NK Cell Therapy IGNK001 Receives FDA Orphan Drug Designation for AML


The investigational therapy IGNK001 has received orphan drug designation from the FDA for patients with acute myeloid leukemia.



The FDA has granted orphan drug designation to the investigational therapy IGNK001 (Gengleucel) for patients with acute myeloid leukemia (AML).1

IGNK001 is a mass-produced, allogeneic natural killer (NK) cell therapy that is derived from healthy donors. The IGNK001 manufacturing process results in memory NK cells that have higher expression of activating receptors, as well as higher granzyme B and perforin 1 production, compared with normal NK cells.2 These cells have also been demonstrated to have increased production of IFN-γ.

“We are delighted to have received orphan drug designation for IGNK001 from the FDA, recognizing the potential of our innovative NK cell therapy technology, Ko Jin-ok, chief executive officer of Ingenium Therapeutics, said in a news release.1 “[IGNK001] has already received approval from the Korean Ministry of Food and Drug Safety for phase 2 clinical trials, and we are preparing to initiate clinical trials in the US targeting 80 subjects with the goal of completing the studies by December 2027.”

Since 2007, the safety and efficacy of IGNK001 have been evaluated in several investigator-initiated clinical trials, the most recent of which was a single-center, open-label, phase 2b trial (NCT02477787) of haploidentical hematopoietic cell transplantation and subsequent donor NK cell infusion in patients ages 19 years or older with high-risk, refractory AML and myelodysplastic syndromes and a Karnofsky performance status of at least 70.3,4 Patients were excluded from the study if they had abnormal liver function, abnormal renal function, clinically evident pulmonary or cardiac dysfunction, an infection that was progressive despite the use of appropriate antimicrobial treatment, or hypersensitivity to gentamicin.4 Patients could not be pregnant or lactating and could not have received prior allogeneic cell therapy.

Patients in the experimental arm (n = 40) received donor-derived NK cell infusions around days 13 and 20 after haploidentical hematopoietic cell transplantation. On day 13, the donor NK cell infusion was given at a cell dose ranging from 1 x 108/kg to 2 x 108/kg, or approximately half the amount generated. On day 20, the donor NK cell infusion was given at a cell dose of up to 5 x 108/kg. Patients in the control arm (n = 36) underwent haploidentical hematopoietic cell transplantation alone.

The primary end point of this trial was the number of patients who experienced AML progression or recurrence after hematopoietic cell transplantation. Secondary end points included the number of patients who achieved engraftment after hematopoietic cell transplantation, the number of patients who developed acute graft-vs-host disease (GVHD) and chronic GVHD, the number of patients who experienced donor NK cell infusion–associated toxicity, and the number of patients who died after hematopoietic cell transplantation without AML progression.

The intention-to-treat analysis demonstrated a lower 30-month cumulative incidence of disease progression in the NK arm vs the control arm, at 35% vs 61%, respectively (subdistribution HR, 0.50; P = .040).5 At 3 months after hematopoietic cell transplantation, the patients who received NK cells had a 1.8-fold higher median absolute blood count of NK cells and a 2.6-fold higher median absolute blood count of T cells vs the patients who received hematopoietic cell transplantation alone. Moreover, a single-cell RNA sequencing analysis in 7 patients demonstrated an increase in memory-like NK cells in patients who received NK cell infusion, which expanded the CD8-positiveeffector memory T cells.

These findings led to the establishment of product specifications and a Good Manufacturing Practice process, as well as approval from Korean regulators to initiate a sponsored clinical trial to support the conditional marketing approval of IGNK001.3 This trial will be conducted at 4 sites.


  1. Ingenium Therapeutics novel NK cell therapy receives orphan drug designation from FDA. News release. Ingenium Therapeutics. April 30, 2024. Accessed April 30, 2024. https://www.prnewswire.com/news-releases/ingenium-therapeutics-novel-nk-cell-therapy-receives-orphan-drug-designation-from-fda-302131237.html
  2. Our technology. Ingenium Therapeutics. Accessed April 30, 2024. https://ingeniumcell.co.kr/en/science/our-technology/
  3. Clinical trials. Ingenium Therapeutics. Accessed April 30, 2024. https://ingeniumcell.co.kr/en/science/clinical/
  4. Randomized study of haploidentical hct and subsequent donor nk cell infusion in high-risk AML and MDS (DNKI-4). ClinicalTrials.gov. Updated July 8, 2019. Accessed April 30, 2024. https://clinicaltrials.gov/study/NCT02477787
  5. Lee KH, Yoon SR, Gong JR, et al. The infusion of ex vivo, interleukin-15 and -21-activated donor NK cells after haploidentical HCT in high-risk AML and MDS patients-a randomized trial. Leukemia. 2023;37(4):807-819. doi:10.1038/s41375-023-01849-5

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