PMDA Approval of Sargmalin is the first regulatory approval of an inhaled recombinant GM-CSF product for aPAP
The Sargmalin approval is based on data from the PAGE trial, a phase 2 multicenter, randomized, double-blind, placebo-controlled study to evaluate Leukine in 64 patients with mild to moderate aPAP led by Sponsor-Investigator Koh Nakata MD, PhD, Project Professor, Division of Pioneering Advanced Therapeutics, Center for Medical Innovation of Niigata University Medical Dental Hospital. Patients were randomly assigned 1:1 to receive either 125 micrograms of Leukine or placebo twice per day for seven days and then off for seven days for twelve two–week cycles. There was a significant improvement (p=0.02) in the primary endpoint of improvement in alveolar–arterial oxygen gradient (A-aDO2) between baseline and week 25. Greater improvements in serum biomarker secondary endpoints KL-6, CEA, and monocyte chemoattractant protein-1 (MCP-1) were observed with Leukine.1 "We are grateful to Nobelpharma for their partnership as well as their deep commitment to making this treatment available to aPAP patients in Japan," said Robert Mulroy, CEO of Partner Therapeutics. "It has been a pleasure working with their team and we look forward to ensuring availability of Sargmalin. We also deeply appreciate the commitment of the many patients and doctors who participated in the investigator-initiated clinical trial led by Dr. Nakata of Niigata University." Investigation of inhaled sargramostim, a recombinant human GM-CSF, in aPAP is based on knowledge that the disease is a progressive lung disorder driven by blockage of GM-CSF signaling due to the production of GM-CSF autoantibodies.1,2 The deficiency of GM-CSF in aPAP patients inhibits their ability to differentiate monocytes into alveolar macrophages, which causes aPAP patients to accumulate surfactant in their lungs. This dysfunction leads to low oxygen levels, difficulty breathing, innate immune deficiency, and, in some cases, serious infection, pulmonary fibrosis, respiratory failure, and death.2 GM-CSF improves lung function by directly acting on alveolar macrophages to promote their maturation and the breakdown of pulmonary surfactant by mature macrophages.3 To date, the standard treatment for aPAP has been Whole Lung Lavage (WLL), a lengthy and invasive procedure where saline is used to wash the lungs of excess surfactant. WLL requires hospitalization, general anesthesia, and mechanical ventilation. While effective in providing short term symptomatic relief, WLL can also have serious complications and does not treat alveolar macrophage dysfunction, the underlying cause of aPAP.4 Campo I, Carey BC, Paracchini E, Kadija Z, De Silvestri A, Rodi G, et al. Inhaled recombinant GM-CSF reduces the need for whole lung lavage and improves gas exchange in autoimmune pulmonary alveolar proteinosis patients. Eur Respir J 2024;63(1):2301233. 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 2 years of age and older.
For the acceleration of myeloid reconstitution following allogeneic bone marrow transplantation in adult and pediatric patients 2 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 2 years of age and older. LEUKINE should not be administered simultaneously with or within 24 hours preceding cytotoxic chemotherapy or radiotherapy or within 24 hours following chemotherapy. If absolute neutrophil count (ANC) > 20,000 cells/mm3 or if white blood cell (WBC) counts > 50,000/mm3, LEUKINE administration should be interrupted, or the dose reduced by half. Monitor complete blood counts (CBC) with differential twice per week. Treatment with LEUKINE may induce neutralizing anti-drug antibodies. Use LEUKINE for the shortest duration needed. Avoid administration of solutions containing benzyl alcohol (including LEUKINE for injection reconstituted with Bacteriostatic Water for Injection, USP [0.9 % benzyl alcohol]) to neonates and low birth weight infants. Avoid the concomitant use of LEUKINE and products that induce myeloproliferation. Monitor for clinical and laboratory signs of excess myeloproliferative effects. Adverse events occurring in >10% of patients receiving LEUKINE in controlled clinical trials and reported at a higher frequency than in placebo patients are: In recipients of allogeneic BMT–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, low albumin ABOUT PARTNER THERAPEUTICS
Partner Therapeutics, Inc. (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 www.partnertx.com