Orchard Therapeutics Reports Clinical Proof-of-Concept Data for X-CGD Gene Therapy at ASH

Rare Daily Staff

Orchard Therapeutics said it presented the first demonstration that its experimental gene therapy OTL-102 for the treatment of X-Linked Chronic Granulomatous Disease (X-CGD) leads to sustained levels of functioning neutrophils after 12 months.

Donald Kohn, a member of Orchard’s scientific advisory board, presented the clinical proof-of-concept data from an ongoing academic clinical trial evaluating OTL-102 during the 2018 American Society of Hematology (ASH) Annual Meeting & Exposition.

X-CGD is a life-threatening inherited immunodeficiency disorder which is caused by a genetic mutation that results in the inability of neutrophils to effectively kill bacterial and fungal pathogens. This immune deficiency leads to repeated chronic and severe infections often requiring hospitalization and resulting in chronic sequelae leading to early mortality. Orchard licensed the gene therapy candidate from Genethon.

OTL-102 is an autologous ex vivo lentiviral gene therapy that utilizes a self-inactivating lentiviral vector.

The clinical proof-of-concept data are from seven patients (ages 2-27) severely affected by X-CGD treated with OTL-102. Six of the seven evaluable patients showed persistence of 16-46 percent (mean 30.2%) functioning neutrophils 12 or more months after treatment. Prior publicly available data suggests 10 percent is the minimum threshold necessary to show potential clinical benefit and restoration of both biochemical function and immunity.

Two additional patients were treated but died within three months of treatment from complications deemed by the investigator to be related to pre-existing disease-associated comorbidities due to advanced disease progression.

The company said these results are the first demonstration that ex vivo autologous hematopoietic stem cell gene therapy has the potential to produce sustained corrected neutrophil function for 12 months or more in severely affected X-CGD patients.

“X-CGD is a severe, life-threatening disease that leads to a significantly reduced quality and length of life in affected patients. Current treatment options, including prophylactic antibiotics, antifungals, and hematopoietic stem cell transplants, all have significant associated risk and limitations,” said Kohn. “By providing the first-ever demonstration that autologous hematopoietic stem cell gene therapy has the potential to lead to sustained levels of functioning neutrophils and thereby a long-term clinical benefit, we are hopeful that OTL-102 may provide a new treatment option for X-CGD patients to improve the quality and length of their lives, escaping the chronic infections and inflammation associated with the disease.”

December 7, 2018
Photo: Donald Kohn, a member of Orchard’s scientific advisory board