In April 2020, APEIRON Biologics initiated a phase II trial to assess safety and tolerability of APN 01 in patients with COVID-2019 infections (APN01-01COVID19; EudraCT2020-001172-15; NCT04335136). The primary objective of the trial is to assess the clinical efficacy and safety of APN 01 in severe COVID-19 patients using the need for invasive mechanical ventilation. Secondary objectives include the evaluation of measurable biological biomarker changes following treatment with APN 01. The randomised, double-blind trial has initiated enrolment of approximately 200 patients in Austria, Germany, Denmark, and the United Kingdom, and is expected to expand to other countries including the US, Canada and Russia   .
APEIRON Biologics and University of British Columbia, in February 2020, reported of the initiation of a pilot investigator-initiated clinical trial, designed to evaluate APN 01, in patients with severe COVID-2019 infections. The unblinded study is expected to enrol approximately 24 patients in China. Data from the study is expected to support a potential phase IIb study in larger patient population  .
In 2019, APEIRON obtained the licenses related to APN 01 back from GlaxoSmithKline (GSK) for further clinical development, after a strategic refocusing of GSK to oncology. As per APEIRONs' pipeline APN 01 is still in phase II development for acute lung injury and pulmonal arterial hypertension  .
As at July 2019, GlaxoSmithKline decided to discontinue the development of GSK 2586881(GlaxoSmithKline pipeline July 2019).
In May 2019, GlaxoSmithKline completed a phase IIa dose escalation study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of GSK 2586881 in patients with pulmonary arterial hypertension (206246; NCT03177603; EudraCT2017-000212-41). The open-label, parallel trial initiated in February 2018 and enrolled 23 patients in Spain, Germany and USA  .
GlaxoSmithKline completed a phase IIa trial in the US and Canada, which evaluated the tolerability, safety, pharmacokinetics and pharmacodynamics of GSK 2586881 in 44 patients with acute respiratory distress syndrome or acute lung injury, in October 2014 (NCT01597635; 114622). The trial was initiated in September 2012 and was conducted in two parts; an open-label phase and a double-blind, placebo-controlled phase   .
In January 2019, GlaxoSmithKline terminated a phase I trial due to technical feasibility, operational considerations and futility in line with pre-specified criteria, that was designed to evaluate the effect of a single IV dose of GSK 2586881 on the acute hypoxic pulmonary vasoconstriction response, in healthy volunteers (204987; NCT03000686). The single-centre, randomised, crossover, placebo-controlled, double-blind trial intended to enrol approximately 25 volunteers in Germany  .
In December 2009, Apeiron completed a phase I trial of GSK 2586881 in 22 healthy volunteers in Switzerland (NCT00886353; APN01-1-01). The trial determined the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple intravenous doses of GSK 2586881. In the single dose, dose escalation part, four cohorts received GSK 2586881 (100, 200, 400 or 800 µg/kg) or placebo. In the multiple dose part, two cohorts received three and six administrations of GSK 2586881 daily, respectively; the planned dosage was 400 µg/kg. Study results showed GSK 2586881 to be safe; no side effects or toxicities were found   .
In an ex vivo study, treatment with GSK 2586881 of undiluted heparinised plasma samples or effusions of patients with cancer resulted in the reduction of elevated angiotensin II. Apeiron filed for an application to initiate a clinical trial of GSK 2586881 in patients with advanced cancer; however, no recent development has been reported for this indication  .
Promising data from GSK 2586881 in murine models of hypertension were presented at the 18th European Society of Hypertension and the 22nd Scientific Meeting of the International Society of Hypertension Sessions (HYP-2008)  . However, no recent development has been reported for this indication.
In March 2020, Apeiron Biologics withdrawed a clinical trial prior to enrollment, as there was no CDE Approval. The trial was designed to evaluate APN 01 in adult patients with COVID-19 infections (GIRH-APN01; NCT04287686). The randomised, open label, controlled clinical study intended to enrol patients in China  .