Sorrento Therapeutics announces encouraging results from two phase II studies of abivertinib.

Abivertinib is a novel small molecule tyrosine kinase inhibitor (TKI) that selectively targets both mutant forms of the epidermal growth factor receptor (EGFR) as well as Bruton's tyrosine kinase (BTK). 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 with potent inhibition of key pro-inflammatory cytokine production, including IL-1 beta, IL-6 and TNF-alpha. These cytokines are associated with acute respiratory distress syndrome (ARDS), and with cytokine release syndrome (CRS) or cytokine storm, and COVID-19 disease progression with poor outcomes in patients.

The US study, entitled “A Phase II, 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),recently completed enrollment (N=96 randomized 1:1). The Brazil study, entitled “A Phase II, Randomized, Double-Blind, Placebo-controlled Study of the Safety and Efficacy of STI-5656 (Abivertinib Maleate) in Subjects Hospitalized Due to COVID-19” also completed enrollment (N=400, randomized 3:1 active vs. placebo). Both studies were designed to assess the potential clinical benefits of Abivertinib’s ability to reduce inflammatory cytokine storm associated with COVID-19-induced respiratory depression. It was also important to identify the potential patient population most likely to respond to treatment based upon severity of COVID-19 respiratory depression at baseline. In both studies the clinical status was assessed using a 9-point (0 to 8) categorical scale, where 3=hospitalized with no oxygen therapy, 4=hospitalized with oxygen by mask or nasal cannulae, 5=non-invasive ventilation or high flow oxygen, 6=intubation and mechanical ventilation, 7=additional organ support such as extracorporeal membrane oxygenation, and 8=death.

In the US Abivertinib study most patients (57%) were sicker at baseline (category 5 clinical status) with patients in the Abivertinib group skewed to sicker or worse severity by clinical status (Abivertinib Group: 29/48: 60% vs. Control Placebo Group: 26/48: 38% for category 5, respectively) and by oxygenation status (P/F ratio 211 vs. 253, respectively). In the Brazil Abivertinib study , only 8% were in category 5, demonstrating a far less severely compromised population having been enrolled.

In the US study, patients in category 5 showed a 20% improvement in the primary endpoint, and in the Brazil study, a 25% improvement In the US study, patients in category 5 treated with Abivertinib were discharged from the hospital 2 days sooner than those in the Control Group (8.6 vs. 10.6 days). Overall, in both studies patients who were in category 5, but not in category < 4, showed improvement with Abivertinib treatment. Based upon these preliminary results, a pivotal multi-country, multi-center pivotal Phase III study is being planned in 400 patients (randomized 1:1) on the At-Risk Hospitalized COVID-19 Patients requiring oxygen support via non-invasive ventilation or high flow oxygen at baseline (category 5 patients).