Novel CF Gene Therapy from UKCFGTC and VGXI Improves FEV1 in Clinical Trial

Gene therapy in the context of treating cystic fibrosis made a significant step forward with the announcement of positive data from a Phase IIb clinical trial investigating the VGXI-manufactured aerosolized DNA plasmid expressing Cystic Fibrosis Transmembrane Conductance Receptor (CFTR) — an experimental CF therapy that improved a key lung function measurement in cystic fibrosis patients. The trial was a result of a collaboration between the United Kingdom Cystic Fibrosis Gene Therapy Consortium (UKCFGTC) and VGXI that has lasted for more than ten years.

“One hundred and thirty-six patients aged 12 and above received monthly, inhaled doses of the gene therapy or a placebo for one year,” said Professor Deborah Gill, of Oxford University, in a news release. “The results are encouraging and are expected to lead to a further study to assess higher, more frequent doses.”

Before this trial, VGXI and the UKCFGTC worked together to enable pre-clinical studies to feed into the clinical trial program. In this Phase IIb clinical trial, 140 patients who had cystic fibrosis as a result of any combination of mutations in the CFTR gene were randomized to receive either nebulized non-viral gene therapy or placebo. All patients were evaluated for forced expiratory volume in one second (FEV1) percent predicted at baseline and after one year of treatment. Treatment consisted of either nebulized pGM169/FL67A gene liposome complexes or saline, based on the treatment arm designation.

At the end of the trial, patients receiving the gene therapy demonstrated a modest but noteworthy improvement in FEV1 compared to the patients receiving placebo. As explained by the published results appearing in The Lancet, entitled “Repeated Nebulisation of Non-Viral CFTR Gene Therapy in Patients with Cystic Fibrosis: A Randomised, Double-Blind, Placebo-Controlled, Phase 2b Trial,” the improvement in “FEV1 percent predicted” indicated a stabilization of lung function. There were no significant differences in adverse events related to treatment, which was given every 28 days.

The collaboration between VGXI and the UKCFGTC began in 2005, at which time they entered a multi-year supply agreement to produce the CFTR plasmid at VGXI’s cGMP production facility. “We are delighted that the UKCFGTC has continued to trust in VGXI’s manufacturing capabilities,” said Young Park, President and CEO of VGXI. “The entire VGXI team is committed to providing the highest quality DNA products and services, and it is rewarding to see these products make a meaningful impact on patients’ quality of life.”

With the conclusion of this trial, VGXI and the UKCFGTC intend to increase the functionality of the gene therapy to see if a more significant difference in FEV1 percent predicted can be identified in the next clinical trial.