Asunercept

APG101 is a soluble CD95-Fc fusion protein currently under development for the treatment of Glioblastoma multiforme (GBM) and myelodysplastic syndromes (MDS). This compound acts by blocking the CD95–ligand (CD95L) from binding to the CD95-receptor (CD95), thereby disrupting a key mechanism in tumor cell growth and migration.

Overview

APG101 offers an innovative approach to addressing the treatment of GBM, aiming to extend both progression-free survival and overall survival rates for patients afflicted with this aggressive brain tumor. The therapeutic approach is grounded in research from the German Cancer Research Center (DKFZ).

Clinical Trials

Phase I

A randomized, double-blind, placebo-controlled phase I study examining the safety and tolerability of APG101 concluded that the compound was well-tolerated by participants.

Phase II

The efficacy of APG101 was rigorously tested in a randomized controlled phase II trial involving patients diagnosed with GBM. Initiated in late 2009, the initial results from this study emerged in 2012. 83 patients, either experiencing their first or second relapse of GBM, were enrolled in this successful trial. Notably, the primary objective - which was to double the number of patients reaching progression-free survival at six months (PFS6) - was significantly surpassed.

Mechanism of Action

Research, such as that by Kleber et al., has illuminated the role of the CD95 ligand in stimulating the invasive growth of glioblastoma cells. Consequently, by inhibiting the interaction of the CD95 ligand with its receptor using APG101, the growth and migration of tumor cells can be effectively reduced. Supporting evidence for the therapeutic potential of APG101 in tumor treatment is provided in a publication in the renowned scientific journal, Nature, by Prof. Marcus Peter and his team from the University of Chicago.

Current Development

APG101 is currently undergoing a phase I trial for the treatment of MDS, a condition where the bone marrow fails to produce sufficient healthy blood cells, leading to conditions such as anemia.

Designations

For its potential role in treating GBM, APG101 has been awarded orphan drug status both in the EU and the US. Additionally, for its prospective use in treating MDS, it has been given orphan drug designation in the US.

Summary

Asunercept is a human soluble fusion protein consisting of the extracellular domain of the CD95 receptor fused to the Fc-domain of the human IgG antibody, with potential antineoplastic activity. Upon administration, asunercept binds to the CD95 ligand (CD95L) and blocks the binding of CD95L to the CD95 receptor. In tumor cells, blockage of CD95L-mediated signaling pathways may prevent cell migration and invasive cell growth; in healthy cells, blockage of CD95L-mediated signaling pathways may prevent apoptosis and may protect cell damage. Activation of the CD95 receptor plays an important role in the initiation of apoptosis in healthy cells or the invasive growth of cancer cells.

See Also

• Glioblastoma multiforme
• Myelodysplastic syndrome
• Orphan drug

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