New Treatment Receives Orphan Drug Designation for Treating Peripheral T-Cell Lymphoma

August 23, 2016

The FDA is granting Orphan Drug Designation for chimeric antigen receptor engineered T-cells directed against the target protein CD4 (CD4CAR) for the treatment of peripheral T-cell lymphoma.

Clinicians now have a new alternative to offer their patients with peripheral T-cell lymphoma (PTCL).  The US Food and Drug Administration (FDA) is granting Orphan Drug Designation for chimeric antigen receptor engineered T-cells (iCell Gene Therapeutics) directed against the target protein CD4 (CD4CAR) for the treatment of PTCL.

A chimeric antigen receptor (CAR) engineered T-cell is a patient's T-cell that has been genetically modified to express a protein on its surface with the capability to bind to a target protein on another cell. Upon binding to the targeted protein, the CAR protein will send a signal across the cell membrane to the interior of the T-cell to set in motion mechanisms to selectively kill the targeted cell.

CD4CAR is in development for CD4+ T-cell malignancies. The novel CD4-specific chimeric antigen receptor engineered T-cells are properly matched allogeneic human T-cells engineered to express an anti-CD4scFV antibody domain. An initial phase I clinical study is being planned through collaboration between iCell Gene Therapeutics, the National Institutes of Health, Indiana Clinical and Translational Sciences Institute, Stony Brook Hospital and the Blood and Marrow Transplantation Division, and the University of Louisville.

“We are very excited to have this opportunity to partner with iCell Gene Therapeutics to lead the efforts of preparing this cutting-edge immunotherapy into first-in-human clinical trial for patients suffering this extremely difficult-to-treat T-cell lymphoma,” said William Tse, MD, who is the chief of the Blood and Marrow Transplantation Division in the Department of Medicine at the University of Louisville School of Medicine, in a news release.  

The Orphan Drug Designation program provides a host of benefits, including orphan status and associated development incentives, to drugs and biologics for the treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people in the United States.

Researchers are hoping that this marks an important new era in the treatment in T-cell hematologic cancers. Currently, there are clinical development programs ongoing with CAR T-cells for CD19+ cell hematological malignancies. However, until now CD4+ PTCLs have not been targeted by a CAR therapy in a human trial. PTCLs account for 10% to 15% of all non-Hodgkin lymphomas (NHLs) and are more difficult to treat in comparison to B-cell NHLs.

With few exceptions, T-cell NHLs have poorer outcomes, lower response rates, shorter times to progression, and shorter median survival in comparison to B-cell NHLs. Subsequently, the standard of care for PTCLs is not well-established and the only potential curative regimen is bone marrow transplantation (BMT). However, BMT is often poorly tolerated and is not an option for a significant subset of patients with resistant disease.

Diseases covered by iCell Gene therapeutics’ proprietary CAR technologies include B- and T-cell lymphoma and leukemia, myeloproliferative neoplasms, myeloid dysplastic syndrome (MDS), acute myeloid leukemia (AML), multiple myeloma (MM), nonhematological (nonblood) cancers, and autoimmune disorders.