Exploratory Results Suggest the Potential Role of LEUKINE® as a Host-Directed Immunomodulator

Results of a prospective, randomized, placebo-controlled study of inhaled Leukine® in non-hospitalized patients at risk for severe COVID-19

LEXINGTON, Mass., Dec. 20, 2023 /PRNewswire/ -- Partner Therapeutics, Inc. (PTx) announced today that Open Forum Infectious Diseases recently published the results from the SCOPE study (doi.org/10.1093/ofid/ofad500.351).¹ These data were also presented at IDWeek 2023. The study was a prospective, multicenter study of 600 non-hospitalized COVID-19 patients randomized to receive either inhaled Leukine® (sargramostim; yeast-derived, glycosylated recombinant human granulocyte-macrophage colony-stimulating factor [rhu GM-CSF]) or placebo. SCOPE included patients diagnosed with symptomatic mild/moderate COVID-19 who were at high risk for progression to severe disease. Of the 600 patients, 93 were vaccinated. Inhaled sargramostim, administered daily for five days, was well tolerated, no cytokine changes were observed, and adverse events were generally similar across both arms. The primary study endpoint was to determine if inhaled sargramostim could prevent progression to more severe disease as determined by any emergency room visit, hospitalization, or death by day 28. No difference was found in the primary endpoint between treatment arms. However, the sargramostim arm had a greater reduction in overall symptom score (a secondary endpoint) than the placebo arm. Results of prior studies of sargramostim in patients hospitalized with COVID-19^2,3 showed inhaled sargramostim plus standard of care led to greater improvement in P(A–a)O₂, a measure of oxygenation, compared to standard of care alone.

Exploratory analyses of a biomarker cohort (n=101, containing both vaccinated and unvaccinated patients) revealed potential immunomodulatory effects of sargramostim. Humoral and cellular immune signatures adjust to a multiplying SARS-CoV-2 viral load during the progression from mild to severe COVID-19.^4,5 SCOPE investigators observed that treatment with inhaled sargramostim enhanced SARS-CoV-2 viral load clearance, modulated the humoral kinetics and magnitude against SAS-CoV-2 antigens, and suggested enhanced IgG4 expression and FcGR2B binding.² The effect of sargramostim on humoral immune response was more pronounced in patients who have received a COVID-19 vaccination. The translational data from this study show modulation of humoral immunity with sargramostim treatment.

Ila Joshi, Ph.D., Director of Biology, Pre-Clinical and Translational Research and Development at PTx observed, "The exploratory results from the biomarker cohort provide evidence of the potential for sargramostim to act as a virus-agnostic, host-directed immunomodulator. The combined effect of sargramostim and a COVID-19 vaccination observed on the humoral response, humoral kinetics, and viral load highlight a synergistic immune response against virus-specific antigens."

This effort was funded by the Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND) under project agreement MCDC2006-012. Included references to commercial products do not constitute an endorsement by the U.S. Defense Department or the JPEO-CBRND.

Leukine® is not approved to treat COVID-19.

ABOUT IDWEEK

IDWeek is the joint annual meeting of the Infectious Diseases Society of America, Society for Healthcare Epidemiology of America, the HIV Medicine Association, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists. IDWeek 2023 was held October 11-15, 2023, in Boston.

ABOUT Leukine®

Leukine® (sargramostim) is a glycosylated recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) produced by recombinant DNA technology in yeast.

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.
• 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).

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 > 20,000 cells/mm³ or if white blood cell counts > 50,000/mm³, Leukine® administration should be interrupted, or the dose reduced by half. Monitor complete blood counts 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–asthenia, malaise, diarrhea, rash, peripheral edema, urinary tract disorder.
• In recipients of allogeneic blood and marrow transplant–abdominal pain, chills, chest pain, diarrhea, nausea, vomiting, hematemesis, dysphagia, gastrointestinal 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 acute myeloid leukemia–fever, weight loss, nausea, vomiting, anorexia, skin reactions, metabolic laboratory abnormalities, edema.

ABOUT PARTNER THERAPEUTICS

Partner Therapeutics, Inc., 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.

ABOUT THE JPEO-CBRND

The Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND) mission is to provide an integrated layered chemical, biological, radiological, and nuclear defense capabilities to the Joint Force across combined Joint All-Domain Operations. JPEO-CBRND's goal is to enable the Joint Force to fight and win unencumbered by a CBRN environment. To learn more about JPEO-CBRND, visit: https://www.jpeocbrnd.osd.mil/, or follow JPEO-CBRND on social media @JPEOCBRND.

References:

¹ Joshi I, Garner F, Roychowdhury DF, et al. Inhaled Sargramostim (rhu GM-CSF) Leads to Enhanced SARS-CoV-2 Virus-Specific Immune Response and Viral Clearance: Results of the Biomarker Cohort of a Randomized, Double-Blind, Placebo-Controlled Phase 2b Trial in Non-Hospitalized Patients with COVID-19. Open Forum Infectious Diseases. 2023;10(Supplement 2). doi:10.1093/ofid/ofad500.351

² Paine R, Chasse R, Halstead ES, et al. Inhaled Sargramostim (Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor) for COVID-19-Associated Acute Hypoxemia: Results of the Phase 2, Randomized, Open-Label Trial (iLeukPulm) [published online ahead of print, 2022 Dec 2]. Mil Med. 2022;188(7-8):e2629-e2638. doi:10.1093/milmed/usac362

³ Bosteels C, Van Damme KFA, De Leeuw E, et al. Loss of GM–CSF–Dependent Instruction of Alveolar Macrophages in COVID–19 Provides a Rationale for Inhaled GM–CSF Treatment. Cell Rep Med. 2022:100833. doi: 10.1016/j.xcrm.2022.100833

⁴ Galipeau Y, Greig M, Liu G, Driedger M, Langlois MA. Humoral Responses and Serological Assays in SARS-CoV-2 Infections. Front Immunol. 2020;11:610688. Published 2020 Dec 18. doi:10.3389/fimmu.2020.610688

⁵ Zhou X, Ye Q. Cellular Immune Response to COVID-19 and Potential Immune Modulators. Front Immunol. 2021;12:646333. Published 2021 Apr 30. doi:10.3389/fimmu.2021.646333

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SOURCE Partner Therapeutics, Inc.