COVID-19: Solnatide approved for compassionate use

The more COVID-19 patients reach advanced disease stages according to the eight-level WHO disease scale, the more important it becomes to treat life-threatening respiratory distress syndrome (ARDS) or pulmonary edema. Respiratory disease specialist Apeptico Forschung und Entwicklung GmbH has now received compassionate use approval from the Austrian Federal Office for Safety in Health Care for its lead candidate solnatide for the treatment of this COVID-19 patient population. The Phase II candidate drug for the treatment of ARDS and pulmonary edema is designed to help the up to 20% of hospitalized patients who develop life-threatening pulmonary disorders such as ARDS and to counteract the formation of pulmonary edema. The observed mortality rate for ARDS is between 16% and 60%.

According to Bernhard Fischer, Managing Director of Vienna-based Apeptico, "this is the first compassionate use approval of an innovative drug from Austria for the treatment of SARS-CoV-2-induced acute pulmonary dysfunction (ARDS) in mechanically ventilated COVID-19 patients", who have reached disease stage 6 and 7 on the WHO disease scale. "Solnatide will be used to shorten the time of mechanical ventilation," explained Fischer. Lung specialists consider this to be urgently necessary, as intubation and artificial respiration pose considerable health risks.

The Compassionate Use approval of Solnatide closes an important treatment gap. Currently, no drug is approved specifically for the therapeutic treatment of ARDS or pulmonary permeability edema in COVID-19 patients. According to Fischer, however, drugs may neither be sold nor reimbursed under compassionate use. Currently production cost is financed through a Horizon 2020 funding, under which Solnatide is tested in COVID-19 patients, and via financial support from countries, which want to use the drug.

In the long term, however, it would be important to find a strategic development partner, Fischer told European Biotechnology, as ARDS will remain a problem in the future. Until now, the respiratory distress syndrome has been caused mainly by influenza viruses – despite available flu vaccinations and anti-influenza therapy. Now corona viruses that change permanently through mutation are added as a trigger for the syndrome. Therefore an effective therapy is needed to treat the critically ill patients with viral and bacterial pneumonia who develop ARDS, said Fischer. In combination with therapies that help eliminate the cause of the lung damage, solnatide could help to treat various forms of life-threatening acute lung dysfunction and pulmonary oedema.

Solnatide (laboratory code AP301) is a synthetic peptide of less than 20 amino acids. Its application directly in the lower airways in the form of a liquid aerosol is intended to activate the pulmonary sodium ion channels (ENaC) in order to directly activate alveolar fluid clearance and reduce the leakage of blood and fluids from the capillaries in the air space, i.e. accelerate the dissolution of alveolar oedema and reduce barrier damage in the lungs. In addition to alveolar fluid clearance activity, Solnatide inhibits the production of hypoxia-induced reactive oxygen species (ROS) and counteracts various ROS and toxin-mediated effects commonly observed in pneumonia: Solnatide inhibits PKC-alpha activation and thereby restores ENaC activity. The drug reduces the level of myosin light chain phosphorylation (MLC), protects and thus restores the barrier integrity of endothelial and epithelial cells. It has no pro-inflammatory activity and does not lead to increased production of chemokines or increased infiltration of neutrophils.

Inhaled Solnatide has successfully completed the safety assessment of Phase I and two Phase II studies: one in mechanically ventilated ARDS patients with pulmonary edema and a randomized, placebo-controlled pilot study in patients suffering from primary graft dysfunction following lung transplantation.