美国FDA已审批应用干细胞化妆品.pdf

Clinical Review BLA 125348 1. EXECUTIVE SUMMARY 1.1 Brief Overview of Clinical Program Isolagen Therapy (IT) is acellular product consisting of autologous fibroblasts developed for the treatment of moderate to severe nasolabial fold wrinkles for up to six months in adults. The fibroblasts are derived from patients’ post-auricular skin biopsies, expanded in culture, and suspended in proprietaryisotonic medium. The final cell suspension is injected intradermally into patients’ nasolabial folds. The treatment regimen comprises three sets of injections with a five-week interval between injections. IT is injected intradermally into the nasolabial fold wrinkles at the doseof 0.1 mL per linear cm, up to a total dose of 2 mL per treatment. The product has gone through three Phase 2 and four Phase 3 studies under IND. The BLA application was submitted on March 6, 2009. The application included study reports of seven clinical trials. Of these seven trials, the Phase 3 studies IT-R-005 and IT-R-006 were conducted under US Food and Drug Administration (FDA) Special Protocol Assessment (SPA) agreements. Studies IT-R-005 and IT-R-006 were conducted at 13 study centers (seven in 005 and six in 006) in the U.S. from October 23, 2006 to June 26, 2008. The other five clinical studies varied in the injection sites, the cell doses and injection volumes, the interval between sets of injections, and study duration. Mechanism of action of IT was not examined in human or animal studies. The data supporting efficacy claims were derived from the two trials, IT-R-005 and IT-R- 006 (combined, n=421, 210 IT and 211 vehicle-control). Efficacy data from the other five trials were also reviewed. Conducted under an identical protocol, Studies IT-R-005 and IT-R-006 were multiple center, randomized,double-blind, vehicle-controlled trials to assess the efficacy and safety of IT. In these studies, the control subjects received injections of vehicle medium (proprietary iso