Nexcella’s Light Chain Amyloidosis CAR-T NXC-201 Expands Clinical Trial Activities Into the US

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The CAR-T was already being assessed in the ongoing phase 1a/1b NEXICART-1 clinical trial in Israel ahead of this IND clearance by the FDA.

Nexcella’s NXC-201 (formerly referred to as HBI0101), an investigational autologous chimeric antigen receptor T-cell (CAR-T) therapy that targets B-cell maturation antigen (BCMA), has received clearance from the FDA of an investigational new drug (IND) application for the NEXICART-2 (NCT06097832) clinical trial in patients with light chain (AL) amyloidosis.1

Although this will be the first clinical evaluation of NXC-201 in the United States, the CAR-T is already being assessed in patients with AL amyloidosis and relapsed/refractory (r/r) multiple myeloma (MM) in the ongoing phase 1a/1b NEXICART-1 clinical trial (NCT04720313), a single-center study taking place at the Hadassah University Hospital in Jerusalem, Israel. In total, 72 patients have been treated with NXC-201 so far: 9 with AL amyloidosis and the remainder with MM. Among the 9 patients with AL amyloidosis who had been treated with a median of 6 previous lines of therapy, the overall response rate (ORR) following treatment with NXC-201 was 100% as of the September 20, 2023, data cut-off. One of the patients received a dose of 150×106 CAR T-cells, 2 of the patients received a dose of 450×106 CAR T-cells, and 6 of the patients received a dose of 800×106 CAR T-cells.

“Building on encouraging NXC-201 clinical data to-date, we are thrilled that multiple leading US sites are currently planning to enroll patients in the coming months,” Ilya Rachman, MD, PhD, the executive chairman of Nexcella, said in a statement.1 “No approved treatment options currently exist for r/r AL amyloidosis patients.”

At the American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting, held May 16-20, in Los Angeles, California, Nathalie Asherie, PhD, of the Department of Bone Marrow Transplantation and Cancer Immunotherapy at Hadassah Medical Center, reported that among 8 patients with AL amyloidosis included in the efficacy analysis at that time, 5 patients achieved a complete hematologic response, 2 achieved a very good partial hematologic response, and 1 achieved a partial hematologic response.2 In terms of safety, 6 of the 8 patients experienced cytokine release syndrome (CRS); excepting 2 cases of grade 3 CRS, all CRS cases were grade 1-2. Notably, there were no cases of immune effector cell-associated neurotoxicity syndrome reported in the 8 patients. Asherie characterized the safety profile of NXC-201 as “clinically manageable,” pointing out that both patients with grade 3 CRS required high flow oxygen use and 1 required vasopressor use and also noting that 2 of the 8 patients experienced organ deterioration.

Key Takeaways

  • Nexcella's investigational CAR-T therapy, NXC-201, targeting B-cell maturation antigen (BCMA), has received FDA clearance of an investigational new drug (IND) application for the NEXICART-2 clinical trial.
  • The ongoing NEXICART-1 trial in Israel has shown promising results for NXC-201 in patients with AL amyloidosis and relapsed/refractory multiple myeloma (MM), with a 100% overall response rate (ORR) in the AL amyloidosis patients treated.
  • The safety profile of NXC-201, including a lack of neurotoxicity, positions it favorably for potential expansion into autoimmune indications beyond AL amyloidosis, such as systemic lupus erythematosus, myasthenia gravis, and multiple sclerosis.

“We credit our world-class cell therapy expert team in achieving this IND clearance inline with our previously communicated timelines,” Gabriel Morris, the president of Nexcella, added to the statement.1 “NXC-201’s favorable tolerability profile, including overcoming neurotoxicity, potentially enables expansion beyond AL amyloidosis into autoimmune indications.”

A lack of neurotoxicity was also observed in patients with r/r MM treated in NEXICART-1; in August 2023, Nexcella noted that in more than 50 patients dosed by that time, no neurotoxicity had been reported.3 The company now plans to explore the potential of NXC-201 in autoimmune indications including systemic lupus erythematosus, myasthenia gravis, and multiple sclerosis.1 NXC-201 has been granted orphan drug designation by the FDA for both MM and AL amyloidosis.3 The US IND clearance for NXC-201 was preceded by several preliminary steps announced by Nexcella earlier this year; these included completion of a preIND meeting with the FDA in June and finishing manufacturing of the first engineering batch for NXC-201 in the US in July.4,5

REFERENCES
1. Nexcella announces FDA approval of IND application for CAR-T NXC-201, enabling U.S. patient dosing. News release. Nexcella, Inc. November 21, 2023. Accessed November 21, 2023. https://nexcella.com/2023/11/21/nexcella-announces-fda-approval-of-ind-application-for-car-t-nxc-201-enabling-u-s-patient-dosing/
2. Asherie N. BCMA-targeted CART (HBI0101), a safe and efficacious novel modality of treatment for LC amyloidosis patients. Presented at: American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting. May 16-20, 2023; Los Angeles, CA. Oral abstract session.
3. U.S. Food and Drug Administration approves orphan drug designation for NXC-201 as a treatment for multiple myeloma. News release. Nexcella, Inc. August 23, 2023. Accessed August 24, 2023. https://nexcella.com/2023/08/23/u-s-food-and-drug-administration-approves-orphan-drug-designation-for-nxc-201-as-a-treatment-for-multiple-myeloma/
4. Nexcella completes pre-IND meeting with FDA on NXC-201 US clinical trial. News release. Nexcella, Inc. June 26, 2023. Accessed August 24, 2023. https://nexcella.com/2023/06/26/nexcella-completes-pre-ind-meeting-with-fda-on-nxc-201-us-clinical-trial/
5. Nexcella completes initial NXC-201 engineering batch at its U.S. CAR-T manufacturing site. News release. Nexcella, Inc. July 10, 2023. Accessed August 24, 2023. https://nexcella.com/2023/07/10/nexcella-completes-initial-nxc-201-engineering-batch-at-its-u-s-car-t-manufacturing-site/

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