BCMA-Directed CAR-T NXC-201 Gets FDA Orphan Drug Designation in Multiple Myeloma


Because of the lack of neurotoxicity seen in patients treated thus far, Nexcella believes NXC-201 may have potential to serve as an outpatient treatment.

Nexcella’s NXC-201 (HBI0101), an investigational autologous chimeric antigen receptor (CAR) T-cell therapy which targets B-cell maturation antigen (BCMA) being evaluated for the treatment of relapsed/refractory (r/r) multiple myeloma (MM) and light chain amyloidosis (AL), has received orphan drug designation from the FDA for MM.1

NXC-201 is being evaluated in a collaboration with Hadassah Medical Organization in the phase 1a/1b NEXICART-1 clinical trial (NCT04720313) in Jerusalem, Israel. The study includes both patients with MM and AL. Because of the lack of neurotoxicity seen in patients treated thus far, Nexcella believes NXC-201 may have potential to serve as an outpatient treatment.

“We are pleased to receive FDA’s orphan drug designation in MM for NXC-201, the only clinical-stage BCMA-targeted CAR-T cell therapy with no neurotoxicity observed in over 50 patients dosed to date,” Ilya Rachman, MD, PhD, the executive chairman of Nexcella, said in a statement.1 “We are thrilled to potentially expand therapeutic options for MM patients, while eliminating the most feared adverse effect of this therapeutic class, neurotoxicity.”

Among patients with r/r MM treated in NEXICART-1 as of the February 9, 2023, data cutoff, NXC-201 demonstrated a 92% overall response rate (ORR) in patients with r/r MM who received the therapeutic dose of 800 million CAR+ T-cells and had not previously been treated with a BCMA-directed therapy.2 The median progression free survival for this group was 12.3 months. Furthermore, among 37 patients who received the therapeutic dose, regardless of prior treatment with BCMA-directed therapy, the ORR was 87% (n = 32) and the complete response rate was 57% (n = 21).

Notably, NXC-201 showed an even higher response rate in AL in NEXICART-1. 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 the 8 patients with AL included in the efficacy analysis, all 8 achieved a response. This included 5 who achieved a complete hematologic response, 2 who achieved a very good partial hematologic response, and 1 who achieved a partial hematologic response.

“We continue to be very encouraged by NXC-201 clinical results,” principal investigator Polina Stepensky, MD, director, Department of Bone Marrow Transplantation and Immunotherapy for Adults and Children, Hadassah Medical Organization, said in an April, 2023, statement.2 “In MM, these data are compelling as the overall response rate for ABECMA was 72% in its pivotal KarMMa trial with 100 patients in r/r MM. In AL , NXC-201’s very promising response could offer hope to patients who have already been treated with a 4-drug standard-of-care combination incorporating DARZALEX. In particular, NXC-201 may offer a valuable option for both multiple myeloma and AL patients who have progressed on standards of care.”

Nexcella is currently making moves towards initiating a clinical trial in the United States to evaluate NXC-201 in American patients with r/r MM and AL. In June of this year, the company stated that it had held a preInvestigational New Drug meeting with the FDA to discuss the topic.4 Later, in July, Nexcella reported that the first engineering batch for NXC-201 in the US had finished manufacturing.5

“The completion of our first US engineering batch is a significant step towards expanding our phase 1b/2a NEXICART clinical trial to the United States as we work to bring NXC-201 to American patients in need,” Rachman said in a July, 2023, statement.5

1. 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/
2. Nexcella announces positive 58-patient NXC- 201 clinical data: 100% overall response rate in light chain (AL) amyloidosis; 92% overall response rate in multiple myeloma at the EBMT 49th Annual Meeting in Paris. News release. Nexcella, Inc. April 26, 2023. Accessed August 24, 2023. https://nexcella.com/2023/04/26/nexcella-announces-positive-58-patient-nxc-201-clinical-data-100-overall-response-rate-in-light-chain-al-amyloidosis-92-overall-response-rate-in-multiple-myeloma-at-the-ebmt-49th-annual-meeting-i/
3. 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.
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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