|[January 08, 2014]
Neumedicines' Study Shows HemaMax, Not Neupogen (G-CSF), Improves Survival Outcomes Following Lethal Irradiation
PASADENA, Calif. --(Business Wire)--
Neumedicines Inc., a privately held company developing therapies based
on interleukin-12 (IL-12) as a radiation medical countermeasure and as a
hematopoietic immunotherapeutic (HIT) for use in cancer patients, today
announced results from a blinded, randomized, placebo-controlled study
that demonstrate a significant increase in survival in non-human
primates treated with a single, low-dose, subcutaneous injection of
HemaMax™ (recombinant human interleukin-12) versus control (56% versus
36%; p<0.05) 60 days after exposure to lethal radiation.
In a comparator group, 18 consecutive days of treatment with Neupogen®
(filgrastim or granulocyte colony-stimulating factor [G-CSF]) did
not provide any survival benefit versus control (31% for Neupogen®
versus 36% for the control group). In a combination group, 18
consecutive days of G-CSF and a single dose of HemaMax™ showed a
survival benefit of 58%, which was not a statistically significant
improvement of the survival benefit compared with HemaMax™ alone (56%).
G-CSF is an FDA-approved drug for use in cancer patients to stimulate
the growth of neutrophils following chemotherapy. Although G-CSF is not
approved by FDA for the treatment of HSARS, according to the Centers for
Disease Control and Prevention (CDC) and the Radiation Injury Treatment
Network (RITN), G-CSF is the currently recommended emergency use
treatment option for victims of a radiation disaster.
The study, conducted by Neumedicines, was funded by the Biomedical
Advanced Research & Development Authority (BARDA) of the U.S. Department
of Health and Human Services (DHHS) as part of its ongoing support of
the development of HemaMax™ for the treatment of hematopoietic syndrome
of acute radiation sickness (HSARS). The study was conducted under good
laboratory practices (GLP).
Neumedicines is advancing the development of HemaMax™ toward a Biologics
License Application (BLA) submission under the FDA's Animal Rule (21 CFR
601.90-95) to treat HSARS that could result from a nuclear or
radiological weapon or nuclear accident. Currently, there is no
FDA-approved drug for HSARS mitigation. The present study provides
strong supportive evidence of the efficacy and safety of HemaMax™ for
the treatment of HSARS. Safety data from studies in humans and a
confirmatory efficacy study in non-human primates are planned in order
to provide sufficient data required to support a BLA for HemaMax™ for
the treatment of HSARS.
"This study reproduced the survival benefit results observed in our
previous efficacy studies and extends those findings by demonstrating a
significant survival advantage over a regimen of 18 consecutive days of
treatment with G-CSF," said Neumedicines President & CEO Lena A. Basile,
Ph.D., J.D. "These results represent a major step toward consideration
for pre-Emergency use Authorization (pre-EUA). Pre-EUA opens the door
for U.S government stockpiling of HemaMax™ for use in patients in the
event of exposure to lethal doses of radiation."
All treatments, HemaMax™, G-CSF, and control, were administered
subcutaneously starting 24-25 hours after total body irradiation. No
antibiotics, fluids or blood products were administered during the
study. The dose of HemaMax™ administered in this study is equivalent to
a human dose that has been established as safe and well-tolerated in
both a 32-patient first-in-human study and a 60-patient Phase 1b study
in healthy volunteers.
"These findings strongly support the further development of HemaMax™ as
a single-agent, single-dose, frontline defensive agent to counteract the
effects of HSARS, as well as for the hematopoietic support of cancer
patients undergoing radiation and chemotherapy," stated Dr. Basile.
"HemaMax™ is the only drug that has shown the ability to induce early
bone marrow regeneration followed by the hematopoietic recovery of all
blood cell lineages, which is necessary to support survival following
exposure to lethal radiation without antibiotics, fluids or blood
The Neumedicines study showed that HemaMax™ alone significantly
decreased frequency of severe neutropenia (<100 cells/µL, p<0.006) and
severe thrombocytopenia (<10,000 cells/µL, p<0.0001) compared to vehicle
or G-CSF. A combination of G-CSF and HemaMax™ augmented the rate and
extent of hematopoietic recovery in all lineages relative to that
achieved with HemaMax™ alone. Although the improvement in blood cell
counts did not translate to better survival than in the HemaMax™
monotherapy group, the data demonstrate that G-CSF can be safely
administered after HemaMax™, if deemed necessary.
Dr. Zoya Gluzman-Poltorak, Neumedicines Senior Nonclinical Director,
added, "Although the study results indicated that G-CSF alone had a
delayed positive effect on neutrophils in those non-human primates that
survived, it showed no effect on the nadir of neutrophil, platelet or
red blood cell counts and showed a negative effect on the nadir for
lymphocyte and reticulocyte counts. Consequently, without the supporting
multilineage bone marrow regeneration that we saw with HemaMax™, it is
not surprising in this study that G-CSF did not produce survival benefit
as a monotherapy. Concern about the usefulness of G-CSF as a radiation
medical countermeasure also has been raised due to potential negative
effect of G-CSF on radiation-induced lung injury and radiation-induced
These results differ from those of a recently conducted study that
demonstrated for the first time a benefit for G-CSF administered in the
post-irradiation setting, where G-CSF was administered along with an
intensive, trigger-based medical management regimen. "The
reproducibility of these results for G-CSF remains to be demonstrated,"
stated Vladimir Vainstein, MD MSc, of the Hebrew University Hadassah
Medical Center in Jerusalem and Clinical Advisor to Neumedicines.
"Moreover, these results were obtained in the context of highly
intensive, trigger-based multi-modal medical support. In a mass casualty
setting, the availability of analogous, intensive, hospital-based
medical management will be severely limited due to the availability of
hospital beds, and can be significantly delayed due to logistical
constraints of evacuating patients from contaminated areas to hospitals.
Further, a potential shortage of blood products and other supportive
care measures may render this approach nonviable."
Neumedicines is building a strong patent portfolio around the
ameliorating effects of HemaMax™ following injury to the bone marrow and
other tissues, such as its effects on wound healing. The company intends
to submit findings from the study for publication in a peer-reviewed
Nonclinical and clinical studies have been funded in whole or in part
with federal funds from the Biomedical Advanced Research and Development
Authority, Office of the Assistant Secretary for Preparedness and
Response, Office of the Secretary, Department of Health and Human
Services, under Contracts No. HHSO1002000800060C and No.
HemaMax™ is based on recombinant human interleukin-12 (IL-12). IL-12 is
a heterodimeric cytokine that has been shown to play an essential role
in regulating inflammatory responses, including innate resistance to
infection and an ability to stimulate the production of interferon-gamma
from natural killer cells, macrophages and T-cells. IL-12 also induces
resistance to many pathogens and to transplantable and chemically
About Neumedicines Inc.
Neumedicines Inc. is developing interleukin-12 (IL-12), which addresses
multiple indications including unmet clinical and societal needs in the
fields of oncology, hematology and immunology. The company's product
candidate, HemaMax™ (rHuIL-12), functions by targeting multiple pathways
of hematopoiesis and innate immunity. HemaMax™ is currently being
development as a biodefense radiation medical countermeasure and for
indications in oncology, initially as a hematopoietic immunotherapeutic
(HIT) in cancer patients receiving aggressive chemotherapy. Neumedicines
is committed to developing and maximizing the scientific, clinical and
commercial potential of its product pipeline. For more information,
please visit www.neumedicines.com
or follow the company on Twitter (News - Alert) @Neumedicines.
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