Spero Therapeutics Inc. (SPRO) has presented promising results from a Phase 1 trial, indicating substantial lung absorption of SPR719, with elevated concentrations in the epithelial lining fluid (ELF) and alveolar macrophages (AM). This outcome can be credited to the fact that penetration into lung compartments is predominantly driven by unbound plasma concentrations.
The trial aimed to evaluate the safety and intrapulmonary pharmacokinetics (PK) of SPR719, assessing its concentrations in ELF and AM within the lungs. This forms an essential part of informing the dosage strategy for developing SPR720 as a treatment for Non-Tuberculous Mycobacterial Pulmonary Disease (NTM-PD).
Conducted as a Phase 1, single-center, open-label study, the trial involved healthy adult participants of both genders. Each subject received a daily 1,000 mg dose of SPR720 for a duration of seven days. Blood samples were taken to evaluate plasma PK, and each participant underwent a standardized bronchoscopy and Bronchoalveolar Lavage (BAL) on the seventh day. The safety analysis included 33 subjects, while the PK analysis comprised 30 individuals.
The study observed no significant concentrations of SPR720 in plasma. The mean plasma levels of SPR719 reached their peak approximately four hours post-administration and gradually decreased throughout the subsequent 24-hour period.
Interestingly, the ELF and AM concentrations of SPR719 exceeded the total plasma concentrations.
These findings underscore SPR719's strong lung absorption and elevated ELF and AM concentrations, demonstrating that unbound plasma concentrations chiefly contribute to its penetration into lung compartments.
Furthermore, the trial did not reveal any unexpected safety concerns. Spero Therapeutics highlighted that the study’s outcomes positively reinforce the potential of SPR720 as an oral therapeutic agent for NTM-PD, warranting further exploration.
