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TMCNet:  Neumedicines' Study Shows HemaMax, Not Neupogen (G-CSF), Improves Survival Outcomes Following Lethal Irradiation

[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 products."

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 tumorigenesis."

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 medical journal.

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. HHSO100201100037C.

About HemaMax™

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 induced tumors.

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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