Actinium Pharmaceuticals Announces Publication of Results from the Phase 3 SIERRA Trial of Iomab-B in the Journal of Clinical Oncology
Actinium Pharmaceuticals (NYSE AMERICAN: ATNM) announced the publication of Phase 3 SIERRA trial results for Iomab-B in the Journal of Clinical Oncology. The trial, involving 153 patients aged 55+ with relapsed/refractory Acute Myeloid Leukemia (r/r AML), compared Iomab-B with bone marrow transplant (BMT) to standard chemotherapy and BMT. Key findings include:
1. Primary endpoint of durable Complete Remission achieved (p<0.0001)
2. Significant improvement in Event-Free Survival (p<0.0001)
3. Overall survival endpoint not met due to high crossover rate
4. Improved outcomes for patients with TP53 mutation and those aged 65+
Despite positive results, the FDA requires an additional Phase 3 trial demonstrating overall survival benefit for BLA filing. Actinium plans to seek a strategic partner for Iomab-B's further development in the U.S.
Actinium Pharmaceuticals (NYSE AMERICAN: ATNM) ha annunciato la pubblicazione dei risultati della fase 3 dello studio SIERRA per Iomab-B sulla rivista Journal of Clinical Oncology. Lo studio, che ha coinvolto 153 pazienti di età superiore ai 55 anni con leucemia mieloide acuta relapsata/rifrazionata (r/r AML), ha confrontato Iomab-B con il trapianto di midollo osseo (BMT) rispetto alla chemioterapia standard e BMT. I risultati chiave includono:
1. L'obiettivo primario di remissione completa duratura raggiunto (p<0.0001)
2. Miglioramento significativo nella sopravvivenza libera da eventi (p<0.0001)
3. Obiettivo di sopravvivenza complessiva non raggiunto a causa dell'alto tasso di crossover
4. Risultati migliorati per i pazienti con mutazione TP53 e per quelli di età superiore a 65 anni
Nonostante i risultati positivi, la FDA richiede un ulteriore studio di fase 3 per dimostrare un beneficio nella sopravvivenza complessiva per la richiesta di BLA. Actinium prevede di cercare un partner strategico per il successivo sviluppo di Iomab-B negli Stati Uniti.
Actinium Pharmaceuticals (NYSE AMERICAN: ATNM) anunció la publicación de los resultados del ensayo de fase 3 SIERRA para Iomab-B en el Journal of Clinical Oncology. El ensayo, que involucró a 153 pacientes de 55 años o más con leucemia mieloide aguda en recaída/resistente (r/r AML), comparó Iomab-B con trasplante de médula ósea (BMT) y quimioterapia estándar más BMT. Los hallazgos clave incluyen:
1. Se alcanzó el objetivo primario de remisión completa duradera (p<0.0001)
2. Mejora significativa en la supervivencia libre de eventos (p<0.0001)
3. El objetivo de supervivencia global no se alcanzó debido a la alta tasa de cruce
4. Mejores resultados para pacientes con mutación en TP53 y aquellos de 65 años o más
A pesar de los resultados positivos, la FDA requiere un ensayo adicional de fase 3 que demuestre un beneficio en la supervivencia global para la presentación de BLA. Actinium planea buscar un socio estratégico para el desarrollo futuro de Iomab-B en EE. UU.
액티니움 제약(뉴욕증권거래소 AMERICAN: ATNM)은 SIERRA 3상 시험 결과를 Clinical Oncology 저널에 발표했다고 발표했습니다. 이 시험은 재발성/내성 급성 골수성 백혈병(r/r AML)을 가진 55세 이상 환자 153명을 포함하여 Iomab-B와 표준 화학요법 및 골수 이식(BMT)을 비교했습니다. 주요 발견 사항은 다음과 같습니다:
1. 지속적인 완전 관해의 주요 목표 달성 (p<0.0001)
2. 무사건 생존의 유의미한 개선 (p<0.0001)
3. 높은 크로스오버 비율로 인해 전체 생존 목표 미달성
4. TP53 변이가 있는 환자 및 65세 이상의 환자의 결과 개선
긍정적인 결과에도 불구하고 FDA는 BLA 제출을 위한 전체 생존 이점을 입증하는 추가 3상 시험을 요구합니다. 액티니움은 Iomab-B의 미국 내 추가 개발을 위한 전략적 파트너를 찾을 계획입니다.
Actinium Pharmaceuticals (NYSE AMERICAN: ATNM) a annoncé la publication des résultats de l'essai de phase 3 SIERRA pour Iomab-B dans le Journal of Clinical Oncology. L'essai, impliquant 153 patients âgés de 55 ans et plus atteints de leucémie myéloïde aiguë en rechute/résistante (r/r AML), a comparé Iomab-B avec une greffe de moelle osseuse (BMT) à une chimiothérapie standard et BMT. Les principaux résultats incluent:
1. Objectif principal de rémission complète durable atteint (p<0.0001)
2. Amélioration significative de la survie sans événement (p<0.0001)
3. Le critère d'évaluation de la survie globale n'a pas été atteint en raison d'un taux de croisement élevé
4. Résultats améliorés pour les patients avec mutation TP53 et ceux âgés de 65 ans ou plus
Malgré des résultats positifs, la FDA exige un essai de phase 3 supplémentaire démontrant un avantage en matière de survie globale pour le dépôt de BLA. Actinium prévoit de rechercher un partenaire stratégique pour le développement futur d'Iomab-B aux États-Unis.
Actinium Pharmaceuticals (NYSE AMERICAN: ATNM) hat die Veröffentlichung der Ergebnisse der Phase 3 SIERRA-Studie für Iomab-B im Journal of Clinical Oncology angekündigt. Die Studie umfasste 153 Patienten ab 55 Jahren mit wiederaufgetretener/resistenter akuter myeloischer Leukämie (r/r AML) und verglich Iomab-B mit einer Knochenmarktransplantation (BMT) und einer Standardchemotherapie plus BMT. Die wichtigsten Ergebnisse umfassen:
1. Primäres Ziel der dauerhaften kompletten Remission erreicht (p<0.0001)
2. Signifikante Verbesserung des ereignisfreien Überlebens (p<0.0001)
3. Ziel des Gesamtüberlebens aufgrund einer hohen Kreuzungsrate nicht erreicht
4. Verbesserte Ergebnisse für Patienten mit TP53-Mutation und für Patienten über 65 Jahren
Trotz positiver Ergebnisse verlangt die FDA eine zusätzliche Phase-3-Studie, die einen Überlebensvorteil zum Zeitpunkt der BLA-Einreichung nachweist. Actinium plant, einen strategischen Partner für die weitere Entwicklung von Iomab-B in den USA zu suchen.
- Iomab-B achieved primary endpoint of durable Complete Remission with high statistical significance (p<0.0001)
- Significant improvement in Event-Free Survival, a secondary endpoint (Hazard Ratio = 0.22, p<0.0001)
- Improved survival outcomes in patients with TP53 mutation and increased 1- and 2-year overall survival in patients aged 65 and above
- Results published in peer-reviewed Journal of Clinical Oncology, enhancing credibility
- SIERRA trial did not meet the secondary endpoint of overall survival on an intent to treat basis
- FDA requires an additional Phase 3 randomized trial demonstrating overall survival benefit for BLA filing
- SIERRA trial alone will not be adequate for BLA filing, potentially delaying market entry
- Company needs to secure a U.S. partner for Iomab-B's further development, adding uncertainty
The publication of the SIERRA trial results in the Journal of Clinical Oncology is a significant milestone for Iomab-B. The trial demonstrated statistically significant improvements in durable Complete Remission (
However, the FDA's requirement for an additional trial to demonstrate overall survival benefit is a setback. This decision likely stems from the high crossover rate (
While the SIERRA trial results are promising, the FDA's decision for an additional trial is a significant hurdle for Actinium. This development will likely impact the company's financial outlook and timeline to market. Key considerations:
- Increased R&D expenses for the new trial
- Delayed potential revenue stream from Iomab-B
- Need for additional funding or strategic partnerships
The search for a U.S. partner for Iomab-B's development could be important for Actinium's financial stability. Investors should closely monitor the company's cash position and any potential partnership announcements, as these factors will be critical for Actinium's long-term viability and the future of Iomab-B.
The FDA's requirement for an additional trial to demonstrate overall survival benefit is not uncommon, especially when crossover designs complicate survival analyses. This decision underscores the agency's focus on robust evidence of clinical benefit, particularly for novel therapies like Iomab-B. Key regulatory implications:
- Longer regulatory pathway to approval
- Need for careful trial design to address FDA concerns
- Potential for accelerated approval pathways if strong interim data is generated
Actinium's engagement with the FDA to finalize the new trial design will be crucial. The company should consider exploring potential accelerated approval options based on surrogate endpoints, which could provide a faster route to market while conducting the confirmatory survival trial.
- Iomab-B is the first CD45 targeted radiotherapy for conditioning in development to enable potentially curative bone marrow transplant and represents an alternative to chemotherapy-based approaches
- SIERRA achieved durable Complete Remission primary endpoint and Event-Free Survival secondary endpoint with high statistical significance
- Iomab-B was well tolerated in the older, heavily pretreated relapsed/refractory AML patients with active disease enrolled in the SIERRA trial
- Actinium to seek strategic partner for Iomab-B for further development in the
U.S. following completion of interactions with FDA for additional head-to-head clinical trial to demonstrate overall survival benefit
The Phase 3 SIERRA (Study of Iomab-B in Elderly Relapsed Refractory AML) trial was a randomized, multi-center, controlled trial that enrolled 153 patients aged 55 and above with active relapsed or refractory Acute Myeloid Leukemia (r/r AML), including heavily pre-treated patients and those with high-risk characteristics such as a TP53 mutation. The SIERRA trial compared outcomes of patients receiving Iomab-B (Iodine-131-apamistamab) and a bone marrow transplant (BMT) to physician's choice of salvage chemotherapy and standard allogeneic BMT in the control arm.
The SIERRA trial met the primary endpoint of durable Complete Remission (dCR) of 6-months following initial complete remission after BMT with high statistical significance (p-value of <0.0001) with
The Phase 3 SIERRA results were first presented in a late-breaker presentation at the Transplantation & Cellular Therapy (TCT) Tandem Meetings of the American Society for Transplantation and Cellular Therapy (ASTCT) and the Center for International Blood & Marrow Transplant Research (CIBMTR) in February 2023. Since TCT, the results of the SIERRA trial have been presented in several oral presentations at leading BMT, hematology, nuclear medicine and nursing meetings and congresses in the
Dr. Sergio Giralt, Deputy Division Head, Division of Hematological Malignancies and Attending Physician, Adult BMT Service at the Memorial Sloan Kettering Cancer Center, and leading SIERRA Trial investigator and corresponding author, said, "The SIERRA trial was important for the field of transplant and demonstrated for the first time in a randomized study that the CD45 antibody-radioconjugate Iomab-B can provide patients with improved access to a potentially curative hematopoietic stem cell transplant, and improved outcomes compared to current chemotherapy-based regimens. Importantly, Iomab-B demonstrated a statistically significant improvement in key efficacy endpoints including durable Complete Remission and event-free survival. The SIERRA trial was conducted as multiple new therapies gained approval and was designed to address the nuances and difficulty of treating this patient population including allowing physician's choice of care in the control arm given the heterogeneity of treatment across institutions and the crossover design to provide best patient care. Despite multiple drug approvals for patients with AML, there remains no curative options for older patients with relapsed or refractory disease and outcomes for these patients also remain dismal. My fellow investigators and I are disappointed that the SIERRA trial will not support the approval of Iomab-B despite the positive results and significant unmet medical need of this patient population. However, there is continued significant interest from the transplant community to participate in the upcoming phase 3 study with Iomab-B to provide patients access to this important drug candidate."
On August 05, 2024, Actinium announced that after concluding both its clinical and Chemistry, Manufacturing and Controls ("CMC") interactions with the FDA regarding the BLA pathway for Iomab-B, the FDA determined that demonstrating an overall survival benefit in a randomized head-to-head trial is required for a BLA filing, and the SIERRA trial alone will not be adequate for BLA filing.
Sandesh Seth, Actinium's Chairman and CEO, stated, "We are excited that the SIERRA results have been published in the peer-reviewed Journal of Clinical Oncology. We believe the SIERRA trial was a major advancement for the field of BMT and targeted radiotherapeutics but most importantly for patients with relapsed and refractory AML. We look forward to completing our interactions with the FDA to finalize the specifics of the additional Phase 3 randomized trial and working to secure a
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, 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.
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