Spexis AG announced positive results from the first-in-human clinical trial of the novel antibiotic murepavadin, a macrocycle compound derived using Spexis’ proprietary platform. It is delivered via oral inhalation and designed to target the outer membrane of the key pathogen found in cystic fibrosis (CF) lung infections, Pseudomonas aeruginosa.

A total of 39 individuals took part in this single-center, double-blind, randomized, placebo-controlled trial aimed at investigating the safety, tolerability, and pharmacokinetics of inhaled murepavadin in healthy volunteers.

Part A of the trial evaluated 3 single-dose levels (12.5 mg, 25mg, and 50 mg) of inhaled murepavadin in 4 participants per cohort. In Part B, single doses of 75 mg, 150 mg, and 300 mg were given to 9 patients per cohort. The pharmacokinetics of inhaled murepavadin were analyzed in blood samples as well as epithelial lining fluid obtained by bronchoalveolar lavage.

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According to the trial data, inhaled murepavadin was well tolerated at all dose levels and there were no reports of serious adverse events or signs of upper airway irritation. The serial pulmonary function test results showed no narrowing of the airways upon the medication administration. In addition, electrocardiogram and safety laboratory test results and vital signs remained normal.

Moreover, systemic bioavailability of inhaled murepavadin was lower than 5%, and peak plasma concentrations were observed at 1-2 hours after the start of inhalation. The concentration of the medication measured in the epithelial lining fluid 24 hours after dosing was still above the concentration that would inhibit the growth of 90% of P isolates (MIC90) obtained from people with CF.

“The first clinical data with our inhaled murepavadin hold promise as we work to bring more efficacious and safe treatments for serious lung infections to patients in need, including people with cystic fibrosis and non-CF bronchiectasis,” Juergen Froehlich, MD, chief medical officer of Spexis, stated in a press release.

The high inhibiting concentrations paired with favorable tolerability and safety profiles offer possibilities for further clinical trials of murepavadin in people with CF or non-CF bronchiectasis.

Reference

Spexis reports solid safety and pharmacokinetics results from first-in-human study with inhaled murepavadin, a novel macrocycle compound. News release. Spexis AG; January 9, 2023.