COVID-19 Investigational Therapy Approved for Phase 2 Study

The FDA clears way for next phase for abivertinib to treat hospitalized patients.

Abivertinib, an investigational COVID-19 therapy, was cleared by the Food and Drug Administration (FDA) for a Phase 2 study for efficacy and safety for hospitalized COVID-19 patients who have moderate to severe pulmonary symptoms.

Specifically, the research is going to look at hospitalized patients who have developed a cytokine storm in the lungs.

According to some reports, patients’ immune systems can overreact to COVID-19 and cause a cytokine storm, which elevates levels of inflammatory molecules that damage healthy cells.

During in-vitro studies, abivertinib demonstrated an ability to lower multiple critical inflammatory cytokines associated with cytokine storm and poor prognosis in COVID-19 patients.

Abivertinib is a novel small molecule tyrosine kinase inhibitor (TKI) that selectively targets both mutant forms of the epidermal growth factor receptor (EGFR) and Bruton's tyrosine kinase (BTK).

In terms of its mechanism of action, abivertinib irreversibly binds to the BTK receptor, preventing the phosphorylation of the receptor. Due to this effect, it has shown potent immunomodulatory activities in vitro by inhibiting key pro-inflammatory cytokine production, including IL-1beta, IL-6 and TNF-alpha.

These cytokines are associated with cytokine release syndrome (CRS) or cytokine storm and COVID-19 disease progression with poor outcomes in patients with acute respiratory distress syndrome (ARDS).

This Phase 2 trial will be titled, Double Blinded, Randomized Study of the Efficacy and Safety of STI-5656 (Abivertinib Maleate) With Standard of Care Versus Standard of Care in Subjects Hospitalized With COVID-19 (NCT04440007).

This will be a US-based trial and conducted in medical centers within the country.

Abivertinib has already been studied in over 600 patients internationally in various oncologic indications, including one registration trial in non-small cell lung cancer. Most treatment-related adverse events (AEs) were grade 1 or 2, the most common of which were transaminase elevations and diarrhea, which are generally considered common for TKIs. Other common treatment-related AEs included anemia, neutropenia and thrombocytopenia, each of which are generally considered typical AEs with long-term use of TKIs. No unexpected AEs were reported.

Abivertinib was developed by ACEA Therapeutics. The compound is currently under review by the China Food and Drug Administration (CFDA) for the treatment of patients with non-small cell lung cancer (NSCLC) containing the EGFR T790M mutation. Along with this compound and other R & D initiatives, ACEA has established drug manufacturing in China to support its long-term growth.

ACEA has partnered with San Diego-based Sorrento Therapeutics, which is a clinical stage, antibody-centric, biopharmaceutical company developing new therapies to treat cancers and potential antiviral therapies and vaccines against coronaviruses.

Back in May, Sorrento announced that it had entered into a binding term sheet for an exclusive license to ACEA's abivertinib across all indications for all territories outside of China. The parties have since entered into an exclusive license agreement.