Partner Therapeutics Announces $35 Million Contract with U.S. Department of Defense for Advanced Development and Emergency Use of Leukine® (rhuGM-CSF) for COVID-19 Acute Hypoxemic Respiratory Failure (AHRF)
LEXINGTON, Mass., Aug. 4, 2020 /PRNewswire/ -- Partner Therapeutics, Inc. (PTx), a commercial biotechnology company, today anounced a $35 million milestone-based Other Transaction Agreement (OTA) with the U.S. Department of Defense (DOD) to fund two clinical studies of inhaled Leukine® (sargramostim, rhu-Granulocyte Macrophage-Colony Stimulating Factor "GM-CSF") in patients with COVID-19 associated acute hypoxemia. Through the DOD's Chemical Biological Defense Program COVID-19 efforts, the Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense's (JPEO-CBRND) will evaluate the effect of Leukine in improving clinical outcomes, including oxygenation and percent of patients intubated. The first of the two clinical studies (NCT04411680) will be initiated in August 2020 in centers in the U.S., and will be conducted under an Investigational New Drug (IND) Application, approved by the U.S. Food and Drug Administration (FDA) on May 20, 2020.
The milestone-based Firm Fixed Price (FFP) agreement with the JPEO-CBRND will fund two Phase 2 studies to assess the benefits of Leukine in the treatment of patients with acute hypoxemia due to COVID-19. Funding will also support regulatory filings for a potential EUA and expansion of production capacity to meet increased demand. The first of the two clinical studies will commence in August 2020 and will supplement data from more than 60 patients who have completed treatment in the SARPAC study (sargramostim in patients with acute hypoxic respiratory failure due to COVID-19) clinical trial, currently underway at five hospitals in Belgium (NCT04326920).
"GM-CSF is essential for lung health. Emerging data suggest that COVID-19 is associated with immune dysfunction including deficiency of alveolar macrophages and GM-CSF," said Dr. Debasish Roychowdhury, chief medical officer at PTx. "Treatment with Leukine may confer benefit to patients with acute respiratory distress and potentially reduce long term complications. We are grateful to the DOD's JPEO-CBRND for supporting this effort to assess the potential role of Leukine to treat patients with severe COVID-19 infection. Effective, safe and easily administered treatments that halt or reverse the progression of the disease and reduce the risk of long term complications represent an area of significant unmet need in treatment of COVID-19."
In March 2020, PTx announced that Leukine is being assessed in the SARPAC clinical trial currently underway in Belgium to treat patients with respiratory illness associated with COVID-19 (NCT04326920). The SARPAC study is the first randomized, controlled clinical trial to assess the benefits of Leukine via inhalation in the treatment of COVID-19. In May, Singapore General Hospital also initiated a study of intravenous Leukine in COVID-19 patients (NCT04400929).
"The DOD's support enhances Partner Therapeutics' efforts to rapidly advance the study of Leukine as a treatment to halt COVID disease progression and mitigate long-term organ damage and other complications," said John McManus, chief business officer of PTx. "Leukine has a proven safety profile and there is clinical evidence indicating that it could confer benefit to patients with acute hypoxemia from COVID-19 infection. We look forward to working with JPEO-CBRND to deliver our milestones expeditiously under this agreement."
"We are pleased to work with Partner Therapeutics and excited about the prospects of repurposing already FDA-approved medical countermeasures for the fight against COVID-19," said the JPEO-CBRND's Joint Project Manager for CBRN Medical, Col. Ryan Eckmeier. "Proving a repurposing framework for treating acute hypoxemic respiratory failure is particularly useful to our core mission of protecting our nation's warfighters from CBRN threats, as AHRF is a condition which can also occur with exposure to other CBRN agents."
Leukine is FDA-approved for the treatment of acute radiation syndrome (ARS) and is held in the Strategic National Stockpile. "The potential utility for COVID patients highlights Leukine's promise as a broad-spectrum, dual-use medical countermeasure," added McManus.
Leukine was first approved by the FDA in 1991 and has an established safety profile based on treatment in more than 500,000 patients. The use of Leukine to treat respiratory disorders associated with COVID-19 is investigational and has not been fully evaluated by any regulatory authority.
ABOUT LEUKINE
LEUKINE(R) (sargramostim) is a recombinant human granulocyte-macrophage
colony stimulating factor (rhuGM-CSF) that stimulates the differentiation,
maturation and mobilization of cells involved in the innate and adaptive
immune response. It has been shown to facilitate cellular signaling,
epithelial repair and other critical processes that enhance the immune
response and help defend the body against infection and cancer. Partner
Therapeutics acquired the rights to Leukine in 2018. Leukine is approved by
the FDA. Leukine also is held by the U.S. Government in the Strategic
National Stockpile and available outside of the United States through a
Named Patient Program administered by Tanner Pharma Group.
ABOUT GM-CSF IN THE LUNG
GM-CSF is a naturally occurring protein that is essential for maintaining
healthy lungs. GM-CSF intrinsically controls resident alveolar macrophages
as well as the differentiation and maturation of monocytes into alveolar
macrophages. Alveolar macrophages function like the vacuum cleaners of the
lung by removing cellular debris, particulate material and pathogens.1,2 GM-
CSF leads the immune functions of alveolar macrophages and dendritic cells
through activation of both the innate and adaptive immune responses.
Following a pulmonary viral infection, activation of both immune systems
accelerates viral clearance. Through direct interaction with alveolar
epithelial cells, GM-CSF also improves epithelial repair processes during
lung injury. In response to infection, GM-CSF is released from alveolar
epithelial cells in an autocrine manner to stimulate epithelial repair and
barrier restoration.3 Additionally, alveolar macrophages maintain the
homeostasis of surfactant, a substance that coats the inside of alveoli (air
sacs) to prevent them from collapsing, and play an anti-inflammatory role
by removing dying neutrophils that infiltrate the space and reducing pro-
inflammatory cytokine secretion by macrophages.1-3 Alveolar macrophages can
limit the antigen-specific functional responsiveness of T cells in the
lung, reducing local pulmonary inflammation.4
Of note, GM-CSF has a different mechanism of action from G-CSF (granulocyte
colony stimulating factor) and the drugs should not be used interchangeably.
ABOUT GM-CSF IN COVID-19
The SARS-CoV-2 virus infects and damages the cellular lining of the
lungs.5-7 This is associated with diffuse alveolar damage, severe
endothelial injury with the presence of intracellular virus and disrupted
cell membranes.8 The alveolar macrophages that are crucial for the removal
of cellular debris are almost completely destroyed in the severely-infected
lungs of patients with COVID-19.9 Breakdown of the epithelial barrier
promotes capillary leakage and further lung damage.5-7 Control of viral
spread depends on interactions between epithelial cells and immune cells,
mediated by cytokine signaling and cell-cell contacts. After viral
clearance, activated immune cells and debris must be eliminated to avoid
hyperactivation of the immune system that can further exacerbate lung
epithelial damage.10 The extensive lung epithelial damage observed in
patients with COVID-19 compromises gas exchange which may progress to acute
respiratory distress.9
GM-CSF is an immune mediator that drives pulmonary host defense function and
stimulates epithelial repair.(3) GM-CSF is critical for the growth,
maturation, replenishment and function of alveolar macrophages.3,11 GM-CSF,
through its effects on alveolar macrophages, has been shown to accelerate
respiratory viral clearance.3,12,13 Unchecked viral replication in the
respiratory tract could be a result of inefficient innate anti-viral immune
response.14,15 Further cases of immune dysfunction, marked by low levels of
both eosinophils and functional lymphocytes, have been reported in patients
with COVID-19.16,17 Systemic elevation of pro- and anti-inflammatory
cytokines in severe illnesses can sometimes lead to suppression of
circulating leukocyte function, or "immunoparalysis."18-20 GM-CSF has been
shown to overcome the immunoparalysis observed in critically ill
patients.21,22 Therefore, GM-CSF treatment may exert a local effect on
restoration of lung health and function and a systemic effect by resuming
immune homeostasis.3,23
ABOUT LEUKINE CLINICAL TRIALS IN COVID-19
In addition to the U.S. study described in this press release, Leukine is
being evaluated in clinical trials in Belgium and Singapore.
The SARPAC study (Sargramostim in Patients with Acute Hypoxic Respiratory
Failure and Acute COVID-19) is a prospective, randomized, open-label
controlled study designed to assess whether inhaled Leukine (sargramostim)
can restore lung function and other clinical outcomes in COVID-19 patients
experiencing acute hypoxemia (NCT04326920). The study is open to
hospitalized patients age 18-80 with a confirmed diagnosis of COVID-19
infections and symptoms of low oxygenation (O2 saturation <93% on minimal 2
L/min O2 and/or PaO2/FiO2 <350). The primary endpoint is improvement in
oxygenation following five days of Leukine + standard of care (SOC) or with
SOC alone, as measured by pre- and post- treatment PaO2/FiO2 ratios and
the alveolar-arterial (P(A-a)) gradient. This study is underway at
multiple sites in Belgium and is led by Dr. Bart Lambrecht at University
Hospital Ghent in Belgium.
---
The Singapore trial, titled "Using GM-CSF as a host directed therapeutic
against COVID-19 - a Phase 2 Investigator Initiated Trial" is open to
hospitalized patients ages 21-80 with acute hypoxic respiratory failure (O2
saturation <94% on minimal 2 L/min O2 and/or PaO2/FiO2 <350) due to
COVID-19 who are randomized to receive Leukine intravenously for five days
in addition to local SOC (treatment arm) or SOC alone (placebo group)
(NCT04400929). The primary endpoint is the difference in the mean change in
oxygenation (P[A-a]O2 gradient) between the two groups at day six compared
to day one. The study is led by Dr. Jenny Guek Hong Low, Senior Consultant,
Department of Infectious Diseases, Singapore General Hospital.
ABOUT PARTNER THERAPEUTICS
PTx is an integrated biotechnology company focused on the development and
commercialization of late-stage therapeutics that improve health outcomes
in the 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) protects the Joint Force by providing medical
countermeasures and defense equipment against chemical, biological,
radiological and nuclear (CBRN) threats. JPEO-CBRND's goal is to enable the
Joint Force to fight and win unencumbered by a CBRN environment. JPEO-CBRND
facilitates the rapid response, advanced development, manufacturing and
acquisition of medical solutions, such as vaccines, therapeutics, and
diagnostics, to combat CBRN and emerging threats such as COVID-19. To learn
more about JPEO-CBRND's COVID-19 response, visit https://
www.jpeocbrnd.osd.mil/coronavirus or follow JPEO-CBRND on social media at
@JPEOCBRND.
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