FDA Names Arcellx’s Cell Therapy CART-ddBCMA Orphan Drug for Multiple Myeloma

Arcellx’s CART-ddBCMA — a CAR T-cell therapy targeting the BCMA protein — was granted orphan drug status by the U.S. Food and Drug Administration (FDA) for the treatment of multiple myeloma.

The move follows the FDA’s granting of fast track designation to the therapy for relapsed or refractory myeloma, and provides the company with various incentives. Those include assistance in developing trial protocols and a seven-year period of market exclusivity once the treatment is approved.

The company is recruiting participants for a Phase 1 trial (NCT04155749) testing the therapy in relapsed and refractory multiple myeloma. The trial is the first evaluating the treatment in humans, and is being conducted at two U.S sites, in Chicago and Boston.

“Orphan designation recognizes the unmet need of populations with rare diseases like multiple myeloma, particularly for those patients who have exhausted other therapeutic options,” Amy B. Fix, senior vice president of regulatory affairs of Arcellx, said in a press release.

“Receiving both orphan and fast track designations further validates the potential of Arcellx technology and our novel binding domain,” Fix said. “We hope to provide patients with a new therapy that may significantly improve treatment response for this debilitating disease.”

CAR T-cell therapy harnesses a patient’s own immune cells to fight cancer. These therapies consist of collecting a patient’s T-cells — a type of immune cell with the ability to fight cancers — and genetically modifying them in the lab to produce a chimeric antigen receptor, or CAR, that targets a specific cancer protein.

While conventional CAR T-cells recognize a single cancer protein, Arcellx makes use of a proprietary platform — the ARC-T + sparX cell therapy platform — that allows CAR T-cells to bind multiple targets, potentially eliminating a broader population of cancer cells.

In fact, the binding domain of the CAR receptor does not bind directly to the cancer protein. Instead, it has a domain prepared to bind a universal “TAG” protein. Cells are then armed with a protein antigen-receptor X-linker (sparX), carrying one or more tumor-targeting binding sites, fused to the TAG.

According to the company, these modifications result in a therapy with more specificity to kill tumors. And, because the dose of sparX can be adjusted, it is possible to control the rate of tumor killing and the therapy’s toxicity.

Arcellyx is developing a pipeline of sparX proteins to direct the activity of ARC-T cells in several cancers. For multiple myeloma, the cells are armed with a sparX protein targeting the B-cell maturation antigen (BCMA).

“We are pleased to be one of the first sites to test this new technology in the clinic,” said Matthew Frigault, MD, assistant director of cellular therapy service at Massachusetts General Hospital Cancer Center and an instructor at Harvard Medical School.