Pulmocide announces the initiation of a study to assess the anti-viral effect, safety and tolerability of inhaled PC786 for the treatment of acute respiratory syncytial virus (RSV) infection in adult hematopoietic stem cell transplant recipients. This is a multi-centre, double blind, randomised, placebo-controlled study to assess the anti-viral effect, safety, tolerability and pharmacokinetics of inhaled PC786 in adult HSCT recipients with acute RSV infection.
PC786 is a non-nucleotide inhibitor of RSV polymerase which inhibits replication of both the A and B subtypes of RSV, thus interrupting the spread of infection within the respiratory tract*. Administration of PC786 via inhalation results in high local concentrations in the airway, directly at the site of viral replication, with low systemic exposure and hence a low risk of systemic side effects. PC786 demonstrates excellent safety and tolerability in phase 1 studies. Pre-clinical and clinical pharmacokinetic data demonstrate low systemic concentrations with prolonged lung retention.
RSV infection in HSCT recipients
Respiratory syncytial virus (RSV) is a single-stranded, negative-sense ribonucleic acid (RNA) virus and a member of the family of Pneumoviridae of the Mononegavirales order. Respiratory syncytial virus is the most common cause of childhood acute lower respiratory infection, and may result in life threatening disease in patients of any age. Infants, the elderly, as well as those patients with compromised cardiac, pulmonary or immune systems are particularly vulnerable. In addition, RSV infection is increasingly implicated as a cause of exacerbations in patients suffering from chronic obstructive pulmonary disease, asthma and cystic fibrosis.
Respiratory syncytial virus infections occur in up to 12% of adult patients with haematological malignancy or who have undergone hematopoietic stem cell transplant (HSCT). Respiratory syncytial virus causes significant morbidity and mortality in adult patients with haematological diseases when upper respiratory tract infection (URTI) progresses to lower respiratory tract infection (LRTI). Progression from URTI to LRTI is associated with high rates of morbidity and mortality.
Treatment options for RSV-infected adults are limited. Ribavirin has been approved for the treatment of severe RSV infections in infants and children, but has not been approved for treatment of RSV in adults. New treatment options are urgently required.
* Preclinical characterization of the inhaled small molecule respiratory syncytial virus L-protein polymerase inhibitor, PC786 M Coates et al, Antimicrob. Agents Chemother. 2017 Aug 24;61(9)
Late therapeutic intervention with a respiratory syncytial virus L-protein polymerase inhibitor, PC786, on RSV infection in human airway epithelium. Brookes D et al, Br J Pharmacol. 26 March 2018 https://doi.org/10.1111/bph.14221