FDA Grants Orphan Drug Designation to NXC-201 for AL Amyloidosis

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The FDA has granted orphan drug designation to the next generation BCMA-directed CAR T-cell therapy NXC-201 for the treatment of patients with amyloid light chain amyloidosis.

The FDA has granted orphan drug designation to the next generation BCMA-directed CAR T-cell therapy NXC-201 (formerly HBI0101) for the treatment of patients with amyloid light chain (AL) amyloidosis.¹

“We are pleased to receive FDA’s orphan drug designation in AL amyloidosis for NXC-201, the only clinical-stage CAR-T cell therapy in development for AL amyloidosis,” Ilya Rachman, MD PhD, executive chairman of Nexcella, stated in a press release. “We are thrilled to potentially expand therapeutic options for relapsed and refractory AL amyloidosis patients, where we have observed to date in our NXC-201 clinical trials a 100% hematologic response rate and demonstrated organ responses in patient hearts, livers and kidneys, for AL amyloidosis patients who received a median of 6 earlier treatments that previously failed to halt the disease.”

NXC-201 is currently under evaluation in the phase 1b/2a NEXICART-1 trial (NCT04720313) in patients with relapsed/refractory multiple myeloma.²

To be eligible for enrollment, patients at least 18 years of age must have relapsed/refractory multiple myeloma following at least 3 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug, and at least 1 antibody therapy. ECOG performance status of 0 to 2 and measurable disease, including at least 1 of the following: serum M-protein level of at least 0.5 g/dL, urine M-protein of at least 200 mg/24h, serum free light chain (FLC) level of at least 5 mg/dL provided serum FLC ratio is abnormal, an evaluable plasmacytoma, and bone marrow plasma cells greater than 20% of total bone marrow cells, were also required. Regarding prior therapy, patients also needed to experience resolution of any non-hematologic toxicities, excluding alopecia and grade 3 neuropathy, to grade 2 or less in severity.

The following doses are being evaluated in dose escalation: 150 x 10⁶ CAR-positive T cells, 450 x 10⁶ CAR-positive T cells, 800 x 10⁶ CAR-positive T cells, and 1200 x 10⁶ CAR-positive T cells. In the dose-expansion portion of the trial, patients will receive between 450 x 10⁶ and 800 x 10⁶ CAR-positive T cells.

Determination of the maximum tolerated dose of NXC-201 in part A and confirmation of the selected dose tested for part B are the primary objectives of the study. Secondary objectives include 2-year overall survival and progression-free survival rates.

In May 2023, results on the first 8 patients enrolled to NEXICART-1 were presented at the 2023 Annual Meeting of The American Society of Gene and Cell Therapy,³ revealing an objective response rate of 100% (n = 8) and a complete response rate of 63% (n = 5) in patients with AL amyloidosis who were relapsed or refractory to daratumumab (Darzalex) following a single infusion of NXC-201 at doses ranging from 150 x 10⁶ to 800 x 10⁶ CAR-positive T cells.

As of data cutoff on May 11, 2023, 1 responder experienced a duration of response exceeding 1 year, at 16.5 months. Moreover, the organ response rate was 75%, and rapid organ response is thought to be a surrogate marker for reduction of free light chain toxicity.

Regarding safety, NXC-201 was well tolerated, with no instances of immune effector cell–associated neurotoxicity syndrome or grade 4 cytokine release syndrome.

“We believe one-time treatment NXC-201 could offer AL amyloidosis patients a convenient therapeutic option,” Gabriel Morris, president of Nexcella, added.

Findings from an additional 30 to 40 patients treated with the recommended phase 2 dose of the agent of 800 x 10⁶ CAR-positive T cells will be presented at the upcoming 2023 IMS Annual Meeting and submitted to the FDA in support of an investigational new drug application for ongoing study of the agent.⁴