Clinical potential of DAS181 for treatment of parainfluenza‐3 infections in transplant recipients

Abstract

Parainfluenza virus (PIV) infections can cause serious respiratory infections and death in immunocompromised patients. No antiviral agents have proven efficacy against PIV, and therapy generally consists of supportive care. DAS181, a novel sialidase fusion protein that temporarily disables airway epithelial PIV receptors by enzymatic removal of sialic acid moieties, has been shown to inhibit infection with PIV strains in vitro and in an animal model. We describe here the clinical course of 2 immunocompromised patients with PIV-3 infection, one with a history of lung transplantation and the other neutropenic after autologous hematopoietic stem cell transplantation for multiple myeloma. Both patients had substantial clinical improvement in respiratory and systemic symptoms after a 5-day DAS181 treatment course, although the clinical improvement in the autologous stem cell transplantation patient also paralleled neutrophil engraftment.

Risk Factors for Parainfluenza Virus Lower Respiratory Tract Disease after Hematopoietic Cell Transplantation

“…Steroid use has been consistently shown to be important for progression in this and other studies [11, 17]. Based on our study, we recommend reducing the steroid dose whenever feasible to less than 1 mg/kg when PIV is detected until a new anti-viral drug such as DAS181 or virus-specific T cell therapy are shown to be effective and available for use [26–30]. …”

Parainfluenza virus infections in hematopoietic cell transplant recipients and hematologic malignancy patients: A systematic review

“…[23] DAS181 has shown efficacy against PIV in vitro , in a cotton rat infection model, and in three immunocompromised patients with respiratory infections, including two HCT recipients. [21, 23, 24] Other compounds, such as BCX2798 and BCX2855, have been found to have antiviral activity against PIV-3, significantly reducing pulmonary viral titers and mortality in rats when given intranasally within 24 hours of infection;[22] however, no human studies are available. Given the significant mortality rate associated with PIV-LRTI in immunocompromised patients, there is an unmet need for managing these infections.…”

Blood and Marrow Transplant Clinical Trials Network State of the Science Symposium 2014

“…DAS181 is a novel sialidase viral receptor blocker on respiratory tract epithelial cells [125]. DAS181 is active against several respiratory viruses (including PIV and influenza) [126,127] and is currently in a phase II trial in HCT recipients with PIV LRTD.…”