Study findings suggest that EVER206 is well-tolerated with no new safety signals, supporting next-phase clinical development in China
SHANGHAI, Jan. 18, 2023 /PRNewswire/ -- Everest Medicines (HKEX 1952.HK, "Everest"), a biopharmaceutical company focused on the development, manufacturing and commercialization of innovative medicines and vaccines, today 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.
"Antibiotic drug resistance is of major concern in China where MDR gram-negative bacterial infections continue to increase over time and create a pressing burden on public health," said Rogers Yongqing Luo, Chief Executive Officer of Everest Medicines. "For patients and the healthcare industry alike, the development of novel treatment options, like EVER206, will be critical. We look forward to advancing EVER206 to late-stage development later this year as a potential best-in-class solution for MDR gram-negative bacteria infections."
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.
"The available polymyxin therapeutics are often reserved as a last line of defense therapy to MDR gram-negative infections. However, toxicity of polymyxins, particularly nephrotoxicity, restricts their use and causes many patients with severe infections to miss out on the treatment," said Sunny Zhu, Chief Medical Officer for Infectious Diseases at Everest Medicines. "We are pleased that the Phase I results suggest that EVER206 may provide a new option for clinical use beyond the safety limitations of polymyxins and can help save the lives of more patients with severe infections."
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.[1]
About EVER206
EVER206 (also known as SPR206) is a potentially best-in-class, novel polymyxin derivative designed to reduce the toxicity, especially nephrotoxicity, compared to that observed clinically with polymyxin B and colistin. Polymyxins are antibiotics frequently used as a last resort for challenging MDR gram-negative infections, but they are associated with significant neurotoxicity and nephrotoxicity. A series of animal studies, in vitro studies and studies in healthy subjects have been completed to-date that demonstrate a favorable safety profile for EVER206 (SPR206) and in-vitro and in-vivo studies indicate the antibacterial activity of SPR206 is similar or superior to polymyxin B or colistin.
Under a licensing agreement with Spero, Everest Medicines has exclusive rights to develop, manufacture and commercialize EVER206 (SPR206) in Greater China, South Korea and certain Southeast Asian countries (the "Territory") for the treatment of MDR gram-negative bacterial infections. Spero granted Pfizer Inc. (NYSE: PFE) the rights to develop, manufacture, and commercialize EVER206 (SPR206) in ex-U.S. and ex-Asia territories in July 2021.
About Everest Medicines
Everest Medicines is a biopharmaceutical company focused on developing, manufacturing and commercializing transformative pharmaceutical products and vaccines that address critical unmet medical needs for patients in Asian markets. The management team of Everest Medicines has deep expertise and an extensive track record from both leading global pharmaceutical companies and local Chinese pharmaceutical companies in high-quality discovery, clinical development, regulatory affairs, CMC, business development and operations. Everest Medicines has built a portfolio of potentially global first-in-class or best-in-class molecules, many of which are in late-stage clinical development. The Company's therapeutic areas of interest include cardio-renal diseases, autoimmune disorders, and infectious diseases. For more information, please visit its website at www.everestmedicines.com.
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[1] Zhang Y, Zhao C, Wang Q, et al. Evaluation of the in vitro activity of new polymyxin B analogue SPR206 against clinical MDR, colistin-resistant and tigecycline-resistant Gram-negative bacilli. Journal of Antimicrobial Chemotherapy. 2020;75(9):2609-2615. |