Leukine Trial in Hospitalized COVID-19 Patients Meets Primary Endpoint

Partner Therapeutics (PTx) announced top-line results of the investigator-led SARPAC (Sargramostim in Patients with Acute Hypoxic Respiratory Failure and Acute COVID-19) study of inhaled Leukine® (sargramostim, yeast-derived recombinant human GM-CSF) in hospitalized COVID-19 patients (NCT04326920). This prospective, randomized, open-label study was led by University Hospital Ghent and conducted at five hospitals in Belgium. The study enrolled 81 patients with PCR-confirmed COVID-19 who were suffering from acute hypoxic respiratory failure requiring supplemental oxygen. The full study and translational results are being prepared for publication.

Lung dysfunction resulting in hypoxemia has been a hallmark of severe cases of COVID-19. SARPAC was launched based on GM-CSF's role in restoring alveolar macrophages that have anti-inflammatory properties and serve to remove pathogens and other debris while maintaining alveolar surfactant. This hypothesis has been the basis for prior studies of sargramostim in Acute Respiratory Distress Syndrome (ARDS). SARPAC was conducted using inhaled sargramostim to target the lungs. Sargramostim is not approved by U.S. Food and Drug Administration (FDA) for use in COVID-19 or for inhaled administration.

"The results from SARPAC represent a major advance for patients with acute hypoxic respiratory failure due to COVID-19 and validate sargramostim's critical role in the repair and healthy functioning of the lung," said Bart Lambrecht, MD, PhD, Professor of Pulmonary Medicine at The University Hospital Ghent, and Scientific Director of the Center for Inflammation Research at the Flanders Institute of Biotechnology (VIB) in Belgium, and principal investigator of the study. "The study confirms sargramostim's role in restoring the oxygen uptake function of the lung, while at the same time stimulating specific immune cells that fight against the virus."

The study met the primary endpoint of improved oxygenation after five days of treatment with inhaled sargramostim in combination with standard of care (SOC) compared with SOC alone. Improvement in oxygenation (as measured by alveolar-arterial oxygen gradient) of at least 33% or more from baseline was seen in 54% of patients on the sargramostim plus SOC arm versus 26% of patients on SOC (p=.0147). Improvements in other lung function measures were also noted.

Sargramostim is a cytokine and an important aspect of the study was to observe whether treatment was safe in COVID-19 patients who may be prone to developing a cytokine storm. Inhaled sargramostim was shown to be well tolerated. Adverse events were generally similar across both arms. There were more nose bleeds on the inhaled sargramostim arm (20% vs 5%) that were mostly mild (grade 1 and 2) and transient. Patients receiving sargramostim showed stable or declining levels of key inflammation markers. These findings support that addition of inhaled sargramostim in these patients does not worsen or induce a "cytokine storm," but rather ameliorates it.

Translational research that accompanied SARPAC showed that sargramostim-treated patients had a statistically significant increase in activation of CD8-positive anti-viral T-cells specifically recognizing the COVID-19 virus. "These CD8 cells get activated when they see the virus, and the type of CD8 T-cells we observed are generally seen when you give a vaccination against a virus," Lambrecht said. "On top of that, we also observed virus-specific CD4 helper cells being induced. The biomarker studies will include the effect of sargramostim in lowering the levels of markers for lung damage and lung fibrosis that has been noted to be elevated in COVID-19 'long haulers'."

SARPAC results are consistent with data from earlier studies of sargramostim in ARDS that demonstrated positive impact on lung health.

"Prior research in patients with acute respiratory distress syndrome has shown that sargramostim administered intravenously is safe and associated with a trend toward a reduction in mortality. The findings from SARPAC provide strong support for further clinical research to assess the safety and efficacy of inhaled sargramostim in the treatment of COVID-19," said Dr. Robert Paine, Chief of the Division of Pulmonary Medicine at the University of Utah, adding, "I believe that administering sargramostim by inhalation as soon as patients are being treated in an inpatient or outpatient setting due to COVID-19 could improve time to recovery and facilitate long-term healing."

In addition to the SARPAC study, inhaled sargramostim is being assessed in the iLeukPulm study, a 120 patient, 2:1 (sargramostim plus standard of care vs. standard of care) randomized study conducted at 11 sites in the United States (NCT04411680). This study is similar in design to SARPAC, assessing the ability of inhaled sargramostim to improve oxygenation in patients hospitalized for COVID-19. Enrollment has concluded in the study and results are expected in Q2 2021. Based on the potential for sargramostim to stimulate immune cells targeting the SARS-CoV-2 virus, irrespective of strain, PTx is also launching the SCOPE trial to evaluate sargramostim in a trial of 400 COVID-19 patients in an outpatient setting (NCT04707664). These studies are supported by the U.S. Department of Defense's (DoD) Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND).

"PTx is heartened that this study shows Leukine's potential to help patients in the midst of this pandemic," said Dr. Debasish Roychowdhury, Chief Technology Officer at Partner Therapeutics. "We are deeply grateful for the work being done by the clinical research teams in Belgium and for the patients who have participated in the SARPAC trial. Similarly, we are grateful to the US investigators and patients on the iLeukPulm study. We look forward to learning the results from that study and to full publication of the data from both SARPAC and iLeukPulm."

LEUKINE® (sargramostim) is a yeast-derived recombinant human granulocyte-macrophage colony stimulating factor (rhuGM-CSF) Leukine is approved by the FDA and is also held by the U.S. Government in the Strategic National Stockpile. Leukine is available outside of the United States through a Named Patient Program administered by Tanner Pharma Group.