Targeted Genetics Announces Promising Results for Cystic Fibrosis Gene Therapy

Strategic Insights -

Targeted Genetics Corporation has made significant strides in developing a gene therapy for cystic fibrosis (CF), with the company's proprietary vector, tgAAV-CFTR, demonstrating safe and effective gene transfer in a Phase I trial. The study, conducted at Stanford University's School of Medicine, involved 10 patients with CF, who received escalating doses of tgAAV-CFTR delivered directly to the maxillary sinus. The results showed that the patients at the highest dose level averaged one copy of the vector per cell, with long-term persistence of the CFTR gene for at least 70 days. The study's principal investigator, Phyllis Gardner, M.D., noted that the trial supported the use of the maxillary sinus as a surrogate for cystic fibrosis lung disease.

Key Takeaways:

  • The Phase I trial of tgAAV-CFTR demonstrated safe, dose-dependent, and effective gene transfer using the AAV-CFTR vector.
  • The study showed that tgAAV-CFTR was well tolerated and demonstrated no adverse effects or neutralizing immune response, even after repeat delivery.
  • Long-term persistence of the CFTR gene for at least 70 days was observed, exceeding that found historically using other types of vectors.
  • The results of the Phase I trial support the use of the maxillary sinus as a surrogate for cystic fibrosis lung disease.
  • A total of 10 patients were enrolled in the trial, with patients at the three highest dose levels showing evidence of gene transfer.
  • Targeted Genetics is currently completing a follow-up Phase II double-blinded, randomized, placebo-controlled study of tgAAV-CFTR.
  • The company plans to initiate Phase I trials of an aerosolized formulation of tgAAV-CFTR during the second half of 1998, which will provide widespread delivery to the airways of the human lung.

Statistics:

  • The Phase I trial involved 10 patients with CF, who received escalating doses of tgAAV-CFTR delivered directly to the maxillary sinus.
  • The patients at the highest dose level averaged one copy of the vector per cell.
  • Long-term persistence of the CFTR gene for at least 70 days was observed.
  • The study's principal investigator, Phyllis Gardner, M.D., stated that the results of the Phase I trial "demonstrated safe, dose-dependent, and effective gene transfer by means of the AAV-CFTR vector."
  • Targeted Genetics plans to initiate Phase II trials of tgAAV-CFTR in 1998.
  • The company's Phase II study will be a double-blinded, randomized, placebo-controlled study to test the safety and efficacy of tgAAV-CFTR in preventing sinusitis in patients with CF.

Sources:

  • "Efficient and Persistent Gene Transfer of AAV-CFTR in the CF Maxillary Sinus," The Lancet, June 6, 1998
  • Targeted Genetics Corporation press release, June 8, 1998
  • Statement by Phyllis Gardner, M.D., principal investigator, Stanford University's School of Medicine