FDA Grants ODD to Novel LSD1 Inhibitor in Acute Myeloid Leukemia


The FDA granted Orphan Drug designation to first-in-class LSD1 inhibitor iadademstat, for the treatment of patients with acute myeloid leukemia.

The FDA granted Orphan Drug designation to first-in-class LSD1 inhibitor iadademstat (ORY-1001), for the treatment of patients with acute myeloid leukemia (AML), according to a press release from the drug developer, Oryzon Genomics, S.A.1

“Receiving Orphan Drug Designation for iadademstat in AML is an important recognition of the role that new drugs with new mechanisms of action may bring to this patient community, where we do not yet have any potentially curative medicines besides stem cell transplant. Iadademstat is showing a high overall response rate of 85% in our ongoing clinical phase 2 study ALICE, with a rapid onset of action and with durable responses. In addition, we have seen a good safety and tolerability profile in the combination treatment with azacitidine. Future phase 2 clinical trials in further combination treatments of AML are planned for the second half of this year,” said Torsten Hoffmann, global head of Research and Development and chief scientific officer, Oryzon Genomics, S.A., in a statement.

Iadademstat is an investigational, oral, small molecule covalent inhibitor of the epigenetic enzyme LSD1. When investigated preclinically, the agent showed safety, tolerability, and signals of antileukemic activity. Iadademstat is now being investigated in the phase 2a ALICE clinical trial as treatment of elderly patients with AML, in combination with azacitidine (Vidaza).

Results from 13 evaluable patients in the study were presented during the 2020 American Society of Hematology (ASH) Annual Meeting. The cohort received iadademstat at 90 μg/m2/day. On treatment, patients were evaluated for response-related outcomes, including overall response rate (ORR), time to response (TTR), and duration of response (DOR). The end points of the ongoing study are hematological improvement and overall survival. Pharmacokinetics and pharmacodynamics were also assessed in this study.2

The patients being evaluated are ≥ 60 years of age with AML according to World Health Organization (WHO) classification. At screening, patients enrolled are required to be ineligible for intensive chemotherapy and be naïve to AML therapies other than hydroxyurea (Hydrea).

In data from the ALICE study presented at ASH 2020, 13 of 18 patients had completed at least 1 bone marrow evaluation. Among these patients the ORR was 77%, with 4 complete remissions (CRs), 2 with incomplete hematologic recovery (CRi), and 4 partial responses.

The mean duration of treatment is 20 weeks and the mean time to response is 37 days. The progression-free survival for patients in remission is 250 days with the longest CR lasting more than 550 days. Patients with longer treatment durations have overcome dependency on blood transfusions as well.

In terms of safety, the most common adverse events (AEs) were neutropenia and thrombocytopenia; only 3 nonhematologic AEs of asthenia, dysgeusia, and weight reduction were observed. Thirty-eight serious AEs were reported, only 2 of which were considered related to treatment.

Study investigators concluded from the analysis of ALICE that iadademstat in combination with azacitidine is a promising candidate for elderly patients with AML who are treatment naïve and compares favorably to historical response rates with azacitidine alone.

ALICE is a dose-finding study. In part 1 of the trial, a maximum of 18 patients will be dosed with iadademstat of 90 μg/m2/day in combination with azacitidine. Throughout treatment, the dose of iadademstat may be increased or decrease based upon the occurrence of dose-limiting toxicities. The study is evaluated safety to find the recommended phase 2 dose and once it is determined, 18 patients will be enrolled into an expansion cohort.

By holding an Orphan Drug status, it will allow iadademstat’s developer market exclusivity if it is FDA approved later on, as well as exemption from FDA application fees and tax credits for qualified clinical trials.

The promise observed with iadademstat in patients with AML also landed the drug an Orphan Drug Designation from the European Medicines Agency.


1. ORYZON announces FDA Orphan Drug Designation granted to iadademstat for treatment of acute myeloid leukemia. New release. February 11, 2021. Accessed February 11, 2021. https://bit.ly/3tPP5w1

2. Salamero O, Somervaille T, Molero A, et al. 1916 Robust efficacy signals in elderly aml patients treated with iadademstat in combination with azacitidine (ALICE Phase IIa Trial). Presented at: 2020 ASH Annual Meeting; December 5-8, 2020. Abstract 1916.

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