On March 18, 2020, the U.S. Food and Drug Administration (FDA) granted an Orphan Drug Designation for ALPN-101 for the prevention and treatment of acute graft-versus-host disease (aGvHD).1
ALPN-101 is a first-in-class Fc fusion protein of a human inducible T-cell costimulator ligand (ICOSL) variant immunoglobulin domain (vIgD™). The drug targets inflammatory process by simultaneous inhibition of the CD28 and ICOS signaling pathways, which are involved in T-cell activation. Results in preclinical models of GvHD, and other autoimmune and inflammatory diseases, such as inflammatory arthritis, and multiple sclerosis, revealed improved efficacy of dual CD28-ICOS blockade with ALPN-101 vs single pathway blockade.2
A phase I study (NCT03748836) of ALPN-101 in healthy volunteers completed enrolment in October 2019. The initial data were presented at the American Society of Hematology annual meeting in December 2019, with more data expected in 2020. A phase I/IIb Balance study (NCT04227938) investigating ALPN-101 in patients with steroid-refractory/resistant aGvHD is currently recruiting.