General AML

The FDA grants MGD006 Orphan Drug Designation for AML

On 5th January 2017, the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation for MGD006 for the treatment of Acute Myeloid Leukemia (AML).

CD123, the Interleukin 3 α-chain receptor (IL3RA), is differentially and significantly over expressed in majority of patients with AML. Binding of Interleukin 3 (IL-3) to CD123 can induce hematopoietic progenitor cell differentiation, proliferation and also upregulation of anti-apoptotic proteins. Additionally, CD123 has been identified as a marker for Leukemic Stem Cells (LSCs) (Al-Hussaini et al., 2016), which are a small population of stem cells that have properties of differentiation, self-renewal and homeostatic control and they contribute to the maintenance and propagation of AML. In AML, LSC reservoir can lead to disease resistance, relapse and often death in patients (Pollyea et al., 2014).

MGD006 is a Dual- Affinity Retargeting (DART) protein that was generated from antibodies to CD3 and CD123. MGD006 acts to redirect T- cells via CD3 to target AML blasts cells expressing CD123. This interaction can mediate, target-effector cell association, T- cell activation, proliferation and receptor diversification (Al-Hussaini et al., 2016).

Currently, MGD006 is being explored in a phase 1 dose-escalation study (NCT02152956), which is aiming to assess the safety and tolerability of this agent in relapsed and refractory AML patients.

  1. GlobeNewswire. MacroGenics’ MGD006 Granted Orphan Drug Status for AML by FDA. [Accessed 2017 Jan 26].
  2. Al-Hussaini M. et al. Targeting CD123 in acute myeloid leukemia using a T-cell–directed dual-affinity retargeting platform. Blood. 2016 Jan 7: 127(1): 122-131. DOI: 10.1182/blood-2014-05-575704. Epub 2015 Nov 3.
  3. Pollyea D A. et al. Targeting acute myeloid leukemia stem cells: a review and principles for the development of clinical trials. Haematologica. 2014 Aug; 99(8): 1277-1284. DOI: 10.3324/haematol.2013.085209.
Download this article:

You can now download this article in Adobe PDF® format.

Download as PDF