ARU-1801 (Aruvant), Investigational Gene Therapy for Treatment of Sickle Cell Disease: Regulatory Update

ARU-1801 (Aruvant), Investigational Gene Therapy for Treatment of  Sickle Cell Disease: Regulatory Update

Highlights of ARU-1801 Program:

- Sickle Cell Disease is an inherited disorder that affects the production of hemoglobin
- ARU-1801 is an investigational gene therapy developed by Aruvant Therapeutics
- ARU-1801 received orphan designation by FDA & EMA
- Company announced that the results from the phase 1/2 study (MOMENTUM) will be presented in ASH 2020 (December)

Sickle cell disease affects 100,000 individuals in the United States, disproportionately affecting African Americans with one in 500 African Americans suffering from the disease. This inherited disease affects the production of hemoglobin, a protein in red blood cells that carries oxygen throughout the body. The disease occurs when people inherit a mutation from each of their parents which causes people with SCD to not have normal, healthy adult hemoglobin in their red blood cells and instead have an abnormal hemoglobin called sickle hemoglobin. 
SCD can cause frequent episodes of severe pain, weakness and other serious complications. Fetal hemoglobin is an “anti-sickling” hemoglobin that is present before birth in the red blood cells. After birth, the gene that makes fetal hemoglobin turns off, which mostly stops the production of fetal hemoglobin. More fetal hemoglobin in the blood can mean fewer episodes of sickling and pain.

ARU-1801 is a one-time potentially curative investigational gene therapy for individuals living with sickle cell disease. This product candidate was designed to address the limitations of current treatment options including myeloablative chemotherapy toxicity, donor availability, and chronic administration, and replace it with a curative therapy. ARU-1801 incorporates a patented modified gamma-globin into autologous stem cells, with the aim of restoring normal red blood cell function through increased levels of fetal hemoglobin. The high potency of the modified gamma-globin enables ARU-1801 engraftment with only reduced intensity conditioning (RIC).

Regulatory Status 

U.S. Food and Drug Administration (FDA) 
FDAgranted Orphan Drug and Rare Pediatric Disease Designations to ARU-1801 for the treatment of sickle cell disease (SCD).

European Medicines Agency (EMA) 
EMA has granted orphan designation for ARU-1801

Clinical Study Update (MOMENTUMS)

Data presented at ASH is from the MOMENTUM study, an open label Phase 1/2 clinical trial examining ARU-1801 as a one-time potentially curative gene therapy for individuals with sickle cell disease (SCD). The MOMENTUM study, which continues to enroll patients, examines ARU-1801, an autologous cell therapy leveraging a modified gamma globin lentivirus vector, in individuals with severe SCD. 
Unlike investigational gene therapies that require fully myeloablative conditioning, ARU-1801 is given with reduced intensity conditioning (RIC), which is a lower dose chemotherapy. ARU-1801 is designed to address the limitations of current curative treatment options, such as low donor availability and the risk of Graft-versus-Host Disease (GvHD) seen with allogeneic stem cell transplants. The data to be presented at ASH highlights participants dosed with product manufactured with both the original academic manufacturing process and the enhanced Process II.