Partner Therapeutics (PTx) Announces US FDA Approval of Leukine® (sargramostim) for the Treatment of Acute Radiation Syndrome
LEXINGTON, Mass., June 6, 2018 /PRNewswire/
Commercial-stage cancer biotech company, Partner Therapeutics, Inc. (PTx), announced the recent FDA approval of Leukine for the treatment of adult and pediatric patients acutely exposed to myelosuppressive doses of radiation (Hematopoietic Syndrome of Acute Radiation Syndrome, or H-ARS). Leukine is the first drug for H-ARS to demonstrate an improvement in survival when initiated 48 hours after radiation exposure.
Acute Radiation Syndrome (ARS) (sometimes known as radiation toxicity or radiation sickness) is an acute illness caused by irradiation of the body by a high dose of penetrating radiation. H-ARS occurs when the radiation exposure results in the destruction of the stem cells resident in the bone marrow that generate and maintain the body's immune system increasing the risk of infection, bleeding, and death. Leukine has the potential to improve survival in patients with H-ARS by facilitating recovery of blood cells that are important in helping the body's immune system fight infection.
Efficacy studies of Leukine could not be conducted in humans with acute radiation syndrome for ethical and feasibility reasons and approval of this use was based on government-sponsored efficacy studies conducted in animals. Leukine (7 mcg/kg/day) or placebo was initiated 48 hours after exposure to myelosuppressive doses of radiation expected to be fatal to 50-60% of in non-human primates at day 60, without requiring supportive whole blood transfusions or individualized antibiotics (36 animals per group). Leukine improved survival by 85% (78% vs 42%; p=0.0018) at day 60. In addition, in an exploratory cohort that received higher radiation exposures, myelosuppressive doses to be fatal in 70-80% of non-human primates at day 60, Leukine was also shown to improve survival: 61% survival (11/18) in the Leukine group compared to 17% survival (3/18) in the control group.1 Clinical studies of Leukine in patients undergoing autologous or allogeneic bone marrow transplantation which showed improvements in recovery of white blood cells, reduced incidence of severe and life-threatening infections, and improved survival were included as supportive data for this indication. In clinical studies of Leukine, the most commonly reported side effects with Leukine administration are fever, nausea, diarrhea, and vomiting. Hypersensitivity reactions and infusion-related reactions have been reported with Leukine injection. Patients, particularly those with pre-existing lung disease, should be closely observed for such events.
Leukine is a yeast-derived recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF). Leukine was initially approved in the United States in 1991 and has five hematology oncologic indications. The development of the H-ARS indication was funded completely with Federal funds from the Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority, under Contract No. HHSO100201300005I. Leukine received orphan designation for H-ARS in the U.S. in November 2016 and in April 2018was granted 7 years exclusivity period for this indication. A supplemental biologics licensing application (sBLA) was filed with FDA in September 2017 requesting approval of Leukine for treatment of H-ARS. In December, the application was granted Priority Review.
"In this study Leukine not only showed improved survival despite initiating therapy two days after the radiation exposure but also demonstrated these beneficial effects on survival at both standard and higher doses of radiation" said Debasish Roychowdhury, PTx Chief Medical Officer. "This latest approval in H-ARS is the beginning of a new era for Leukine with important ongoing studies in immunotherapy of cancers2 and other chronic debilitating disorders."
"Sometimes existing drugs are overlooked given the focus on developing new drugs. This creates the potential for missed opportunities. We are taking a different approach," said Colleen Mockbee, PTx Chief Development Officer. "Since the initial approval of Leukine, our knowledge of the immune system, as well as a deeper understanding of GM-CSF as a therapeutic agent has led to new development opportunities including autoimmune pulmonary alveolar proteinosis, Alzheimer's disease, and combinations with immune-oncology agents in the treatment of cancer. The approval of Leukine in H-ARS is just the beginning. We believe Leukine has the potential to positively impact the lives of many more patients."
The Company also announced today that FDA has issued a biologic license to PTx which completes the regulatory process for the transfer of Leukine to PTx.
See Full Prescribing Information for Leukine:
See FDA's Announcement Here:
About Partner Therapeutics, Inc.:
PTx is an integrated commercial-stage biotech company focused on the development and commercialization of therapeutics that improve health and economic outcomes in the treatment of cancer. PTx's development focus spans the entire range of cancer therapy from primary treatments to supportive care. The company believes in delivering great products in support of medical teams with the purpose of creating the best possible outcomes for patients and their families.
On February 1st, 2018, PTx announced it acquired the global rights to develop, manufacture, and commercialize Leukine from Sanofi.
Leukine® (sargramostim) is indicated for the following uses: (i) following induction chemotherapy in older adult patients with acute myelogenous leukemia (AML) to shorten time to neutrophil recovery; (ii) for mobilization and following transplantation of autologous peripheral blood progenitor cells; (iii) for myeloid reconstitution after autologous or allogeneic bone marrow transplantation (BMT); (iv) for use in bone marrow transplantation failure or engraftment delay; (v) for use following exposure to myelosuppressive doses of radiation.
Important Safety Information for Leukine (sargramostim)
Leukine is contraindicated in patients with known hypersensitivity to GM-CSF, yeast-derived products, or any component of Leukine.
Serious allergic or anaphylactic reactions have been reported with Leukine. If any serious allergic or anaphylactic reactions occur, Leukine therapy should be immediately discontinued and appropriate therapy initiated.
Liquid solutions containing benzyl alcohol (including Leukine Injection) or Leukine for Injection reconstituted with Bacteriostatic Water for Injection, USP (0.9% benzyl alcohol) should not be administered to neonates.
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, and occasional transient supraventricular arrhythmia have been reported in patients after Leukine administration. Leukine should be used with caution and monitored in patients with preexisting fluid retention, pulmonary infiltrates, congestive heart failure, or preexisting cardiac disease. Body weight and hydration status should be carefully monitored during Leukine administration.
Leukine can cause infusion-related reactions. Observe closely during infusion for symptoms, particularly in patients with preexisting lung disease.
Adverse events occurring in >10% of patients receiving Leukine in controlled clinical trials and reported in a higher frequency than placebo were: in AML patients – (fever, skin reactions, metabolic laboratory abnormalities, nausea, vomiting, weight-loss, edema, anorexia); in Autologous BMT patients – (asthenia, malaise, diarrhea, rash, peripheral edema, urinary tract disorder); and in Allogeneic BMT patients – (abdominal pain, chills, chest pain, diarrhea, nausea, vomiting, hematemesis, dysphagia, GI hemorrhage, pruritus, bone pain, arthralgia, eye hemorrhage, hypertension, tachycardia, bilirubinemia, hyperglycemia, increased creatinine, hypomagnesemia, edema, pharyngitis, epistaxis, dyspnea, insomnia, anxiety, high glucose, and low albumin).
If ANC > 20,000 cells/mm3 or if WBC counts > 50,000/mm3, Leukine administration should be interrupted or the dose reduced by half. Twice weekly monitoring of CBC with differential should be performed.
Treatment with Leukine may induce neutralizing anti-drug antibodies. Use Leukine for the shortest duration required.
Leukine therapy should be discontinued if disease progression is detected during treatment.
Concomitant use of drugs that can potentiate the myeloproliferative effects of Leukine, such as lithium and corticosteroids, should be avoided.
Clayton NP, et al. Sargramostim Accelerates Leukocyte Recovery and Improves Mortality Rate at Day 60 in a Non-Human Primate Model of Hematopoietic Acute Radiation Syndrome When Administered 48 h after Total Body Irradiation. Blood 2016: 128:2512a
National Cancer Institute. Nivolumab and ipilimumab with or without sargramostim in treating patients with stage III-IV melanoma that cannot be removed by surgery. Available at: https://clinicaltrials.gov/ct2/show/NCT02339571. NLM identifier: NCT02339571. Accessed March 22, 2018.
SOURCE Partner Therapeutics, Inc.