FDA Grants Orphan Drug Designation to IGNK001 in Acute Myeloid Leukemia


With an FDA orphan drug designation now granted to IGNK001, clinical trials investigating the agent in acute myeloid leukemia are planned to initiate in the US.

FDA logo
  • The FDA has granted an orphan drug designation to IGNK001 (Gengleucel).
  • The investigational therapy being developed for the treatment of patients with acute myeloid leukemia (AML).
  • Clinical trials will continue to evaluate the IGNK001 in the US with the goal of completing the studies by December 2027.

An orphan drug designation has been granted to IGNK001 by the FDA for the treatment of patients with AML, according to Ingenium Therapeutics.1

“We are delighted to have received orphan drug designation for IGNK001 from the FDA, recognizing the potential of our innovative [natural killer (NK)] cell therapy technology,” said Ko Jin-ok, chief executive officer of Ingenium Therapeutics, in a press release. “[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.”

IGNK001 is an allogeneic NK cell therapy.2 While traditional methods for NK cell therapy use feeder cells to cultivate small numbers of isolated NK cells, this manufacturing process for IGNK001 leads to memory NK cells with higher expression of activating receptors. The novel method expands NK cells through targeted differentiation of other immune cells. This feeder cell-free process yields large quantities of healthy NK cells while avoiding exhaustion.

Acute myeloid leukemia cells: © LASZLO - stock.adobe.com

Acute myeloid leukemia cells: © LASZLO - stock.adobe.com

In addition to memory NK cells that have higher expression of activating receptors, the IGNK001 manufacturing process results in higher granzyme B and perforin 1 production compared with normal NK cells. These cells have also shown to have increased production of IFN-γ.

The mass-produced, allogeneic NK cell therapy has already demonstrated potent anticancer effects with high purity and activity.1 Its safety and efficacy have also been evaluated in a number of clinical trials.

Most recently, a single-center, open-label, random comparison, phase 2b study (NCT02477787) evaluated haploidentical hematopoietic cell transplantation and subsequent donor NK cell infusion in patients with high-risk, refractory AML and myelodysplastic syndromes.3 Patients were required to be aged 19 years or older with a Karnofsky performance status of at least 70.

In the experimental arm (n = 40), patients were given donor-derived NK cell infusions twice on days 13 and 20 after haploidentical hematopoietic cell transplantation. On day 13, the donor NK cell infusion was given at a dose which ranged from 1 x 108/kg to 2 x 108/kg, and on day 20, the donor NK cell infusion was given at a cell dose of up to 5 x 108/kg. The control arm included 36 patients who underwent haploidentical hematopoietic cell transplantation alone.

Investigators assessed the primary end point of the number of patients who experienced AML progression or recurrence after hematopoietic cell transplantation. Secondary end points explored in the study 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.

Findings from the intention-to-treat analysis showed that there was lower 30-month cumulative incidence of disease progression among those in the NK group vs the control group. These rates were 35% vs 61%, respectively (subdistribution HR, 0.50; P = .040).4

Three months post hematopoietic cell transplantation, those who received NK cells had a 1.8- and 2.6-fold higher median absolute blood count of NK cells and T cells compared with those who received hematopoietic cell transplantation alone. Looking at a single-cell RNA sequencing analysis in 7 patients, findings showed there to be an increase in memory-like NK cells among those given the NK cell infusion. This in turn expanded the CD8-positive effector memory T cells.

These findings, which led to IGNK001’s approval from the Korean Ministry of Food and Drug Safety for phase 2 clinical trials, now also are leading to the initiation of a sponsored clinical trial to support the conditional marketing approval of IGNK001.3

1. Ingenium Therapeutics novel NK cell therapy receives orphan drug designation from FDA. News release. Ingenium Therapeutics. April 30, 2024. Accessed May 2, 2024. https://tinyurl.com/mu4cnukv
2. Our technology. Ingenium Therapeutics. Accessed May 2, 2024. https://ingeniumcell.co.kr/en/science/our-technology/
3. Clinical trials. Ingenium Therapeutics. Accessed April 2, 2024. https://ingeniumcell.co.kr/en/science/clinical/
4. 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
Related Videos
Related Content