European Commission Grants Orphan Drug Designation to NXC-201 for AL Amyloidosis

The BCMA-targeted CAR T-cell therapy, NXC-201 (formerly HBI0101), has received orphan drug designation (ODD) from the European Commission for use as a potential therapeutic option in patients with amyloid light-chain (AL) amyloidosis.¹

The agent is under examination in an ongoing phase 1/2 study (NCT04720313). Early data from the trial were shared during the 2023 International Myeloma Society Annual Meeting and indicated that elicited hematologic and organ responses with acceptable safety in patients with AL amyloidosis, including frail patients, although deaths due to cardiac disease occurred frequently during the first year of treatment.²

“European Union ODD for NXC-201 represents an important milestone in our global strategy,” Ilya Rachman, MD PhD, chief executive officer of Immix Biopharma, stated in a press release.¹ “We believe we are addressing an urgent need to establish a new potential one-time treatment option for relapsed/refractory AL amyloidosis patients.”

Patients with relapsed or refractory AL amyloidosis were enrolled in the phase 1 portion of the study after the safety and efficacy of the product were showcased in those with relapsed or refractory multiple myeloma.²

To participate, patients must have previously received 3 lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. Patients with AL amyloidosis needed to have a platelet count of 30 x 10⁹/L, a creatine clearance of at least 20 mL/min, a left ventricular ejection fraction of 40% or higher, and an ECOG performance status of 0 to 2.

The manufacturing time for the product was 10 days. Patients underwent lymphodepletion consisting of 25 mg/m² of fludarabine and 250 mg/m² of on days –5 to –3 prior to the infusion of the CAR T-cell therapy. Notably, bendamustine was given at 90 mg/m² on days –4 and –3 for patients who had a creatinine clearance of less than 30 mL/min.

In the dose-escalation, phase 1a portion of the study, NXC-201 was administered at target doses of 150 x 10⁶ CAR T-cells (n = 1), 450 x 10⁶ CAR T cells (n = 2), and 800 x 10⁶ CAR T cells (n = 1). Five patients then received 800 x 10⁶ CAR T cells in phase 1b/2. Among the 9 patients with AL amyloidosis enrolled, 2 were treated on a compassionate basis.

Among the cohort of 9 patients with AL amyloidosis, the median age was 64 years, and 6 patients were male. Two patients had concurrent multiple myeloma, and 7 had cardiac involvement. New York Heart Association (NYHA) stages included I (n = 2), II (n = 2), III (n = 2), and IV (n = 3). Notable cytogenetics included t(11;14) (n = 4), t(14;16) (n = 1), 14q deletions (n = 2), and 17p deletions (n = 1). Mayo Amyloidosis stages included I (n = 3), II (n = 2), IIIA (n = 3), and IIIB (n = 1). After treatment, 5 patients experienced an improvement in NYHA stage, including 2 patients who improved from stage III to stage II, 2 patients who improved from stage IV to stage III, and 1 patient who saw a reduction from stage IV to stage II.

The 9 evaluable patients experienced a hematologic overall response rate (ORR) of 100%, which included 6 complete responses, 2 very good partial responses (VGPRs), and 1 partial response (PR). At day 30, all 6 patients in CR were minimal residual disease negative. Organ responses were achieved by 5 patients.

During follow-up, a total of 5 patients died because of cardiac disease, including 3 who had progressive disease, 1 who was in VGPR, and 1 who was in PR. One additional patient died because of COVID-19 while in CR. Among those who died, overall survival (OS) ranged from 3.3 months to 12.2 months.

In terms of safety, 7 patients experienced cytokine release syndrome (CRS) that was grade 1 (n = 2), grade 2 (n = 3), or grade 3 (n = 2). The median time to onset of CRS was 2 days (range, 1-3), and the median duration was 1 day (range, 1-4). Six of 7 patients who experienced CRS received tocilizumab (Actemra). No instances of immune effector cell–associated neurotoxicity syndrome occurred.

“We believe NXC-201’s observed favorable tolerability profile and ‘Single Day CRS’ across a robust clinical dataset to-date enables our observed complete responses [ongoing] in heavily pretreated relapsed/refractory AL amyloidosis patients and potential expansion into other autoimmune diseases,” Gabriel Morris, chief financial officer of Immix Biopharma, added in the press release.¹

In August 2023, the FDA granted an orphan drug designation to NXC-201 for use in patients with multiple myeloma.³ The next month, the agent received another orphan drug designation from the regulatory agency for those with AL amyloidosis.⁴

References

1. Immix Biopharma awarded European Union orphan drug designation for NXC-201 in AL amyloidosis. News release. Immix Biopharma, Inc. February 7, 2024. Accessed February 8, 2024. https://immixbio.com/immix-biopharma-awarded-european-union-orphan-drug-designation-for-nxc-201-in-al-amyloidosis/
2. Lebel E, Erenfeld SK, Asherie N et al. Feasibility of a novel academic anti-BCMA chimeric antigen receptor T-cell (CART) (HBI0101) for the treatment of relapsed and refractory AL amyloidosis. Presented at: 2023 International Myeloma Society Annual Meeting; September 27-30, 2023; Athens, Greece. Abstract OA-34.
3. US 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 February 8, 2024. 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. US Food and Drug Administration approves orphan drug designation for Nexcella NXC-201 as a treatment for amyloid light chain (AL) amyloidosis. News release. Nexcella, Inc. September 21, 2023. Accessed February 8, 2024. https://nexcella.com/2023/09/21/u-s-food-and-drug-administration-approves-orphan-drug-designation-for-nexcella-nxc-201-as-a-treatment-for-amyloid-light-chain-al-amyloidosis/