Acute Respiratory Distress Syndrome

ARDS

Acute respiratory distress syndrome (ARDS) is a life-threatening condition in which fluid collects in the alveoli (air sacs of the lungs), depriving organs of oxygen. 1

Patients with ARDS have severe, debilitating shortness of breath and often require ventilation. ARDS usually occurs in those who are critically ill or who have significant injuries.1,2

The mainstay interventions are supportive lung protective ventilation and prone positioning. The mortality rate for ARDS is 30-40%, and few effective therapeutic modalities exist to ameliorate this life-threatening condition.2,3

Following the onset of ARDS the ensuing acute inflammation and tissue injury result in structural changes in the lungs, this is called adverse tissue remodelling. As ARDS progresses, adverse tissue remodelling obstructs efficient lung function resulting in hypoxia which requires frequent oxygen ventilation to normalise blood oxygen levels.2,4

ARDS survivors may experience post-traumatic stress disorder, post-intensive care syndrome, long-term physical disability, neuromuscular weakness and persistent pulmonary dysfunction.2,5

In 2016, ARDS occurrence was estimated to be 10.4% in all ICU admissions and accounted for 23.4% of mechanically ventilated patients globally.6

Acute Respiratory
Distress Syndrome

ARDS

Acute respiratory distress syndrome (ARDS) is a life-threatening condition in which fluid collects in the alveoli (air sacs of the lungs), depriving organs of oxygen. 1

Patients with ARDS have severe, debilitating shortness of breath and often require ventilation. ARDS usually occurs in those who are critically ill or who have significant injuries.1,2

The mainstay interventions are supportive lung protective ventilation and prone positioning. The mortality rate for ARDS is 30-40%, and few effective therapeutic modalities exist to ameliorate this life-threatening condition.2,3

Following the onset of ARDS the ensuing acute inflammation and tissue injury result in structural changes in the lungs, this is called adverse tissue remodelling. As ARDS progresses, adverse tissue remodelling obstructs efficient lung function resulting in hypoxia which requires frequent oxygen ventilation to normalise blood oxygen levels.2,4

ARDS survivors may experience post-traumatic stress disorder, post-intensive care syndrome, long-term physical disability, neuromuscular weakness and persistent pulmonary dysfunction.2,5

In 2016, ARDS occurrence was estimated to be 10.4% in all ICU admissions and accounted for 23.4% of mechanically ventilated patients globally.6

Key ARDS Figures

Global % ICU admissionss6
10.4 %
Global % mechanically ventilated patients6
23.4%
Global overall hospital mortality rate6
40%

Key ARDS Figures

Global % ICU admissionss6
10.4 %
Global % mechanically ventilated patients6
23.4%
Global overall hospital mortality rate6
40%

Drug in development

Pentosan
Polysulfate
Sodium

Mechanism of Action

Paradigm’s rationale for the use of pentosan polysulfate sodium to target ARDS is based on its multiple mechanisms of action outlined in preclinical studies. The mechanisms of action of PPS that are relevant to modulating the pathophysiology of ARDS include:

- Targeting the cytokine storm response via anti-inflammatory effects mediated by the inhibition of NF-κB7
- Inhibition of complement activation, which is involved in lung tissue degeneration 8
- Inhibition of ADAMTS-4 activity, which is likely to be involved in adverse tissue remodelling 9-11

Remodelling
Inflammation

Development milestones

A preclinical proof-of-concept study in a mouse model of ARDS mediated by influenza infection conducted at the Menzies Health Institute in Queensland has provided evidence that PPS may have potential for the treatment of virus-induced inflammatory conditions such as ARDS.

Paradigm is interested in exploring strategic partnerships for commercialisation of PPS as a treatment for osteoarthritis.
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