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FDA grants orphan drug designation to iadademstat

Feb 16, 2021

On February 11, 2021, the U.S. Food and Drug Administration (FDA) granted orphan drug designation to iadademstat for the treatment of acute myeloid leukemia (AML).1


Iadademstat is an orally available, investigational, lysine-specific histone demethylase 1 (LSD1) inhibitor, which binds covalently to the flavin adenine dinucleotide (FAD) within the active site of LSD1.2

LSD1 is a chromatin remodeling enzyme responsible for the epigenetic regulation of a number of transcription factors involved in leukemia progression. Inhibition of LSD1 has demonstrated a potent differentiating effect in hematological cancers.1

Clinical status

The first-in-human phase I/IIa study investigating iadademstat in patients with relapsed or refractory AML showed that iadademstat monotherapy has a good safety profile and both clinical and biological activity.3 Data from this study provided the grounds for the ongoing phase II ALICE study, evaluating iadademstat in combination with azacitidine in newly diagnosed, elderly patients with AML.

Safety and efficacy data from the phase IIa ALICE trial were presented at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, highlighting the safety and tolerability of the regimen, as well as its robust clinical efficacy in elderly patients with AML who were ineligible for intensive chemotherapy. The following outcomes were reported for a total of 13 evaluable patients as per protocol (18 enrolled patients) 4:

  • Overall response rate (ORR) as per protocol: 85%
  • ORR as per intention to treat: 61%
  • Complete remission (CR)/CR with incomplete hematological recovery (CRi) rate: 64%
  • Partial remission rate: 36%
  • Mean time to response: 34 days
  • Proportion of CR/CRi lasting > 6 months: 86%
  • Median duration of response: 308 days

The typical response rate for patients treated with azacitidine monotherapy in this setting is approximately 27%.4 Therefore, the data indicate a synergistic interaction between azacitidine and iadademstat. Recruitment for the ALICE trial has now resumed after disruption caused by the COVID-19 pandemic, and further results are anticipated.5

  1. ORYZON announces FDA orphan drug designation granted to iadademstat for treatment of acute myeloid leukemia. Published Feb 11, 2021. Accessed Feb 15, 2021.
  2. Dai X-J, Liu Y, Xiong X-P, et al. Tranylcypromine based LSD1 inhibitor: summary and prospective. J Med Chem. 2020;63(23):14197-14215. DOI: 1021/acs.jmedchem.0c00919
  3. Salamero O, Montesinos P, Willekens C, et al. First-in-human phase I study of iadademstat (ORY-1001): a first-in-class lysine-specific histone demethylase 1A inhibitor, in relapsed or refractory acute myeloid leukemia. J Clin Oncol. 2020;38(36):4260-4273. DOI: 1200/JCO.19.03250
  4. Salamero O, Somervaille T, Molero A, et al. Robust efficacy signals in elderly aml patients treated with iadademstat in combination with azacitidine (ALICE phase IIa trial). Oral abstract #1916. 62nd ASH Annual Meeting and Exposition; Dec 6, 2020; Virtual.
  5. Oryzon Genomics, S.A. ORYZON presents new robust phase II iadademstat efficacy data in AML at ASH-2020. Published Dec 7, 2020. Accessed Feb 15, 2021.

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