Asunercept

Asunercept (INN; development codes APG101 and CAN008)^[1] is a soluble CD95-Fc fusion protein which is in clinical development for the treatment of glioblastoma multiforme (GBM) and myelodysplastic syndromes (MDS).^[2] Asunercept has been granted orphan drug status for the treatment of GBM and MDS in the EU and the US.^[3][4][5] It has also received PRIME designation by the European Medicines Agency (EMA) for the treatment of GBM.^[6]

Asunercept

Legal status
Legal status	Investigational
Identifiers
CAS Number	1450882-18-4
DrugBank	DB15160
UNII	F333OQQ9UV

Mechanism of action

Asunercept blocks the CD95–ligand (CD95L) from binding to the CD95-receptor (CD95), which induces apoptosis. In oncology, this blockade is intended to prevent the killing of activated T cells^[7] that can be induced by tumor-associated macrophages (TAMs),^[8] endothelial cells,^[9] or fibroblasts.^[10]

In MDS, CD95L-signaling is a negative regulator of erythrocyte production in the bone marrow and its blockade has been shown to rescue erythroid progenitors.^[11]

Clinical development

A randomized, double-blind, placebo-controlled phase I study to examine the safety and tolerability of asunercept has shown that it is well tolerated.^[12] The efficacy of asunercept was tested in a phase II randomized controlled trial for patients with GBM. A total of 83 patients with first or second relapse of GBM were enrolled in the successful proof-of-concept trial. The primary goal of doubling the number of patients reaching progression-free survival at six months (PFS6) was substantially exceeded.^[13]

Asunercept has also been successfully tested in a phase I trial to treat patients with MDS.^[14] MDS is a disease in which the bone marrow does not make enough healthy blood cells, which leads to blood cytopenias, especially anemia.^[15]