Rocket Pharmaceuticals has started treatment with its investigational gene therapy, RP-L201, in a Phase I/II clinical trial to treat severe Leukocyte Adhesion Deficiency-I (LAD-I).

RP-L201 is a lentiviral vector (LVV)-based therapy that contains autologous genetically modified CD34+ hematopoietic cells. Rocket licensed the product from the Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT) in Spain.

LAD-I is a rare disorder caused by a mutation of the ITGB2 gene. The paediatric disease can lead to fatal infections as white blood cells lose the ability to leave the bloodstream to fight the infection.

Without a successful bone marrow transplant, severe LAD-I is associated with 60-75% mortality in the initial two years of life and survival beyond five years is rare.

The non-randomised, open-label Phase I/II study is designed to assess RP-L201 for the treatment of severe LAD-I in nine paediatric patients worldwide.

“Our hope is that patients would benefit from a one-time administration of autologous gene therapy.”

Phase I of the study will investigate the gene therapy’s safety and tolerability, while the Phase II portion will monitor the participants’ overall survival.

The survival will be established by the proportion of patients alive at the age of two and a minimum of one-year after infusion without allogeneic hematopoietic stem cell transplant (HSCT).

In addition, the Phase II portion will characterise the safety and toxicity of the RP-L201 infusion.

Rocket Pharmaceuticals CEO and president Gaurav Shah said: “LAD-I represents a major area of unmet medical need as most severely-afflicted patients die before the age of two in the absence of a hematopoietic stem cell transplant, which is associated with graft-versus-host disease.

“Our hope is that patients would benefit from a one-time administration of autologous gene therapy facilitated with busulfan conditioning. This process does not require immunosuppression and eliminates the risk of graft-versus-host disease.”

The company expects to complete the Phase I/II trial in 2023.