- FDA determined that the Phase 3 SIERRA trial is not adequate to
support a BLA filing for Iomab-B despite its statistically
significant primary endpoint
- Additional head-to-head randomized clinical trial demonstrating
overall survival benefit with Iomab-B is required by FDA to support
a BLA filing
- Actinium to request a meeting with the FDA to further discuss
specifics of additional trial
- Actinium will seek strategic partner for Iomab-B in the U.S.
following completion of FDA interactions and focus development
efforts on Actimab-A, Iomab-ACT and preclinical programs
NEW
YORK, Aug. 5, 2024 /PRNewswire/ -- Actinium
Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium" or the
"Company"), a leader in the development of Antibody Radiation
Conjugates ("ARCs") and other targeted radiotherapies, today
announced a regulatory update on the Company's planned Biologics
License Application ("BLA") filing for Iomab-B in patients with
active relapsed or refractory acute myeloid leukemia ("r/r AML").
Iomab-B is an induction and conditioning targeted radiotherapy
agent comprised of an anti-CD45 monoclonal antibody and Iodine-131
radioisotope payload. The Company announced that it has now
concluded both its clinical and Chemistry, Manufacturing and
Controls ("CMC") interactions with the FDA regarding the BLA
pathway for Iomab-B. Despite the SIERRA trial meeting the primary
endpoint of durable Complete Remission ("dCR") with statistical
significance (p-value<0.0001) and other positive secondary
endpoints including Event Free Survival ("EFS") and safety, the FDA
has now determined that demonstrating an overall survival benefit
in a randomized head-to-head trial is required for a BLA filing.
The FDA has advised Actinium to conduct a study to evaluate
allogeneic bone marrow transplant ("BMT") using Iomab-B plus a
reduced intensity conditioning regimen of fludarabine and total
body irradiation ("Flu/TBI") versus allogeneic BMT using reduced
intensity conditioning comprised of cyclophosphamide plus Flu/TBI,
a difference from the SIERRA trial, which had allowed physician's
choice of salvage therapies and heterogenous conditioning regimens
in the control arm. Additionally, the proposed new study will not
allow patients to crossover from the control arm which was allowed
in the SIERRA trial and confounded the overall survival analysis in
the intent to treat ("ITT") patient population, as nearly 60% of
patients crossed over from the control arm.
The Phase 3 SIERRA trial enrolled 153 patients with r/r AML and
compared outcomes of patients receiving Iomab-B and BMT to patients
receiving physician's choice of care with salvage chemotherapy and
standard allogeneic BMT in the control arm. In February 2023, Actinium announced that the SIERRA
trial met the primary endpoint with statistical significance as 22%
of patients (13/76) on the Iomab-B arm achieved dCR compared to 0%
of patients (0/77) on the control arm resulting in a p-value of
<0.0001. The SIERRA trial was conducted in accordance with
guidance from the End of Phase 2 meeting with the FDA, which stated
that positive results for dCR as the primary endpoint would be an
acceptable endpoint to support an Iomab-B BLA filing. SIERRA did
not meet the secondary endpoint of overall survival on an intent to
treat basis analysis due to the high crossover rate with nearly 60%
of control arm patients receiving Iomab-B followed by a BMT. Over
the last several years, a majority of therapies for patients with
AML have been approved based on achieving a positive overall
survival endpoint.
Actinium presented several additional analyses from the SIERRA
study to the FDA including long-term follow-up that demonstrated a
trend towards improved overall survival and evidence of survival
benefit in patients with high-risk TP53 mutations to support
Iomab-B's impact on overall survival. The SIERRA trial data were
presented in 12 oral presentations at several leading bone marrow
transplant, hematology and nuclear medicine conferences in both the
U.S. and Europe, which Actinium
believes demonstrates the high unmet medical need and scientific
importance of Iomab-B's ability to provide improved access and
outcomes for patients with active r/r AML to the transplant
community. However, the FDA has now determined that the analyses
from the SIERRA trial do not adequately support a BLA filing for
Iomab-B and requires an additional clinical study. Actinium expects
the safety and efficacy data from the SIERRA trial will provide
supportive evidence for a future Iomab-B BLA filing.
Key Outcomes and Implications of FDA Interactions
- Phase 3 SIERRA trial results are not adequate to support a BLA
filing for Iomab-B in patients with active r/r AML
- FDA is requiring an additional randomized head-to-head trial to
demonstrate an overall survival benefit evaluating allogeneic BMT
using Iomab-B plus a reduced intensity conditioning regimen of
fludarabine and total body irradiation (Flu/TBI) to allogeneic BMT
using reduced intensity conditioning comprised of cyclophosphamide
plus Flu/TBI
- Proposed additional clinical trial to evaluate Iomab-B plus
Flu/TBI compared to a single regimen comprised of cyclophosphamide
plus Flu/TBI which differs from the SIERRA trial that allowed
physician's choice of salvage therapy and heterogenous conditioning
regimens in the control arm
- The proposed additional clinical trial will not allow
crossover, which was allowed in SIERRA, and confounded the overall
survival analysis in the intent to treat (ITT) patient population
as nearly 60% of patients crossed over from the control arm
- Actinium intends to further discuss the specifics of the
additional clinical trial including the patient population, which
the FDA has suggested could include all adult AML patients
- Upon conclusion of its interactions with the FDA, Actinium will
seek a strategic partner for Iomab-B for the U.S.
Dr. Avinash Desai, Actinium's
Chief Medical Officer, said, "While this is not the outcome we
expected, we will work with the FDA to further discuss specifics of
the proposed randomized head-to-head clinical study to determine
its strategic feasibility. The 12 oral presentations of the SIERRA
results at prestigious bone marrow transplant, hematology and
nuclear medicine medical conferences in the U.S. and EU are an
attestation of the strong interest from the transplant community
for better conditioning regimens due to the high unmet need. We are
grateful to the patients, their families, as well as the study
investigators and their staff who participated in the SIERRA trial.
As a first of its kind study, SIERRA broadened the investigation of
Iomab-B as a targeted induction and conditioning agent from a
single center to twenty-four leading bone marrow transplant centers
in North America, demonstrating
its potential for the first time in a randomized, controlled study.
Through the conduct of SIERRA, Actinium also built strong
relationships with key thought leaders. This track record will
provide a solid foundation to work with a partner on a subsequent
Iomab-B trial, and we look forward to finalizing the path forward
for Iomab-B in the U.S. with the FDA."
Sandesh Seth, Actinium's Chairman
and CEO, said, "We are disappointed that the positive results from
the SIERRA trial are not deemed adequate by the FDA to support a
BLA filing despite meeting the primary endpoint with statistical
significance and producing positive efficacy and safety outcomes on
several measures. SIERRA represented a first of its kind
radiotherapeutic trial and demonstrated Actinium's ability to
execute seamlessly across manufacturing, supply chain, clinical
development, and operations. We intend to leverage these
capabilities as we continue to advance our highly differentiated
antibody radiation conjugate pipeline for cell & gene therapy
conditioning, hematology therapeutics and solid tumor candidates.
We are committed to establishing the best development path forward
for Iomab-B in the U.S. and finding a partner, while keeping
internal resources and strategic priorities in focus."
About Actinium Pharmaceuticals, Inc.
Actinium develops Antibody Radiation Conjugates ("ARCs") and
other targeted radiotherapies intended to meaningfully improve
outcomes for people who have failed existing oncology therapies.
Iomab-B is an induction and conditioning agent prior to bone marrow
transplant in patients with relapsed and refractory acute myeloid
leukemia ("r/r AML"), which Actinium plans to advance with a
potential strategic partner in the U.S. following completion of FDA
interactions. The company continues to advance its development for
product candidate Actimab-A, a therapeutic agent that has
demonstrated potential activity in r/r AML patients. In addition,
Actinium is engaged with the National Cancer Institute ("NCI")
under the Cooperative Research and Development Agreement ("CRADA")
for development of Actimab-A in AML and other myeloid malignancies.
Iomab-ACT, Actinium's next generation conditioning candidate, is
being developed with the goal of improving patient access and
outcomes for potentially curative cell and gene therapies. In
addition, the company's R&D efforts are primarily focused on
advancing several preclinical programs for solid tumor indications.
Actinium holds more than 235 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
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SOURCE Actinium Pharmaceuticals, Inc.