pGM169 + GL67A

The drug pGM169 + GL67A is a gene therapy product developed for cystic fibrosis treatment. It consists of a combination of a plasmid DNA vector (pGM169) containing the CFTR gene and a cationic liposome (GL67A) that helps deliver the genetic material to cells in the respiratory tract. ## Composition and Mechanism pGM169 + GL67A works by delivering a functional copy of the CFTR gene to the cells lining the airways. The plasmid pGM169 contains a codon-optimized CFTR cDNA sequence coupled with a human elongation factor 1 alpha promoter (hCEFI) that provides longer duration of CFTR activity[5]. This plasmid was specifically designed to be completely devoid of CG dinucleotides, which have been associated with inflammatory responses in vivo[5][7]. The GL67A cationic lipid mixture forms small, tightly bound particles with the negatively charged plasmid DNA, creating complexes that can withstand aerosolization and be taken up by cell membranes in the respiratory tract[5]. Once inside the cells, the plasmid DNA is transported to the nucleus where it expresses the CFTR gene. ## Clinical Development The drug has undergone several clinical trials: 1. A Phase I/IIa pilot study evaluated safety, tolerability, and gene expression after a single dose of pGM169/GL67A administered to the nose and lungs of CF patients[6]. 2. A Phase IIb multi-dose clinical trial (completed in May 2014, ClinicalTrials.gov identifier: NCT01621867) involved CF patients receiving 12 monthly doses of pGM169/GL67A or placebo by aerosol[4]. This trial demonstrated a modest but significant improvement in lung function, with a 3.7% increase in predicted FEV1 and stabilization of lung function observed in the treatment group[9]. In the clinical trials, each 5 mL dose of pGM169/GL67A contained 13.3 mg of plasmid DNA and 75 mg of the GL67A lipid mixture[1]. The drug was administered via nebulization through a Trudell AeroEclipse II device[1]. This gene therapy approach offers proof of concept that non-viral gene therapy can benefit lung function in CF patients and creates opportunities for follow-up studies, potentially combining gene therapy with CFTR modulator drugs[9].

Other names

pGM169/GL67A