Orchard Therapeutics announced the U.S. FDA has granted Orphan Drug Designation for OTL-102, the company’s ex vivo autologous hematopoietic stem cell (HSC) gene therapy being investigated for the treatment of X-linked chronic granulomatous disease (X-CGD). The FDA may grant orphan designation to drugs and biologics intended to treat a rare disease or condition affecting fewer than 200,000 persons in the U.S.
Early academic clinical trial data for OTL-102 was recently published in Nature Medicine. The trial was led by researchers at the University of California, Los Angeles (UCLA) — including Donald B. Kohn, M.D., one of the study’s lead investigators and professor of microbiology, immunology and molecular genetics at UCLA — and Great Ormond Street Hospital (UK). The data provides an analysis of safety and efficacy outcomes in nine severely affected patients with X-CGD. At 12 months post-treatment, six of seven surviving patients, all of whom were adults or late adolescents, exceeded the minimum threshold hypothesized in published literature to demonstrate potential clinical benefit, defined as 10% functioning, oxidase-positive neutrophils in circulation and have discontinued preventive antibiotics.
As previously reported, two pediatric patients died within three months of treatment from complications deemed by the investigators and independent data and safety monitoring board to be related to pre-existing comorbidities due to advanced disease progression and unrelated to OTL-102. Investigators are planning to enroll additional pediatric patients in 2020 to assess outcomes in this patient population. In addition, there is work underway to improve the efficiency of the drug product manufacturing process prior to initiating a registrational study.
The studies are supported by multiple institutions including the California Institute of Regenerative Medicine, the Gene Therapy Resource Program from the National Heart, Lung, and Blood Institute, the National Institute of Allergy and Infectious Diseases Intramural Program, the Wellcome Trust and the National Institute for Health Research Biomedical Research Centres at Great Ormond Street Hospital for Children NHS Foundation Trust, University College London Hospitals NHS Foundation Trust and University College London.
X-linked chronic granulomatous disease (X-CGD) is a rare, life-threatening, inherited disease of the immune system caused by mutations in the cytochrome B-245 beta chain (CYBB) gene encoding the gp91phox subunit of phagocytic NADPH oxidase. Because of this genetic defect, phagocytes, or white blood cells, of X-CGD patients are unable to kill bacteria and fungi, leading to chronic, severe infections. The main clinical manifestations of X-CGD are pyoderma, a type of skin infection; pneumonia; colitis; lymphadenitis, an infection of the lymph nodes; brain, lung and liver abscesses; and osteomyelitis, an infection of the bone. Patients with X-CGD typically start to develop infections in the first decade of life, and an estimated 40 percent of patients die by the age of 35. The incidence of X-CGD is currently estimated at between 1 in 100,000 and 1 in 400,000 male births.
OTL-102 is an ex vivo autologous hematopoietic stem cell gene therapy. Preclinical and clinical development of OTL-102 had originally been initiated by Genethon (Evry, France) and funded by an EU framework 7 funded consortium, NET4CGD, before being licensed to Orchard.