Per the agreement, Actinium will be responsible for certain clinical and regulatory activities and the manufacturing of Iomab-B.

Featured Photo by Michael Jung on Shutterstock

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