ARU-1801 Gene Therapy Granted Orphan Drug Status in EU

The European Medicines Agency (EMA) has granted the designation of orphan drug to ARU-1801, an experimental gene therapy being developed by Aruvant, for the treatment of sickle cell disease (SCD).

The decision, based on a positive recommendation by the EMA’s Committee for Medicinal Products for Human Use, will provide incentives to the company to further develop the treatment, including fee waives, trial protocol assistance, and 10 years of marketing exclusivity upon approval.

“The EMA orphan designation highlights the importance of ARU-1801, our potentially curative gene therapy for individuals living with severe SCD,” Will Chou, MD, CEO of Aruvant, said in a press release.

Orphan designation is given to investigative therapies with the potential to be safe and effective for rare, life-threatening, or chronically debilitating conditions that have no approved treatments, or where the potential therapy is showing significant benefit over existing treatments.

ARU-1801 uses a proprietary technology that is intended to increase the number of functional red blood cells. It does so by inserting a modified version of the HBG gene directly into the patients’ own stem cells.

The modified gene, which is inserted in cells via a special viral vector called a lentivirus, provides the instructions for a protein called fetal hemoglobin — a form of hemoglobin produced during fetal development that is more effective at transporting oxygen than its adult counterpart.

By increasing fetal hemoglobin levels, ARU-1801 is expected to restore red blood cell function and improve oxygen transport throughout the body, alleviating disease symptoms.

The gene therapy is being tested as a one-time treatment for SCD in an open-label Phase 1/2 clinical trial (NCT02186418). Called MOMENTUM, the trial is recruiting 10 adults, age 18 to 45, across sites in the U.S., Canada, and Jamaica. More information can be found here.

During the trial, blood stem cells will be harvested from patients’ bone marrow, treated with ARU-1801, and then reintroduced into circulation. Prior to infusion, however, patients undergo a reduced-intensity conditioning (RIC) regimen to eliminate the “defective” blood-forming stem cells and prepare them for the introduction of the genetically modified cells.

RIC is a conditioning regimen that involves low-intensity chemotherapy and/or radiotherapy. It is associated with fewer and less severe side effects than other high-intensity conditioning regimens.

If successful, patients will be evaluated for up to 15 years after receiving the treatment. The goal is to assess whether a single treatment is sufficient over a lifetime, or, if not, how frequently patients need to be treated.

“We are encouraged by the preliminary clinical data from our ongoing Phase 1/2 study that demonstrates ARU-1801, administered with only reduced intensity conditioning, can achieve durable reductions in disease burden,” Chou said.

The therapy has also received orphan drug and rare pediatric disease designations from the U.S. Food and Drug Administration as a potential SCD treatment.