Funding will support development activities required for supplemental biological license application (sBLA) for Leukine to treat myelosuppressive effects and restore hematopoietic and immune function after HD exposure
LEXINGTON, MA – February 17, 2022 – Partner Therapeutics, Inc. (PTx) today announced a milestone-based Other Transaction Agreement (OTA) with the United States Department of Defense (DoD) to fund development and regulatory activities to support an sBLA of Leukine® (sargramostim, rhu-Granulocyte Macrophage Colony Stimulating Factor, “GM-CSF”) for the treatment of sulfur mustard gas (HD) exposure under the U.S. Food and Drug Administration’s (FDA) “Animal Rule” (21 CFR 314.600-650). The funding includes a base agreement of $5 million, with optional periods that may be exercised to support research and regulatory initiatives. Funding is provided through the DoD’s Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND). There are currently no medical countermeasures (MCMs) approved by the FDA to treat myelosuppressive effects of HD exposure.
“We are grateful to the DoD’s JPEO-CBRND for supporting advanced development of Leukine in HD exposure,” said John McManus, Chief Business Officer of Partner Therapeutics, Inc. “Data from Leukine’s use in approved indications and data generated to support Leukine’s approval for acute radiation syndrome support the hypothesis that administering Leukine after HD exposure could lead to accelerated recovery of immune function and improved outcomes. We look forward to working with the JPEO-CBRND and continuing to expand the utility of Leukine as an MCM in areas of interest to the United States Government.”
This collaboration represents PTx’s second partnership with the JPEO-CBRND to expand the utility of Leukine as an MCM beyond its current approved use to treat myelosuppressive effects of acute radiation exposure. The JPEO-CBRND previously awarded $39.5 million to support development of Leukine as a therapeutic to enhance immune response in high-risk non-hospitalized patients with COVID-19 and to improve oxygenation and lung function in hospitalized COVID-19 patients receiving oxygen support. Leukine achieved the primary endpoint (improvement in oxygenation) in the hospitalized patient study (iLeukPulm) and results from a 600-patient placebo-controlled study in high-risk non-hospitalized patients (SCOPE) are expected in the next quarter.
“Working with PTx will help advance our fight against HD exposure,” said Col. Ryan Eckmeier, the JPEO-CBRND’s Joint Project Manager for Chemical, Biological, Radiological, and Nuclear (CBRN) Medical. “Investing in repurposing the broad-spectrum immune modulator Leukine will support our core mission of protecting our nation’s warfighters from CBRN threats.”
Leukine is FDA-approved for the treatment of acute radiation syndrome (ARS) and is held by the U.S. Government for national preparedness. Leukine is not approved for treatment of sulfur mustard exposure.
About Sulfur Mustard Gas Exposure
Victims of HD exposure experience bone marrow suppression leading to myelosuppression and pancytopenia.1-5 HD acts at different sites in the body as a radio-mimetic with symptoms including headache, nausea, vomiting, anorexia, epigastric pain, leukopenia, thrombocytopenia, and anemia.4-11 Mortality in victims of HD exposure in World War I, World War II and the Iran-Iraq conflict were associated with lymphopenia, leukopenia and septicemia, pointing to the need for an HD MCM that can accelerate recovery of lymphocytes, other white blood cell lineages and platelets, restore immune homeostasis and barrier integrity, and effectively modulate and improve leukocyte function and antimicrobial immunity of the systemic immune system.4-14
LEUKINE® (sargramostim) is a yeast-derived recombinant human granulocyte-macrophage colony stimulating factor (rhuGM-CSF).
Leukine is indicated:
- To shorten time to neutrophil recovery and to reduce the incidence of severe and life-threatening infections and infections resulting in death following induction chemotherapy in adult patients 55 years and older with acute myeloid leukemia (AML).
- For the mobilization of hematopoietic progenitor cells into peripheral blood for collection by leukapheresis and autologous transplantation in adult patients.
- For the acceleration of myeloid reconstitution following autologous bone marrow or peripheral blood progenitor cell transplantation in adult and pediatric patients two years of age and older.
- For the acceleration of myeloid reconstitution following allogeneic bone marrow transplantation in adult and pediatric patients two years of age and older.
- For treatment of delayed neutrophil recovery or graft failure after autologous or allogeneic bone marrow transplantation in adult and pediatric patients two years of age and older.
- To increase survival in adult and pediatric patients from birth to 17 years of age acutely exposed to myelosuppressive doses of radiation (Hematopoietic Syndrome of Acute Radiation Syndrome [H-ARS]).
Important Safety Information for Leukine (sargramostim)
- LEUKINE is contraindicated in patients with known hypersensitivity to human granulocyte-macrophage colony stimulating factor such as sargramostim (GM-CSF), yeast-derived products, or any component of LEUKINE.
Warnings and Precautions
- Serious hypersensitivity reactions, including anaphylactic reactions, have been reported with LEUKINE. If any serious allergic or anaphylactic reaction occurs, immediately discontinue LEUKINE therapy and institute medical management. Permanently discontinue LEUKINE in patients with serious allergic reactions.
- LEUKINE can cause infusion-related reactions, including respiratory distress, hypoxia, flushing, hypotension, syncope and/or tachycardia. Observe closely during infusion, particularly in patients with preexisting lung disease, as dose adjustment or discontinuation may be required.
- Do not administer LEUKINE simultaneously with or within 24 hours preceding cytotoxic chemotherapy or radiotherapy or within 24 hours following chemotherapy.
- Edema, capillary leak syndrome, pleural and/or pericardial effusion have been reported in patients after LEUKINE administration. LEUKINE should be used with caution and monitored in patients with preexisting fluid retention, pulmonary infiltrates, or congestive heart failure.
- Supraventricular arrhythmia has been reported in uncontrolled studies during LEUKINE administration, particularly in patients with a previous history of cardiac arrhythmia. Use LEUKINE with caution in patients with preexisting cardiac disease.
- If absolute neutrophil count (ANC) is greater than 20,000 cells/mm3 or if white blood cell (WBC) counts are greater than 50,000/mm3, LEUKINE administration should be interrupted or the dose reduced by half. Twice weekly monitoring of CBC with differential should be performed.
- LEUKINE therapy should be discontinued if disease progression is detected during treatment.
- Treatment with LEUKINE may induce neutralizing anti-drug antibodies. Use LEUKINE for the shortest duration required.
- Liquid solutions containing benzyl alcohol (including LEUKINE Injection) or LEUKINE for Injection reconstituted with Bacteriostatic Water for Injection, USP (0.9 percent benzyl alcohol) should not be administered to neonates and low birth weight infants.
- Concomitant use of drugs that can potentiate the myeloproliferative effects of LEUKINE should be avoided.
Adverse events occurring in greater than 10 percent of patients receiving LEUKINE in controlled clinical trials and reported in a higher frequency than placebo are:
- In Autologous bone marrow transplantation (BMT) patients–asthenia, malaise, diarrhea, rash, peripheral edema, urinary tract disorder
- In Allogeneic BMT patients–abdominal pain, chills, chest pain, diarrhea, nausea, vomiting, hematemesis, dysphagia, gastrointestinal (GI) hemorrhage, pruritus, bone pain, arthralgia, eye hemorrhage, hypertension, tachycardia, bilirubinemia, hyperglycemia, increased creatinine, hypomagnesemia, edema, pharyngitis, epistaxis, dyspnea, insomnia, anxiety, high glucose, low albumin
- In AML patients–fever, weight loss, nausea, vomiting, anorexia, skin reactions, metabolic laboratory abnormalities, edema
ABOUT PARTNER THERAPEUTICS
PTx, an integrated biotechnology company, focuses on development and commercialization of late-stage therapeutics to improve health outcomes in treatment of cancer and other serious diseases. The company believes in delivering products and supporting medical teams with the purpose of achieving superior outcomes for patients and their families. Visit careers.partnertx.com
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- Sulfur Mustard (Blister Agent) Fact Sheet, Johns Hopkins Center for Health Security, 2020.
- EMEA/CPMP Guidance Document on the Use of Medicinal Products for the Treatment of Patients Exposed to Terrorist Attacks with Chemical Agents, EMEA, Pre-authorisation Evaluation of Medicines for Human Use, London, April 2003.
- Willems, JL, Clinical management of mustard gas casualties, Ann Med Milit Belg 1989; 3: S1-61.
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- Anderson DR, Sulfur Mustard-Induced Neutropenia: Treatment with G-CSF; Military Medicine, 171, 5:448, 2006.
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- Sidell FR, Hurst CG, Clinical considerations in mustard poisoning, Chemical Warfare Agents; 51-66, Academic Press, 1992.
- Sezigan S, et. al., Myelosuppression and acute hematological complications of sulfur mustard exposure in victims of chemical terrorism, Toxicology Letters 318 (2020) 92-98.
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- Leukine® Package Insert, PartnerTherapeutics, Inc. (Lexington, MA, 2018)