Date: 2015-04-21
Type of information: Publication of results in a medical journal
phase: 1-2
Announcement: publication of results in the Journal of the American Medical Association (JAMA)
Company: Genethon (France) AFM-Telethon (France) UCL Institute of Child Health (UK) Great Ormond Street Hospital (UK) AP-HP (France) Inserm (France) Children's Hospital Boston (USA)
Product: autologous CD34+ cells transduced with a lentiviral vector containing the human Wiskott-Aldrich syndrome gene
Action
mechanism: gene therapy. This ex vivo gene therapy uses an HIV-derived lentiviral vector to transfer genes into autologous CD34+ hematopoietic stem cells from WAS patients.
Disease: Wiskott Aldrich syndrome
Therapeutic area: Rare diseases
Country: USA, UK, France
Trial
details: In total, this trial will involve fifteen patients, five for each site, who will be treated by 2013-2014. This WAS gene therapy trial is being run simultaneously in London, Paris and Boston to accelerate the testing of new advanced therapies for rare conditions (NCT01347242).
The trial ongoing at Necker-Enfants Malades in Paris is conducted by Marina Cavazzana-Calvo MD, Head of Clinical Investigation Center Biotherapy, Necker, Alain Fischer MD, Professor of Pediatric Immunology, Scientific Director of the Imagine Foundation and Salima Hacein-Bey Abina PhD, Professor of Immunology and Head of the Gene Therapy Laboratory (NCT02333760).
The Boston trial will be funded by the National Heart, Lung and Blood Institute (NHLBI) through its Gene Therapy Resource Program (GTRP). Principal investigators at Children’s are Sung-Yun Pai, MD, Division of Hematology/Oncology, and Luigi Notarangelo, MD, director, Research and Molecular Diagnosis Program on Primary Immunodeficiencies, Division of Immunology. David A. Williams, MD, chief of the Division of Hematology/Oncology and director of Translational Research for Children’s Hospital Boston, will serve as sponsor-investigator. The gene insertion of patient cells will be accomplished in the Connell O\'Reilly Family Good Manufacturing facility at the Dana-Farber Cancer Institute in collaboration with the Center for Human Cell Therapy at Harvard Medical School.
Latest
news: * On July 21, 2011, Genethon and Children\'s Hospital Boston have announced that the FDA has approved the launching in the U.S. of a clinical trial for gene therapy for Wiskott-Aldrich syndrome (WAS). After its implementation in Paris and London, this trial based on preclinical research performed at Genethon (Evry, France) which also manufactures the GMP gene therapy product, is now going to be launched in Boston. It’s one of the first international clinical trials using a gene therapy treatment for a rare disease.* On April 21, 2015, french teams from CIC Biothérapie (AP-HP/Inserm), from pediatric hematology department of Necker Hospital for Children (AP-HP), led by Marina Cavazzana, Salima Hacein Bey Albina and Alain Fischer and from Genethon led by Anne Galy (Genethon/Inserm UMR-S951), and English teams from UCL Institute of Child Health and Great Ormond Street Hospital in London led by Adrian Thrasher and Bobby Gaspar demonstrated the efficacy of gene therapy treatment for Wiskott-Aldrich
Syndrome (WAS). Six children that were treated and followed for at least 9 months had their immune system restored and clinical condition improved. This work was published in the Journal of the American Medical Association (JAMA), and carried out with support from the AFM-Telethon.
The Phase I / II study, with Genethon as the promoter, was launched in December 2010 and conducted in Paris and London to treat severely ill patients without a compatible donor. This study, which is ongoing, assesses the feasibility and efficacy of gene therapy in this indication. The article published in JAMA reports the results for the first six patients, aged 8 months to 16 years, where the monitoring period allowed assessment of the initial effects of the treatment. The treatment involves collected blood stem cells carrying the genetic anomaly of patients and corrected them in the laboratory by introducing a healthy WAS gene using a lentiviral vector developed and produced by Genethon. The corrected cells were reinjected into patients who in parallel were treated with chemotherapy to suppress their defective stem cells and autoimmune cells to make room for new corrected cells. After reinjection, these cells were then differentiated into the various cell lines that make up the blood (red and white cells,
platelets).
To date treated patients showed significant clinical improvement. Severe eczema and severe infection disappeared in all cases. Arthritis was eliminated in one patient and another saw major improvement in vasculitis of the lower limbs and was able to return to normal physical activity without a wheelchair. However, the rate of corrected platelets varies from one patient to another.
Ref: Outcome following Gene Therapy in Patients with Severe Wiskott-Aldrich Syndrome. Salima Hacein-Bey Abina et al. JAMA. 2015;313(15):1550-1563. doi:10.1001/jama.2015.3253.
Earlier this year, Généthon and Children\'s Hospital Boston announced that they have initiated a partnership to conduct a gene therapy clinical trial for this severe immunodeficiency disease. Genethon is sponsoring parallel trials at Great Ormond Street Hospital in London and Hopital Necker-Enfants Malades in Paris and is supplying the vector for all clinical sites. This clinical trial results from a research program initiated in 2002 by the group of Anne Galy at Genethon (Inserm UMR951/Généthon, Université d\'Evry Val d\'Essonne, EPHE), which has developed this ex vivo approach.
Généthon is sponsoring parallel trials at Great Ormond Street Hospital in London and Hopital Necker-Enfants Malades in Paris and will be supplying the vector for the trial at the US site. The vector is manufactured by Généthon in Evry. Altogether, the WAS gene therapy trials in London, Paris and Boston will constitute a unique multicenter collaboration to accelerate the testing of new advanced therapies for rare conditions.
