- Relapsed or refractory AML patients with TP53 mutation known to
have dismal outcomes due to limited effective treatment options
- Median Overall Survival of 5.49 months observed in patients
with a TP53 mutation receiving an Iomab-B led allogeneic bone
marrow transplant compared to 1.66 months in patients that did not
receive Iomab-B (hazard ratio=0.23, p=0.0002)
- Eighth oral presentation of Iomab-B data since announcement of
positive Phase 3 SIERRA Results
NEW
YORK, Dec. 11, 2023 /PRNewswire/ -- Actinium
Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the
Company), a leader in the development of targeted radiotherapies,
today announced that results from the Phase 3 SIERRA trial of
Iomab-B were presented in an oral presentation at the
65th Annual American Society of Hematology Meeting &
Exposition (ASH). The oral presentation highlighted significantly
improved survival in patients with a TP53 mutation receiving
Iomab-B.
Iomab-B is a targeted radiotherapeutic comprised of an anti-CD45
monoclonal antibody with the Iodine-131 radioisotope payload. The
Phase 3 SIERRA trial enrolled 153 patients with active relapsed or
refractory acute myeloid leukemia (AML) and compared outcomes of
patients receiving Iomab-B and a bone marrow transplant (BMT) to
those of patients receiving physician's choice of care in the
control arm, which was intended to reflect current best practices.
Patients not achieving a Complete Remission (CR) in the control arm
who were unable to proceed to a BMT were offered to crossover to
receive an Iomab-B led BMT.
Iomab-B achieved the primary endpoint in the SIERRA trial of
durable Complete Remission (dCR) of at least 6 months with high
statistical significance (p<0.0001), with 22% of patients
randomized to the Iomab-B arm achieving dCR and 0% of patients in
the control arm achieving dCR, irrespective of TP53 mutational
status. In addition, Iomab-B significantly improved event-free
survival, a secondary endpoint, with a hazard ratio of 0.22 and
median overall survival (mOS) was doubled.
Data highlighted in the ASH oral presentation, which can be
accessed on the investor relations page of Actinium's website,
included:
Overall Survival in Patients with a TP53 Mutation:
|
Iomab-B &
Crossover
|
Control
Arm
|
Median
OS
|
5.49 months
|
1.66 months
|
Number of
Patients
|
27
|
10
|
Hazard
Ratio
|
0.23
|
p-value
|
0.0002
|
|
Median OS was 6.37 months in TP53 negative patients receiving
Iomab-B and 5.72 months for TP53 positive patients demonstrating
Iomab-B's ability to overcome TP53 gene mutations.
Response rates by TP53 Mutation Status:
|
Iomab-B &
Crossover
|
Control
Arm
|
TP53
Positive
|
N=27
|
N=10
|
CR
|
55.56%
(15/27)
|
0 %
|
dCR
|
14.81%
(4/27)
|
0 %
|
TP53
Wildtype
|
N=93
|
N=23
|
CR
|
58.06%
(54/93)
|
17.39%
(4/23)
|
dCR
|
16.13%
(15/93)
|
0 %
|
|
Dr. Hannah Choe, Assistant
Professor of Medicine at Ohio State
University and SIERRA trial investigator, commented,
"Patients with a TP53 mutation have notoriously
poor outcomes due to resistance to anti-leukemic therapies and
are rarely offered access to potentially curative transplantation.
Iomab-B can grant patients increased access to transplant and
induces high complete remission rates despite active,
relapsed/refractory disease and even in those with a TP53 mutation.
This speaks to the novelty and safety of a CD45-directed
radiotherapy. More importantly, we see that these response rates
translated into improved overall survival, overcoming the increased
risk associated with TP53 mutation while no other viable treatment
options exist. We are excited to present these results that further
support the use and safety of Iomab for disease control."
Overall, twenty-four percent (37/153) of patients enrolled on
SIERRA had a TP53 mutation. In total, 27 patients with a TP53
mutation received Iomab-B and accessed BMT on the SIERRA trial
either after initial randomization or following crossover after not
being able to access a BMT on the control arm. Only 1 patient with
a TP53 mutation was able to access a BMT on the control arm via
conventional care.
Dr. Avinash Desai, Actinium's
Chief Medical Officer, added, "The SIERRA trial data support that
regardless of advanced age, prior therapy, or high-risk
cytogenetics including a TP53 mutation, Iomab-B provides
unprecedented access to a potentially curative BMT. The results
also show that on a population basis and across subgroups, an
Iomab-B led BMT may result in improved survival. We are incredibly
excited for the potential of Iomab-B and what it represents for
patients with relapsed or refractory AML. The international
enthusiasm for the SIERRA data amongst key medical and scientific
communities is evidenced by the eight oral presentations at some of
the most prestigious medical conferences held this year including
TCT, EBMT, ONS, EHA, SNMMI, EANM, SOHO and now ASH is highly
motivating, and we are committed to bringing Iomab-B to transplant
physicians and their patients globally."
About Iomab-B and the Pivotal Phase 3 SIERRA Trial
Iomab-B is a first-in-class targeted radiotherapy intended to
improve patient access to potentially curative BMT by
simultaneously and rapidly depleting blood cancer, immune and bone
marrow stem cells that uniquely express CD45. Multiple studies have
demonstrated increased survival in patients receiving BMT, however,
an overwhelming majority of patients with blood cancers do not
receive BMT as current approaches do not produce a remission, which
is needed to advance to BMT, or are too toxic. Studied in over 400
patients, prior studies with Iomab-B have demonstrated nearly
universal access to BMT, increased survival and tolerability in
multiple clinical trials including the recently completed pivotal
Phase 3 SIERRA trial in patients with active (leukemic blasts
>5%), relapsed or refractory acute myeloid leukemia (r/r AML)
age 55 and above.
Iomab-B met the primary endpoint of durable Complete Remission
(dCR) of 6 months after initial remission post-BMT in the pivotal
Phase 3 SIERRA trial with high statistical significance
(p<0.0001). Iomab-B produced a 75% post-BMT CR rate (44/59
patients), which is 12-times greater than the post-BMT rate of 6.3%
(4/64 patients) in the control arm. Patients receiving Iomab-B had
a 78% lower probability of an event, defined as not achieving a
CR/CRp, crossover, not receiving a BMT, relapse or death, with a
Hazard Ratio of 0.22 (p<0.0001). Iomab-B doubled 1-year overall
survival with 26.1% compared to 13.1% in the control arm for
patients who did not crossover as well as median overall survival
with 6.4 months vs 3.2 months. Overall survival statistics are
confounded by the crossover arm. Crossover patients had a 35.8%
1-year overall survival rate. Due to its targeted nature, Iomab-B
was well tolerated with four times lower rates of sepsis compared
to the control arm (6.1% vs. 28.6%) and lower rates of BMT
associated adverse events including febrile neutropenia, mucositis
and graft versus host disease (GVHD). Actinium intends to submit a
Biologics License Application (BLA) seeking approval for Iomab-B in
2024 to address patients age 55+ with r/r AML who cannot access BMT
with currently available therapies. Iomab-B has been granted Orphan
Drug Designation from the U.S. Food and Drug Administration (FDA)
and has patent protection into 2037.
The pivotal Phase 3 SIERRA (Study of Iomab-B in Elderly relapsed
or refractory AML) is a 153-patient, randomized, multi-center
clinical trial, studying Iomab-B compared to the control arm of
physician's choice of salvage therapy. Control arm options included
chemotherapies like cytarabine and daunorubicin and targeted agents
such as a Bcl-2 inhibitor (Venetoclax), FLT3 inhibitors and IDH 1/2
inhibitors. The SIERRA control arm reflects real-world treatment of
r/r AML patients with over 20 agents used alone or in combination
as no standard of care exists for this patient population. The
SIERRA trial enrolled patients at 24 leading transplant centers in
the United States and Canada that perform over 30% of AML BMTs.
Developed at the Fred Hutchinson Cancer Research Center, a
pioneer in the field of BMT, Iomab-B is supported by data in six
disease indications including leukemias, lymphomas and multiple
myeloma, which afflict over 100,000 patients annually. Actinium
intends to pursue additional indications for Iomab-B beyond AML.
Actinium also intends to pursue international regulatory approvals
independently and through partnerships. In April 2022, Actinium licensed the European,
Middle East and North African
commercial rights for Iomab-B to Immedica Pharma AB, a
fully-fledged independent pharmaceutical company headquartered in
Sweden. In exchange, Actinium
received an upfront payment of $35 million
USD with the potential for an additional $417 million USD in regulatory and sales
milestones and mid-twenty percent royalties. Europe represents a commercial opportunity
approximately double the size of the
United States by number of patients with AML receiving BMT.
Iomab-B has been granted Orphan Drug Designation by the European
Medicines Agency (EMA) and has received positive Scientific Advice
from the Committee for Medicinal Products for Human Use (CHMP) of
the EMA indicating that the Phase 3 SIERRA trial design, primary
endpoint and planned statistical analysis are acceptable as the
basis for a Marketing Authorization Application.
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), an
induction and conditioning agent prior to bone marrow transplant,
and Actimab-A (National Cancer Institute CRADA pivotal development
path), a therapeutic, 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's technology
platform is the basis for collaborations with Astellas Pharma for
solid tumors, AVEO Oncology/LG Chem Life Sciences for HER3 solid
tumors, and several internal programs in solid tumors. Actinium
holds more than 220 patents and patent applications.
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
Sources: Granowicz EM, Jonas BA.
Targeting TP53-Mutated Acute Myeloid Leukemia: Research
and Clinical Developments. Onco Targets Ther. 2022 Apr
21;15:423-436. doi: 10.2147/OTT.S265637. PMID: 35479302; PMCID:
PMC9037178.
View original content to download
multimedia:https://www.prnewswire.com/news-releases/actinium-announces-iomab-b-produces-high-response-rates-and-significant-improvement-in-overall-survival-in-relapsed-refractory-aml-patients-with-active-disease-overcoming-tp53-mutation-302011016.html
SOURCE Actinium Pharmaceuticals, Inc.