Ensoma launches clinical trial to prepare for CGD gene therapy

Biotechnology company Ensoma is recruiting participants for a clinical trial to help the company develop a gene therapy treatment for chronic granulomatous disease (CGD). Ensoma wants to measure adenovirus antibody levels and inflammatory markers, or cytokines, in both pediatric and adult male and female patients with CGD.

Adenoviruses are common and cause cold and flu-like infections. Ensoma is interested in adenovirus antibody levels because researchers are using a helper-dependent adenovirus, stripped of its viral genes, as a delivery system for the gene therapy.

Ensoma is developing in vivo, as opposed to ex vivo, gene therapy, a curative treatment that modifies genes and is still in clinical trials for various types of primary immunodeficiency (PI). In ex vivo gene therapy, clinicians remove stem cells from a patient, correct the genes in the cells, and administer the cells back to the patient. In in vivo gene therapy, the patient receives the viral packaged therapy directly and the viral vector modifies the cells inside the patient’s body.

“We know that patients may have been exposed to adenoviruses over the course of their lifetimes and if they have mounted a response to the adenovirus, the response can be measured by these antibodies. One of the concerns for the future might be whether those antibodies would interfere with the way the gene therapy works, so it’s a helpful thing to understand that in a patient population before you begin the gene therapy trial itself,” said Dr. Drew Dietz, Ensoma vice-president of clinical development.

Dietz said the purpose of testing both the antibodies and the cytokines is to increase the available scientific studies.

“As we get towards the actual gene therapy clinical trial itself, some of this information will help inform us about what we might want to do in the clinical trial. There is missing information, and this is part of trying to fill in the gaps,” said Dietz.

“Patients with chronic granulomatous disease have inflammation inside of their bodies to begin with and some of the cytokines involved in that inflammation are well-described but there are other cytokines that haven’t been looked at quite as much.

“While we are doing this profile of antibodies in patients with CGD, it seemed like a great opportunity to also take a look a little more deeply at a whole panel of the cytokines to see if we can confirm what the literature has talked about in terms of elevated cytokines in patients with CGD, to see if there is anything unique about their profiles.”

Ensoma’s gene therapy targets X-linked CGD patients only; six different genetic variations cause CGD and the X-linked type, which affects the CYBB gene, is the most common. Regardless of the gene affected, all people with CGD have neutrophils that don’t produce enough superoxide and hydrogen peroxide, important infection-fighting chemicals.

Dietz said the more knowledge Ensoma can gather about people with CGD, the better informed the researchers will be in developing the gene therapy treatment. If brought to market, gene therapy treatment in vivo for blood stem cells will be novel. To date, the only gene therapies targeting blood stem cells that have been approved are ex vivo, said Dietz.

“The goal of CGD in vivo gene therapies is very similar to that of bone marrow transplant: Get the patients normal functioning neutrophils that will allow them to fight infections, stop them from having complications from infections, and restore some of the balance of the immune system,” said Dietz.