Everest Medicines announced top-line results from a China Phase I study on healthy subjects demonstrating that EVER206 (also known as SPR206), a novel intravenous polymyxin derivative in development for the treatment of multi-drug resistant (MDR) gram-negative bacterial infections, is well-tolerated with no evidence of acute kidney injury and no new safety signals on healthy subjects with dose ranges applied in the study. The pharmacokinetics of healthy subjects in China were comparable to the results of the overseas phase I study (SPR206-101) and the safety profile was also similar to the results from the overseas Phase I trial, supporting Everest's plans to initiate next-phase clinical development in China soon. The randomized, double-blind, placebo-controlled phase 1 clinical trial in healthy subjects in China was designed to evaluate the safety, tolerability, and pharmacokinetics of EVER206 administered with single and multiple doses.

A total of 72 subjects were randomized to 6 single-dose cohorts (50mg - 300mg) and 2 multiple-dose cohorts (75mg Q8h and 100mg Q8 h, administered for 7 consecutive days). All enrolled subjects completed dosing per the protocol and completed the trial without dosing interruptions during the study. EVER206 was safe and well tolerated in healthy subjects in all administered doses.

There were no deaths, no serious adverse events and no adverse events that led to termination of study medication or early withdrawal from the study. Most adverse events were mild. The most common TEAE were oral hypoesthesia, dizziness, and nausea.

Only one case of moderate ataxia was observed in the trial, occurring in the single-dose highest-dose 300mg cohort, and two cases with elevated laboratory serum creatinine in the multiple-dose highest-dose 100mg Q8h cohort. All adverse events were reversible, followed by recovery without medical interventions. In an in vitro susceptibility study in China published in 2020, EVER206 showed good in vitro activity against different drug-resistant gram-negative strains.

For MDR isolates of Klebsiella pneumoniae, Escherichia coli, Enterobacter cloacae, Acinetobacter baumannii and Pseudomonas aeruginosa, EVER206 exhibited superior potency, with 2- to 4-fold lower MIC values than colistin and polymyxin B, which indicated higher in vitro potency. Especially for carbapenem-resistant gram-negative bacilli (CRO) with limited treatment options, including Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae, EVER206 showed excellent antibacterial activity in vitro compared to antimicrobial drugs recommended for the treatment of MDR gram-negative infections such as ceftazidime/avibactam. The study results were published in the September 2020 edition of Journal of Antimicrobial Chemotherapy.