Ampio Pharmaceuticals is preparing an expanded access US FDA protocol to study potential benefit of nebulised treatment with Ampion in COVID-19-induced acute respiratory distress syndrome (ARDS), an immediately life-threatening condition.
Separately, the company has halted a Phase III clinical trial of the product in elderly patients with osteoarthritis, in light of the risk posed to these patients by the COVID-19 outbreak.
Ampio Scientific Advisory Board members David Bar-Or, MD, Pablo Rubinstein, MD, and Edward Brody, MD, PhD, determined after a careful review of the published articles on the properties of Ampion, that nebulised Ampion may be suitable to treat another inflammatory indication. Specifically, ARDS, one of the most dreaded complications of COVID-19 is associated with widespread inflammation in the lungs. The underlying mechanism of ARDS involves diffuse injury to cells which form the barrier of the microscopic air sacs (alveoli) of the lung, surfactant dysfunction, and activation of the immune system. The fluid accumulation in the lungs associated with ARDS is partially explained by vascular leakage due to inflammation. Ampion is an aqueous solution that may be delivered through nebulisation and may be suitable for suppressing inflammation in the lungs.
Ampion is a human blood derived composition, currently approved for clinical use by the FDA, as an anti-inflammatory, immunomodulating drug. The novel mode of action of Ampion involves multiple biochemical pathways associated with resolving inflammation1 which make it a potential therapy for ARDS as follows:
- An important aspect of ARDS, triggered by COVID-19, is an initial release of chemical signals and other inflammatory mediators secreted by lung epithelial and endothelial cells. neutrophils and some T-lymphocytes migrate into the inflamed lung tissue and contribute to the amplification/deterioration of ARDS. A decrease in the production of lipid mediators of inflammation (prostaglandins) may impair the resolution of inflammation associated with ARDS2,3.
- Ampion was reported to up regulate the production of these healing lipid mediators’ prostaglandins in vitro3. In addition, multiple inflammatory signals (i.e. TNF α, IL6, CXCL10) have been reported to be attenuated by Ampion, including a decrease in vascular permeability.
- If Ampion is found to be an efficacious treatment for COVID-19 induced ARDS, the Company’s in-house manufacturing facility may allow the product to be produced quickly and in significant quantities.
The anticipated aim of a preliminary protocol for FDA review would be to evaluate patients with moderate to severe ARDS, triggered by COVID-19, for (a) reduced ventilator time; (b) reduction in mortality and (c) improvements in oxygenation parameters compared to non-Ampion treated patients.
- Bar-Or et al, “On the Mechanisms of Action of the Low Molecular Weight Fraction of Commercial Human Serum Albumin in Osteoarthritis”. Current Rheumatology Rev, 2019, Vol 15, pp 189-200.
- Fukunaga et al, “Cyclooxygenase 2 Plays a Pivotal Role in the Resolution of Acute Lung Injury”. J Immunol, 2005, Vol 174, ppp 5033-5039.
- Gao et al, “Resolvin D1 Improves the Resolution of Inflammation via Activating NF-κB p50/p50-Mediated Cyclooxygenase-2 Expression in Acute Respiratory Distress Syndrome”. J Immunol, 2017, Vol 174, pp 5033-5039.
Source: OINDP News.
Link to Press Release.