SARPAC Clinical Trial of Leukine in Hospitalized COVID-19 Patients Meets Primary Endpoint of Significant Improvement in Lung Function
1 March 2021 - - US-based biotechnology company Partner Therapeutics, Inc. has released 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), the company said.

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.

SARPAC was conducted using inhaled sargramostim to target the lungs. Sargramostim is not approved by US Food and Drug Administration for use in COVID-19 or for inhaled administration.

The study met the primary endpoint of improved oxygenation after five days of treatment with inhaled sargramostim in combination with standard of care 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.

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

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 US Department of Defense's Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND).

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 US government in the Strategic National Stockpile. Leukine is available outside of the United States through a Named Patient Program administered by Tanner Pharma Group.

Safety and efficacy of inhaled sargramostim for the treatment of COVID-19 has not been established and sargramostim is not approved for the treatment of COVID-19. 

Sargramostim has a different mechanism of action from recombinant G-CSFs products and data should not be extrapolated.

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.