Phase 1 trial to begin of CAR T-cell therapy azer-cel for progressive MS
Formerly PBCAR0191, azer-cel is designed to target and eliminate B-cells
TG Therapeutics plans to soon launch a Phase 1 clinical trial to investigate the CAR T-cell therapy azercabtagene zapreleucel, or azer-cel, in people with progressive forms of multiple sclerosis (MS).
The announcement comes after the U.S. Food and Drug Administration (FDA) cleared TG’s investigational new drug (IND) application, allowing it to begin clinical trials of azar-cel with people.
Azer-cel was originated by Precision Biosciences, but TG Therapeutics acquired the global rights in January to develop it for autoimmune diseases and other indications outside cancer. The licensing deal gave Precision an upfront payment of $17.5 million and the company is also eligible to receive milestones payments of up to $288 million.
“We would like to congratulate TG Therapeutics on receiving IND clearance for azer-cel in patients with progressive multiple sclerosis,” Michael Amoroso, CEO of Precision BioSciences, said in a press release. “We believe the expansion of allogeneic CAR T into autoimmune diseases holds the potential to unlock new therapies for patients living with chronic disease.”
MS is an autoimmune disease where the immune system erroneously attacks the brain and spinal cord, causing inflammation and nerve cell damage. B-cells, a type of immune cell that produces antibodies, are one of the main drivers of this inflammatory attack. Eliminating the cells is a therapeutic strategy used by several MS disease-modifying therapies that have shown promise in relapsing forms of MS. Only Ocrevus (ocrelizumab), an antibody that targets B-cells by binding to the CD20 protein at their surface, is approved for primary progressive MS, however.
Azer-cel targets B-cells using donor T-cells
Azer-cel, formerly PBCAR0191, is also designed to target and eliminate B-cells. It belongs to a class of allogeneic CAR T-cell therapies where a donor’s immune T-cells are modified with a man-made receptor to target and eliminate other cells. T-cells can recognize specific molecules on the surface of cells. Once they do, one function is to kill the flagged cells in a highly specific manner.
But T-cells can be engineered to become more effective and specific. This is done by loading them with a chimeric antigen receptor (CAR) designed to recognize a particular target.
Azer-cel contains CAR T-cells that are modified to recognize CD19, a molecule on the surface of B-cells. Once infused into the patient, the modified T-cells should eliminate these cells from circulation.
Most CAR-T cell therapies are made with a patient’s own T-cells, which avoids complications from donor-derived cells. But as an allogeneic CAR T-cell therapy, azer-cel uses T-cells from a donor to create an “off the shelf” option to make the treatment more accessible.
While this could give rise to complications such as graft-versus-host disease (GVHD), wherein the donor T-cells attack the patient’s healthy cells and tissues, Precision Biosciences’ designed azer-cel to mitigate these complications. The company has already tested the therapy in a number of B-cell cancers and the results have been generally positive.
“We look forward to TG Therapeutics initiating a clinical trial for azer-cel in autoimmune disease as we focus on the advancement of our own wholly owned in vivo gene editing pipeline,” Amoroso said.
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