APEIRON Biologics’ potential COVID-19 therapeutic
Covid-19 is a complex and dynamic disease with severe symptoms and long sequelae is predicted to become endemic with approximately 100 million cases a year, despite the rollout of vaccines and therapies, many of which have failed. The Vienna BioCenter’s APEIRON has long worked on a drug candidate that could be a possible therapeutic.
APEIRON Biologics AG, a privately held biotech company developing breakthrough therapies to treat cancer and respiratory conditions at the Vienna BioCenter, announced on 12 March 2021 that its proprietary APN01 (alunacedase alfa) drug candidate showed statistically significant improvements in specific areas for severely ill Covid-19 patients. The multi-center, double-blind, randomized, placebo-controlled, interventional phase 2 trial performed in Austria, Denmark, Germany and Russia assessed the safety, tolerability and efficacy of APN01 in 178 patients with moderate to severe COVID-19 compared to placebo (clinical trials.gov NCT04335136). Both groups also additionally received standard of care. APEIRON’s APN01 drug candidate is a soluble recombinant human Angiotensin Converting Enzyme 2 (rhACE2) which mimics ACE2, a receptor identified as the critical cellular entry receptor for the SARS-CoV-2 virus and therefore plays a crucial role in combating COVID-19
For the primary endpoint of the trial, a composite endpoint of all-cause death or invasive mechanical ventilation up to 28 days or until hospital discharge, it was shown that fewer patients treated with APN01 (n=9) died or received invasive ventilation compared to placebo (n=12), although statistical significance was not achieved due to the low total number of events.
Treatment with APN01 was safe and well tolerated and no drug-related severe adverse events were observed during the study. The data demonstrated a statistically significant improvement in mechanical ventilator-free days in alive patients and reduction in viral load in APN01 group versus placebo (secondary endpoints). APN01 also demonstrated a positive impact on key biomarkers of the renin angiotensin system (RAS), demonstrating in vivo efficacy of the drug. Further supporting data evaluated APN01 treatment according to the WHO 11-Point score system, which sets outcome measures to assess a patient’s clinical burden of COVID-19 infection. These data showed improvements in important clinical parameters.
Throughout the trial, plasma levels of Ang II, a pro-inflammatory and vasoconstrictive factor in RAS were significantly reduced under APN01 treatment. APN01 treatment was shown to significantly increase Ang 1-7 and Ang 1-5 levels while no increase seen in the placebo group. These findings support the mode of action of APN01 revealed in previous phase 1 and 2 clinical trials in patients with acute lung injury (ALI), acute respiratory distress syndrome (ARDS) and pulmonary arterial hypertension (PAH). Lung injuries caused by ARDS are one of the major symptoms of severe COVID-19. Importantly, with the recent emergence of virus variants that can escape antibody drugs and even vaccines but cannot escape binding to its receptor and “entry door” ACE2, APN01 could become a critical drug in the global therapy repertoire against virus variants.
APN01 was first discovered and developed by the founder of APEIRON Biologics Josef Penninger in response to the first SARS outbreak in 2003.