- EBMT oral presentation builds
awareness for Iomab-B and the SIERRA trial results with the
European transplant community that performs twice as many
transplants compared to the U.S.
- Iomab-B enabled unprecedented 100%
bone marrow transplant access and engraftment with 75% post-BMT CR
rate in patients with active, relapsed or refractory acute myeloid
leukemia who are considered unfit and transplant ineligible in
routine clinical practice
- Iomab-B met the SIERRA trial primary
endpoint of durable Complete Remission (dCR) with high statistical
significance (p<0.0001) and had a favorable safety profile
compared to the control arm
- 92% 1-year survival and 60% 2-year
survival in patients achieving dCR, median overall survival has not
been reached in these patients
NEW
YORK, April 27,
2023 /PRNewswire/ -- Actinium Pharmaceuticals, Inc.
(NYSE AMERICAN: ATNM) ("Actinium" or the "Company"), a leader in
the development of targeted radiotherapies, today announced that
the positive results from the pivotal Phase 3 SIERRA Trial of
Iomab-B were presented in an oral presentation at the European
Society for Blood and Marrow Transplantation (EBMT) 49th
Annual Meeting that was held in Paris,
France April 23 – 26, 2023. Europe represents a large market opportunity
with approximately twice as many transplants performed in
Europe compared to the United
States.The SIERRA trial is the first randomized Phase 3 trial to
take unfit, transplant ineligible patients with active relapsed or
refractory (r/r) acute myeloid leukemia (AML) age 55 and above to
bone marrow transplant (BMT), which was feasible due to Iomab-B's
novel targeted radiotherapy approach that allows patients to
receive a BMT without achieving a Complete Remission (CR).
As previously presented at the 2023 Tandem Meetings:
Transplantation & Cellular Therapy Meetings of the American
Society for Transplantation and Cellular Therapy (ASTCT) and the
Center for International Blood & Marrow Transplant Research
(CIBMTR) in February 2023, Iomab-B enabled unprecedented 100%
access to BMT in half the time, 29 days vs. 66.5 days, with 100% of
Iomab-B patients achieving engraftment, the first sign of BMT
success. Iomab-B met the study's primary endpoint of dCR of
6-months following initial complete remission after BMT with high
statistical significance (p-value of <0.0001) with only patients
receiving Iomab-B achieving dCR. The Iomab-B patients achieving dCR
had a 92% 1-year survival rate and a 60% 2-year survival rate,
which represents a potential cure, and median overall survival (OS)
has not been reached in the patients achieving dCR.
Sandesh Seth, Actinium's Chairman
and CEO, said, "Iomab-B and the SIERRA trial represent a paradigm
change for patients with r/r AML by making a BMT and its curative
potential a reality for the significant number of patients who
cannot achieve a CR or tolerate current induction and conditioning
therapies. We're thrilled the SIERRA results were showcased to the
European transplant community, as Europe represents a large commercial market
with twice as many BMTs performed in Europe compared to the US each year. With our
efforts fully underway to complete and submit our BLA for Iomab-B
with the FDA by the end of 2023, we are committed to bringing
Iomab-B to r/r AML patients globally and look forward to working
with Immedica, our European, Middle
East and North African (EUMENA) partner for their subsequent
marketing authorization application (MAA) with the European
Medicines Agency. With these positive results in hand, we're eager
to continue to build awareness for Iomab-B globally and to launch
an early access program for Iomab-B in the U.S. as well as launch
life cycle planning initiatives in the second half of this year to
leverage Iomab-B's potential across blood cancers."
Dr. Avinash Desai, Actinium's
Chief Medical Officer, added, "The efficacy and tolerability of
Iomab-B in these heavily pre-treated patients with active,
high-risk r/r AML enrolled in the SIERRA trial is unprecedented.
Despite 10 drug approvals for AML since 2017, approximately 30% of
patients never achieve a remission and over 50% develop relapsed or
refractory disease, which is associated with dismal survival
outcomes of 2-4 months. BMT remains the only potential curative
treatment option for r/r AML patients, but current clinical
practice precludes the overwhelming majority of r/r AML patients
from BMT due to the need to first achieve a remission and the use
of highly toxic, non-targeted chemotherapies for conditioning.
Based on the reaction to the SIERRA results from BMT physicians in
the U.S. and now Europe, if
approved, Iomab-B can be practice changing by enabling r/r AML
patients with active disease, one of the largest segments of AML,
to access BMT in days, via a single therapeutic infusion, without
having to first achieve a remission."
SIERRA Trial Results:
- 100% BMT access and engraftment with Iomab-B vs only 17% in the
control arm, where patients received current AML best practice
treatment comprised of 20 available agents including venetoclax
(Bcl-2 inhibitor), FLT3 inhibitors, IDH inhibitors, Mylotarg and
multiple cytotoxic chemotherapies
- Time to BMT was half in Iomab-B patients compared to control
arm patients – 29 days versus 66.5 days
- 75% of Iomab-B patients achieved Complete Remission (CR/CRp)
within 30 days following their BMT versus only 6.3% of patients on
the control arm
- 22% of Iomab-B treated patients achieved a dCR, the primary
endpoint of SIERRA versus 0% of control arm patients
(p<0.0001)
- Patients achieving dCR with Iomab-B had a 92% 1-year survival
rate and 60% 2-year survival rate; longer-term follow-up is ongoing
as median overall survival (OS) has not been reached in these
patients.
- Event-free survival, a secondary endpoint, was 26% versus 0.2%
in favor of Iomab-B with a Hazard Ratio of 0.22 (p<0.0001)
- Median OS was doubled in Iomab-B patients - 6.4 months versus
3.2 months in control arm patients who did not cross over – as was
1-year survival – 26.1% versus 13.1%
- Iomab-B had a favorable safety profile with more than 4-times
lower rates of sepsis (6.1% versus 28.6%) along with lower rates of
febrile neutropenia, mucositis and acute Graft Versus Host Disease
compared to control arm.
SIERRA Trial Iomab-B Patient Characteristics:
- Median blast count: 30%
- Prior lines of treatment: 3 (1-8)
- Median age: 64 (55-77)
- Intermediate and adverse cytogenetics and molecular risk:
>90%
- Majority of patients had primary induction failure or first
early relapse: 78%
EBMT Presentation Details:
Title: A Randomized Phase 3 Study of Allogeneic HCT with Iomab-B
Versus Conventional Care in Older Patients with Active,
Relapsed/Refractory AML: Pivotal SIERRA Trial Results
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. Event Free Survival was 26%,
compared to 0.02% in control arm with a Hazard Ratio of 0.22
(p<0.0001), in other words patients receiving Iomab-B had a 78%
lower probability of an event compared to control arm where event
is defined as not achieving a CR/CRp, crossing over to be rescued
by Iomab-B, not receiving a BMT, disease relapse or death. 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 very early crossover of 60%
patients from control arm to be rescued with Iomab-B. Crossover
patients had a 35.8% 1-year overall survival rate. Due to its
targeted nature, Iomab-B was well tolerated with more than four
times lower rates of sepsis compared to the control arm (6.1% vs.
28.6%) along with febrile neutropenia, mucositis and graft versus
host disease (GVHD). Actinium intends to submit a Biologics License
Application (BLA) seeking approval for Iomab-B in 2023 based on the
SIERRA data. Iomab-B has been granted Orphan Drug Designation from
the U.S. Food and Drug Administration (FDA) and has various 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 various
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 approximately over 30% of current 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
other 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 AB, a
full-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
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 Pharmaceuticals, Inc. is a clinical-stage
biopharmaceutical company developing targeted radiotherapies to
deliver cancer-killing radiation with cellular level precision to
treat patients with high unmet needs. Actinium's clinical pipeline
is led by targeted radiotherapies that are being applied to
targeted conditioning, which is intended to selectively deplete a
patient's disease or cancer cells and certain immune cells prior to
a bone marrow transplant (BMT), gene therapy or adoptive cell
therapy, such as CAR-T, to enable engraftment of these transplanted
cells with minimal toxicities. Our lead product candidate, Iomab-B
(I-131 apamistamab) has been studied in over four hundred patients,
including the pivotal Phase 3 Study of Iomab-B in Elderly Relapsed
or Refractory Acute Myeloid Leukemia (SIERRA) trial for BMT
conditioning. The SIERRA trial was positive with Iomab-B meeting
the primary endpoint of durable Complete Remission of 6-months with
high statistical significance (p<0.0001). Iomab-B enabled 100%
of patients to access a BMT and produced higher rates of post-BMT
CR. Iomab-B produced positive results for the secondary endpoints
of the SIERRA trial including reducing the probability of an event
by 78% resulting in an Event-Free Survival (EFS) Hazard Ratio of
0.22 (p<0.0001), doubled 1-year overall survival and median
overall survival. Iomab-ACT, low dose I-131 apamistamab, is being
studied as a targeted conditioning agent in a Phase 1 study with a
CD19 CAR T-cell Therapy with Memorial Sloan Kettering Cancer Center
with NIH funding. Actimab-A, our second most advanced product
candidate has been studied in approximately 150 patients with Acute
Myeloid Leukemia or AML, including in combination trials with the
chemotherapy regimen CLAG-M and with venetoclax, a targeted
therapy. Actimab-A or lintuzumab-Ac225 is an Actinium-225 based
antibody radiation conjugate targeting CD33, a validated target in
AML. Actinium has entered into a Cooperative Research and
Development Agreement (CRADA) with the National Cancer Institute
(NCI) to develop Actimab-A as a single agent or combination with
chemotherapy, targeted agents or immunotherapy in Phase 1, 2 or 3
trials. The NCI will fund clinical trial expenses under the CRADA
while Actinium will supply Actimab-A. The NCI is currently
accepting proposals for non-clinical and clinical studies with
Actimab-A. Actinium is a pioneer and leader in the field of
Actinium-225 alpha therapies with an industry leading technology
platform comprising over 190 patents and patent applications
including methods of producing the radioisotope AC-225. Our
technology and expertise have enabled collaborative research
partnerships with Astellas Pharma, Inc. for solid tumor
theranostics, with AVEO Oncology Inc. to create an Actinium-225
HER3 targeting radiotherapy for solid tumors, and with EpicentRx,
Inc. to create targeted radiotherapy combinations with their novel,
clinical stage small molecule CD47-SIRPα inhibitor. More
information is available on Actinium's website:
https://www.actiniumpharma.com/.
Forward-Looking Statements for Actinium Pharmaceuticals,
Inc.
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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