Autologous hematopoietic stem cell gene therapy! The US FDA grants otl-102 orphan drug qualification to treat X-linked chronic granulomatosis (X-CGD)!

January 29, 2020 / BIOON / -- orchard therapeutics is a new gene therapy company in the UK, which is committed to changing the lives of patients with severe and life-threatening rare diseases through innovative gene therapy Recently, the company announced that the U.S Food and Drug Administration (FDA) has granted otl-102 the orphan drug qualification (odd) for the treatment of X-linked chronic granulomatosis (X-CGD) Otl-102 is a gene therapy of hematopoietic stem cells (HSC) in vitro prepared by self inactivated lentivirus vector (g1xcgd), which is currently being developed for the treatment of X-CGD X-CGD is a rare and life-threatening primary immunodeficiency, which is caused by mutation of cybb gene, which encodes gp91phox protein Otl-102 carries a codon optimized cybb complementary DNA fragment, which transduces autologous hematopoietic stem cells in vitro, and then transports them back to patients to express functional gp91phox protein Orphan drug (Orphan Drug) is a kind of medicine used for prevention, treatment and diagnosis of rare diseases Rare diseases are a general term for diseases with very low incidence rate, also known as orphan diseases In the United States, rare diseases refer to the types of diseases with a population of less than 200000 Incentives for drug research and development of rare diseases include various incentives for clinical development, such as tax credits related to clinical trial costs, FDA user fee relief, FDA assistance in clinical trial design, and a 7-year market monopoly period for the approved indications after the drug is launched Dr Anne dupraz poiseau, chief regulatory officer of orchard, said: "we are pleased to have obtained the orphan drug qualification from FDA, which shows that the agency recognizes the potential of otl-102 in the treatment of X-CGD patients X-CGD is a rare and life-threatening disease, which has significant unmet medical needs We are encouraged by the clinical data published so far and are eager to promote the research and development of otl-102 for X-CGD patients as soon as possible " X-CGD is a rare and life-threatening primary immune deficiency caused by mutation of cybb gene, which encodes gp91phox protein, which is an important part of NADPH oxidase complex, is a respiratory burst that produces superoxide and effectively kills ingested microorganisms Burst refers to the process that when neutrophils are activated, oxygen consumption is significantly increased, and most of the oxygen absorbed is required by the action of NADPH and NADH oxidase in cells to produce a large number of free radicals Due to the mutation of cybb gene, specific leukocytes, including neutrophils, can not effectively remove bacteria and fungi X-CGD patients are susceptible to severe chronic bacterial and fungal infections In addition, X-CGD can cause inflammation, which is characterized by granuloma formation and may endanger vital organs including the gastrointestinal tract and lungs Repeated infection and inflammation can seriously reduce the life expectancy of patients Prophylactic antibiotics and antifungal drugs can not prevent the progress of the disease At present, the only cure method, allogeneic hematopoietic stem cell transplantation, may be related to the toxicity related to graft-versus-host disease and the chemotherapy conditions required for allogeneic cell transplantation According to the data of otl-102 early academic clinical trials recently published in the international top journal of natural medicine (Article Title: lentivinal gene therapy for X-linked chronic granulomatous disease), this in vitro HSC gene therapy may be a promising method for the treatment of X-CGD This paper analyzed the safety and efficacy of otl-102 in 9 patients with severe infection of X-CGD The results showed that in the 12th month after treatment, 6 of the 7 survivors (both adults and late adolescents) showed persistent and stable oxidase positive neutrophils, which accounted for 16% - 46% of the circulating system in these patients, which exceeded the minimum threshold assumed in the published literature to show clinical benefits, defined as: function in the circulating system The proportion of sex oxidase neutrophils was 10% and prophylactic antibiotics had been stopped As mentioned earlier, two pediatric patients who died of complications within three months after treatment were associated with preexisting complications due to advanced disease progression, not otl-102, according to the study investigator and independent data and safety monitoring committee assessment Researchers plan to recruit more paediatric patients in 2020 to assess results in these patient groups In addition, orchard is working to improve the efficiency of the drug production process before the start of the registration study Adrian thrasher, one of the lead investigators of the study and professor of immunology at the Institute of child health, University College London, UK, said: "patients with X-CGD experience significantly reduced quality of life and life span, and currently must take drugs daily that do not eliminate the risk of fatal infection These data indicate that with the increase of follow-up time and patients, otl-102 may become a revolutionary new treatment option for patients with X-CGD " Dr Donald B Kohn, the first author and professor of pediatric hematology / oncology at the University of California, USA, previously said: "X-CGD is a serious threat, which can lead to a significant reduction in patients' quality of life and life span The current treatment options, including prophylactic antibiotics, antifungal drugs and hematopoietic stem cell transplantation, have significant risks and limitations We hope that otl-102 can provide a new treatment option for patients with X-CGD, improve the quality and length of life, and avoid chronic infection and inflammation related to diseases Original source: Orchard therapeutics announcements FDA granted orphan drug design for otl-102 for the treatment of X-linked chronic granular disease (X-CGD)