Partner Therapeutics' Leukine® (sargramostim) Receives Approval in Japan to Treat Autoimmune Pulmonary Alveolar Proteinosis (aPAP)
Treatment will be Marketed by Nobelpharma Co. Ltd. Under the Trade Name Sargmalin(®)
PMDA Approval of Sargmalin is the first regulatory approval of an inhaled recombinant GM-CSF product for aPAP
LEXINGTON, Mass., April 3, 2024 /PRNewswire/ -- Partner Therapeutics, Inc. (PTx) announced that its partner Nobelpharma received approval from the Japanese Pharmaceuticals and Medical Device Agency (PMDA) for the inhaled use of Leukine (sargramostim), branded in Japan as Sargmalin, to treat aPAP. PTx licensed rights for certain indications in Japan to Nobelpharma in 2022. Leukine is a glycosylated recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) produced by recombinant DNA technology in yeast. Leukine is not approved outside Japan for aPAP or as an inhalation therapy. Partner Therapeutics will manufacture Sargmalin for Nobelpharma at its manufacturing facility in Lynnwood, WA.
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)
REFERENCES
1. Tazawa R, Ueda T, Abe M, et al. Inhaled GM-CSF for Pulmonary Alveolar
Proteinosis. N Engl J Med. 2019;381(10):923-32.
2. Seymour JF, Presneill JJ. Pulmonary alveolar proteinosis. Progress in the
first 44 years. Am J Respir Crit Care Med. 2002;166(2);215-35.
3. 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.
4. McCarthy C, Carey BC and Trapnell BC. Autoimmune pulmonary alveolar
proteinosis. Am J Respir Crit Care Med 2022;205(9):1016-1035.
ABOUT LEUKINE
LEUKINE (sargramostim) is a glycosylated recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) produced by recombinant DNA technology in yeast. The product is commercially available in the United States and accessible through a named patient program operated by Tanner Pharma Group outside of the United States.
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 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.
-- 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)
Contraindications
-- Do not administer LEUKINE to patients with a history of serious allergic
reaction, including anaphylaxis, to human granulocyte-macrophage
colony-stimulating factor, sargramostim, yeast-derived products, or any
other component of LEUKINE.
Warnings and Precautions
-- Serious hypersensitivity reactions, including anaphylactic reactions,
have been reported with LEUKINE. If a serious allergic or anaphylactic
reaction occurs, immediately discontinue LEUKINE therapy, and institute
medical management. Discontinue LEUKINE permanently for patients with
serious allergic reactions.
-- LEUKINE can cause infusion-related reactions that may be characterized
by respiratory distress, hypoxia, flushing, hypotension, syncope, and/or
tachycardia. Observe closely during infusion, particularly in patients
with preexisting lung disease; dose adjustment or discontinuation may be
needed.
-- LEUKINE should not be administered simultaneously with or within 24
hours preceding cytotoxic chemotherapy or radiotherapy or within 24
hours following chemotherapy.
-- Edema, capillary leak syndrome, and pleural or pericardial effusions
have been reported in patients after LEUKINE administration. LEUKINE
should be used with caution in patients with preexisting fluid
retention, pulmonary infiltrates, or congestive heart failure. Such
patients should be monitored.
-- Supraventricular arrhythmia has been reported in uncontrolled studies
during LEUKINE administration, particularly in patients with a history
of cardiac arrhythmia. Use LEUKINE with caution in patients with
preexisting cardiac disease.
-- 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.
-- Discontinue LEUKINE therapy if tumor progression, particularly in
myeloid malignancies, is detected during LEUKINE treatment.
-- 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.
Drug Interactions
-- Avoid the concomitant use of LEUKINE and products that induce
myeloproliferation. Monitor for clinical and laboratory signs of excess
myeloproliferative effects.
Adverse Reactions
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 autologous bone marrow transplantation (BMT)-asthenia,
malaise, diarrhea, rash, peripheral edema, urinary tract disorder
-- 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
-- In patients with AML-fever, weight loss, nausea, vomiting, anorexia,
skin reactions, metabolic laboratory abnormalities, edema
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.
View original content to download multimedia:https://www.prnewswire.com/news-releases/partner-therapeutics-leukine-sargramostim-receives-approval-in-japan-to-treat-autoimmune-pulmonary-alveolar-proteinosis-apap-302107763.html
SOURCE Partner Therapeutics, Inc.
