In short
Autologous CD34+ cells transduced with a lentiviral vector encoding the human NCF1 gene is an investigational gene therapy being studied for chronic granulomatous disease (CGD) caused by p47phox deficiency. The therapy, also known as SGX-001, is currently in a Phase 1/2 clinical trial with 5 planned participants. It has received orphan designation from the European Medicines Agency for this rare inherited immune disorder.
Key points
- Phase 1/2 trial authorised for p47-CGD, planning to enrol 5 participants.
- Gene therapy using the patient's own CD34+ blood stem cells modified with a lentiviral vector.
- Primary goal is safety, with a key efficacy measure being NADPH oxidase activity in at least 10% of granulocytes at Month 12.
- Orphan designation granted for this rare congenital immune disorder.
- Given as a single infusion after myeloablative conditioning.
What is autologous CD34+ cells transduced with a lentiviral vector encoding the human NCF1 gene?
Autologous CD34+ cells transduced with a lentiviral vector encoding the human NCF1 gene is an investigational gene therapy made from a patient's own blood stem cells. The cells are collected from the patient, modified in a laboratory using a lentiviral vector to carry a working copy of the NCF1 gene, and then returned to the patient. The product is also known by its development name SGX-001.
The substance is classified as a cell therapy of structurally diverse origin. It has no marketing authorisation in the product records, meaning it is not yet approved as a medicine. It has been granted orphan designation by the European Medicines Agency, a status for medicines targeting rare diseases. The product is supplied by Somagenetix AG.
How does it work?
Chronic granulomatous disease caused by p47phox deficiency is an inherited condition in which immune cells called phagocytes cannot produce the reactive oxygen compounds needed to kill certain bacteria and fungi. The NCF1 gene provides instructions for making the p47phox protein, a key part of the NADPH oxidase enzyme complex. In p47-CGD, mutations in NCF1 mean this complex does not work.
The therapy works by taking the patient's own CD34+ haematopoietic stem and progenitor cells and inserting a functional copy of the NCF1 gene into them using a lentiviral vector. When these modified cells are infused back, they are intended to develop into working phagocytes that can produce NADPH oxidase activity, restoring the immune system's ability to fight infections.
Which conditions is it used or studied for?
- Chronic granulomatous disease (CGD) caused by p47phox deficiency (p47-CGD) — an inherited immune disorder in which phagocytes cannot kill certain pathogens, leading to recurrent and severe infections and inflammatory complications. This is the only condition currently being studied for this therapy.
How is it given?
The therapy is prepared as a dispersion for infusion and is given by intravenous infusion. In the clinical trial, a single administration is given after myeloablative conditioning, a preparatory treatment that clears space in the bone marrow for the modified stem cells to engraft.
What do the clinical trials show?
One clinical trial is registered for this therapy. The trial, with EU CT number 2025-524423-50-00, is a Phase 1/2 study in patients with p47-CGD. It is currently authorised and plans to enrol 5 participants.
The primary outcomes focus on safety, including treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESIs), laboratory assessments, vital signs, ECGs and physical examinations, measured until Month 12. The key efficacy measure is the proportion of participants with NADPH oxidase activity in at least 10% of peripheral blood granulocytes at Month 12, indicating that the gene therapy has restored some immune cell function.
What side effects are known?
The registered trial is designed to evaluate side effects, but no side effect data are yet available from the sources provided. The trial records list safety endpoints including treatment-emergent adverse events and serious adverse events as the primary focus of the study.