Actinium Highlights Mutation Data from the Phase 3 SIERRA Trial of Iomab-B and Novel Linker Technology to Support Solid Tumor Antibody Radiation Conjugate Development at the 2024 Society of Nuclear Medicine & Molecular Imaging Annual Meeting
Actinium Pharmaceuticals presented data from the Phase 3 SIERRA trial of Iomab-B at the 2024 Society of Nuclear Medicine & Molecular Imaging Annual Meeting.
Iomab-B, a CD45 targeting ARC, significantly improved survival for high-risk relapsed or refractory AML patients, including those with TP53 mutations. The trial achieved its primary endpoint of durable Complete Remission with high statistical significance (p<0.0001). Patients receiving Iomab-B had a median OS of 5.49 months compared to 1.66 months for the control group.
Actinium also showcased its novel linker technology, demonstrating high tumor uptake and in vivo stability in preclinical models, with significantly lower kidney and liver uptake compared to standard DOTA linkers. This technology supports the expansion of Actinium's ARC pipeline for solid tumors.
The SIERRA trial involved 153 patients, with Iomab-B delivering targeted radiation more effectively and safely than total body irradiation, while sparing healthy organs.
Actinium has two U.S. patents for its linker technology extending into 2043, with a pending international application.
- Iomab-B achieved durable Complete Remission (dCR) with high statistical significance (p<0.0001).
- Median overall survival (OS) for patients receiving Iomab-B was 5.49 months, compared to 1.66 months for the control arm.
- Iomab-B safely delivers high doses of radiation to diseased bone marrow, sparing healthy organs.
- Actinium's novel linker technology shows high tumor uptake and in vivo stability in preclinical models.
- The novel linker technology demonstrated significantly lower kidney and liver uptake compared to standard DOTA linkers.
- Two U.S. patents for Actinium's linker technology extend into 2043, with a pending international application.
- The median OS for patients with TP53 mutation is still relatively low at 5.49 months.
- The trial's improvements, while significant, are based on a median OS increase from 1.66 to 5.49 months, which may not be deemed sufficient by all stakeholders.
- The highlights primarily focus on preclinical models and early-stage trial results, which may not directly translate to positive outcomes in larger, real-world populations.
Insights
The recent data from the Phase 3 SIERRA trial of Iomab-B presents significant advancements for patients with high-risk relapsed or refractory acute myeloid leukemia (AML), especially those with the TP53 mutation. This mutation is notoriously difficult to treat, often resulting in poor prognoses. The data shows that patients receiving Iomab-B had a median overall survival (OS) of 5.49 months compared to just 1.66 months for those who did not receive this treatment. This suggests that Iomab-B's mechanism of delivering targeted radiation directly to the diseased bone marrow significantly improves patient outcomes compared to traditional therapies.
The ability to deliver higher doses of radiation safely to the bone marrow while sparing non-target organs is a noteworthy improvement. This targeted approach, reflected in the dosimetric analysis, is particularly beneficial in minimizing collateral damage to healthy tissue, thereby reducing side effects and potentially improving the quality of life during treatment.
Furthermore, the novel linker technology shows promise in enhancing the efficacy of targeted radiotherapy for solid tumors. The lower kidney and liver uptake observed with these linkers could help mitigate some of the common adverse effects associated with radiotherapy, making treatments safer and more tolerable for patients.
From an oncological perspective, the data from the SIERRA trial is promising for the treatment landscape of relapsed or refractory AML, particularly for those with the TP53 mutation. Typically, these patients have limited treatment options and poor survival rates. The trial results indicate that Iomab-B can significantly extend survival times, underscoring the potential for this treatment to become a new standard of care for this patient group.
Moreover, the findings on the novel linker technology are encouraging for the future of targeted radiotherapy in solid tumors. By improving tumor uptake and reducing off-target effects, these advancements could lead to more effective therapies with fewer side effects, which is a critical consideration in oncology. The bifunctional linkers’ ability to achieve high tumor concentrations while maintaining stability in vivo points to a potentially impactful development in cancer treatment.
Such improvements in targeted therapy not only enhance treatment efficacy but also offer a better quality of life for patients due to the reduced systemic toxicity. The long-term implications for the oncology field could involve more precise and individualized treatment plans, which aim to maximize treatment benefits while minimizing harm.
Actinium Pharmaceuticals' recent announcements indicate significant potential for growth and market differentiation. The successful Phase 3 trial of Iomab-B, particularly its efficacy in treating patients with TP53 mutations, positions the company as a leader in the niche but critical field of targeted radiotherapy for hematological malignancies. Given the high statistical significance of the primary endpoint, durable Complete Remission (dCR), this treatment could drive substantial revenue growth if approved and adopted widely.
Additionally, the novel linker technology for solid tumor applications could diversify Actinium's portfolio, reducing dependency on a single product line and opening new revenue streams. The reduced uptake in non-target organs suggests a safer profile, which could appeal to both clinicians and patients, potentially accelerating market adoption.
Investors should note the company’s strategic moves towards proprietary manufacturing capabilities with Actinium-225, which could provide a competitive advantage by ensuring a stable supply of high-purity isotopes. This ability to control a critical component of their treatment pipeline might reduce costs and improve margins in the long term.
Overall, Actinium's advancements not only bolster its product pipeline but also enhance its market positioning, making it a compelling entity within the biotech sector.
- Iomab-B led bone marrow transplant improved survival in patients with high-risk relapsed or refractory acute myeloid leukemia including those with a TP53 mutation
- Iomab-B safely delivered radiation to the target bone marrow at greater amounts than achievable with total body irradiation while sparing healthy non-target organs and enabled
100% access to bone marrow transplant - Novel linker technology supports Actinium's Antibody Radiation Conjugate pipeline expansion in solid tumor indications
Actinium's Iomab-B SNMMI presentations and highlights:
Survival Outcomes and Dosimetric Analysis of Iomab-B (131I-apamistamab) Followed by Allogeneic Hematopoietic Cell Transplant for Patients with TP53 Mutated Relapsed/Refractory AML
- 37 patients (
24% ) enrolled on SIERRA had a TP53 mutation with 27 patients receiving Iomab-B (either through randomization or cross over) and 10 patients on the control arm - For patients with TP53 mutation who received Iomab-B, the median OS was 5.49 months compared to a median 1.66 months in pts who did not receive Iomab-B (HR=0.23;
95% CI [0.10, 0.52]) - These results support Iomab-B's differentiated mechanism of action to overcome the negative impact of TP53 mutation typically associated with a dismal prognosis in these patients
Exploratory Analysis of Bone Marrow Dosimetry from the Randomized Phase 3 SIERRA Trial of Iomab-B (131I-apamistamab) Prior to HCT in Relapsed/Refractory Acute Myeloid Leukemia
- Iomab-B safely delivers high doses of myeloablative targeted radiation to the diseased bone marrow at greater amounts than what would be achieved with total body irradiation
- Myeloablative doses were safely delivered to patients irrespective of age, performance status and other metrics
- A median of 16Gy of radiation was delivered to the bone marrow while normal healthy organs received significantly less exposure, including the heart (2.6 Gy), lungs (2.5 Gy), small intestine (2.4 Gy), stomach (3.6 Gy), kidneys (4.1 Gy) and the whole body (3.3 Gy)
Mathematical Modeling of Exposure Measurements Following High-Dose Targeted Therapy Using 131I-apamistamab: Analysis From the Large Multicenter Phase III SIERRA Trial
- SIERRA patients received up to 1,030 mCi (range: 300-1,030) of Iodine-131 via Iomab-B
- Iomab-B is administered via a single infusion 12 days prior to BMT
- Data from SIERRA show that the median time for patients to reach the release criteria was 5 days, including in patients receiving greater than 800 mCi
Actinium's Proprietary Linker Technology SNMMI presentation and highlights:
Evaluation of novel DOTA-based linkers for improved targeted radiotherapy delivery to solid tumors
- Novel linkers showed significantly lower kidney and liver uptake compared to standard DOTA linkers
- SPECT/CT imaging showed high tumor uptake and in vivo stability in preclinical models
- Successful design, efficient conjugation and pharmacological properties support further advancement of these novel linkers
- Actinium has two wholly owned U.S. patents covering its novel bifunctional linker technology with each having a patent term extending into 2043 and a pending international patent application
Sandesh Seth, Actinium's Chairman and CEO, said, "At this year's SNMMI, we are proud to highlight Actinium's broad ARC pipeline and capabilities. Building on our leadership position in hematology focused ARCs through Iomab-B and Actimab-A, we are excited to highlight the potential to treat patients with high-risk relapsed or refractory AML and overcome TP53 mutations or extensive prior therapy including Venetoclax. Hematology represents an area with potential for significant growth for the field of nuclear medicine and there is great excitement from the community around our efforts. Consistent with our vision to build a leading specialty radiotherapeutics company, we are also eager to highlight our novel linker technology for solid tumor ARCs. Finally, SNMMI provides the opportunity to showcase our proprietary Actinium-225 cyclotron-based manufacturing technology that has the potential to produce highly pure medical grade Actinium-225 at a scale and cost that is not currently achievable, which has been met with great enthusiasm given the industry emphasis on Actinium-225 supply."
About the SNMMI Annual Meeting
The SNMMI Annual Meeting is recognized as the premier educational, scientific, research, and networking event in nuclear medicine and molecular imaging. The four-day event, taking place each June, provides physicians, technologists, pharmacists, laboratory professionals, and scientists with an in-depth view of the latest research and development in the field as well as providing insights into practical applications for the clinic.
About Actinium Pharmaceuticals, Inc.
Actinium develops targeted radiotherapies to meaningfully improve survival for people who have failed existing oncology therapies. Advanced pipeline candidates Iomab-B (pre-BLA & MAA (EU)), an induction and conditioning agent prior to bone marrow transplant, and Actimab-A (National Cancer Institute CRADA pivotal development path), a therapeutic agent, have demonstrated potential to extend survival outcomes for people with relapsed and refractory acute myeloid leukemia. Actinium plans to advance Iomab-B for other blood cancers and next generation conditioning candidate Iomab-ACT to improve cell and gene therapy outcomes. Actinium holds more than 230 patents and patent applications including several patents related to the manufacture of the isotope Ac-225 in a cyclotron.
For more information, please visit: https://www.actiniumpharma.com/
Forward-Looking Statements
This press release may contain projections or other "forward-looking statements" within the meaning of the "safe-harbor" provisions of the private securities litigation reform act of 1995 regarding future events or the future financial performance of the Company which the Company undertakes no obligation to update. These statements are based on management's current expectations and are subject to risks and uncertainties that may cause actual results to differ materially from the anticipated or estimated future results, including the risks and uncertainties associated with preliminary study results varying from final results, estimates of potential markets for drugs under development, clinical trials, actions by the FDA and other governmental agencies, regulatory clearances, responses to regulatory matters, the market demand for and acceptance of Actinium's products and services, performance of clinical research organizations and other risks detailed from time to time in Actinium's filings with the Securities and Exchange Commission (the "SEC"), including without limitation its most recent annual report on form 10-K, subsequent quarterly reports on Forms 10-Q and Forms 8-K, each as amended and supplemented from time to time.
Investors:
investorrelations@actiniumpharma.com
View original content to download multimedia:https://www.prnewswire.com/news-releases/actinium-highlights-mutation-data-from-the-phase-3-sierra-trial-of-iomab-b-and-novel-linker-technology-to-support-solid-tumor-antibody-radiation-conjugate-development-at-the-2024-society-of-nuclear-medicine--molecular-imaging-ann-302168214.html
SOURCE Actinium Pharmaceuticals, Inc.
FAQ
What were the results of the Phase 3 SIERRA trial for Iomab-B?
How effective is Iomab-B for TP53 mutated AML patients?
What is Actinium's novel linker technology?
How does Iomab-B compare to total body irradiation?
What are the patent details for Actinium's linker technology?
