NXC-201 Receives Orphan Drug Designation in the European Union for Multiple Myeloma

The European Commission (EC) has granted orphan drug designation to the BCMA-targeted CAR T-cell therapy NXC-201 (formerly HBI0101) for the treatment of patients with multiple myeloma.^1,2

The safety and efficacy of NXC-201 are currently being evaluated in the ongoing phase 1b/2a NEXICART-1 trial (NCT04720313) in adult patients with BCMA-expressing, relapsed/refractory multiple myeloma and amyloid light chain (AL) amyloidosis.²

Findings from a study assessing the real-world impact of frailty on patient outcomes following CAR T-cell therapy demonstrated that commercial CAR T products generated a median progression-free survival (PFS) of 6.9 months in patients with relapsed/refractory multiple myeloma who were considered frail at the time of infusion (n = 83/136).³ The development of NXC-201 may address this unmet need for more effective agents for this subset of patients. If approved, this agent could be administered as outpatient therapy because of its favorable safety profile, potentially reducing hospitalization and related costs.²

“Frail patients, heavily represented in our NEXICART-1 clinical trial, remain an area of unmet medical need and are a significant portion of the relapsed/refractory multiple myeloma population,” Ilya Rachman, MD, PhD, chief executive officer at Immix Biopharma, stated in a news release.¹ “We believe European Union orphan drug designation for NXC-201 affirms the potential clinical impact of NXC-201 in this sizable population.”

The open-label NEXICART-1 study is enrolling patients with relapsed/refractory multiple myeloma who have previously received 3 or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and at least 1 antibody therapy.⁴ Patients are required to be at least 18 years of age, have an ECOG performance status of 0 to 2, and have had any non-hematologic toxicities from previous treatments recover to grade 2 or less in severity except for alopecia and grade 3 neuropathy. Measurable disease was also required, including 1 or more of the following: serum M-protein level of at least 0.5 g/dL, urine M-protein of at least 200 mg per 24 hours, 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.

In the dose-escalation phase, the CAR T-cell therapy was administered at escalating doses of 150 x 10⁶, 450 x 10⁶, 800 x 10⁶, and 1200 x 10⁶ CAR-positive T cells. The dose-expansion phase will include a dose between 450 × 10⁶ to 800 × 10⁶ CAR-positive T cells.

The primary objective of the phase 1b portion of the trial was to characterize safety and identify the recommended phase 2 dose (RP2D) and maximum tolerated dose of NXC-201.^2,4 In the phase 2 portion, the primary objective is to determine the overall response rate (ORR) and duration of response in the multiple myeloma population and ORR in the AL amyloidosis population. Secondary end points include overall survival (OS) and PFS according to the International Myeloma Working Group Uniform Response Criteria.

Updated clinical data in 63 patients with relapsed/refractory multiple myeloma from NEXICART-1 were presented at the 2023 ASH Annual Meeting & Exposition.⁵ Of the 51 patients who underwent lymphocyte apheresis in this cohort, 98% were infused, the NXC-201 production success rate was 100%, and the manufacturing time for all patients was 10 days.

At a data cutoff of July 17, 2023, and a median follow-up of 11.9 months (range: 0.6-19.0), the ORR in patients who received the RP2D of 800 x 10⁶ CAR-positive T cells regardless of prior BCMA-targeted therapy exposure (n = 50) was 90%.^2,5 This included a 58% complete response rate, a 20% very good partial response (PR) rate, and a 12% PR rate. The median PFS in the overall cohort was 10.6 months, and the median OS was not reached. Minimal residual disease negativity was achieved at day 30 or higher in 70% of patients.⁵

In patients who received the 800 x 10⁶ dose and were not previously exposed to BCMA-targeted therapy (n = 38), the ORR was 95%, and the median PFS was 12.9 months.² The ORRs for patients who received the 150 x 10⁶ (n = 6) and 450 x 10⁶ (n = 7) CAR T-cell doses were 50% and 86%, respectively. NXC-201 also demonstrated a manageable safety profile, although grade 3/4 hematological toxicities were common.⁵

In August 2023, the FDA granted an orphan drug designation to NXC-201 for use in patients with multiple myeloma.⁶ The agent subsequently received orphan drug designation as a potential therapeutic for patients with AL amyloidosis from the FDA in September 2023 and the EC in February 2024.^7,8

“We believe NXC-201’s observed favorable tolerability profile and ‘single day [cytokine release syndrome]’ across a robust clinical dataset could enable an attractive option for frail relapsed/refractory multiple myeloma patients in addition to our lead indication, relapsed/refractory AL amyloidosis, and our active NXC-201 expansion into other autoimmune diseases,” Gabriel Morris, chief financial officer of Immix Biopharma, added in the news release.¹

References

1. Immix Biopharma awarded European Union orphan drug designation for NXC-201 in multiple myeloma. News release. Immix Biopharma. April 29, 2024. Accessed May 3, 2024. https://immixbio.com/immix-biopharma-awarded-european-union-orphan-drug-designation-for-nxc-201-in-multiple-myeloma/
2. Nexcella announces 72-patient NXC-201 clinical data at the IMS 20th Annual Meeting, 95% overall response rate in multiple myeloma. News release. Nexcella, Inc. October 2, 2023. Accessed May 3, 2024. https://nexcella.com/2023/10/02/nexcella-announces-72-patient-nxc-201-clinical-data-at-the-ims-20th-annual-meeting-95-overall-response-rate-in-multiple-myeloma/
3. Davis JA, Dima D, Ahmed N, et al. Impact of frailty on outcomes after chimeric antigen receptor T cell therapy for patients with relapsed/refractory multiple myeloma. Transplant Cell Ther. 2024;30(3):298-305. doi:10.1016/j.jtct.2023.12.015
4. NXC-201 (formerly HBI0101) multiple myeloma. ClinicalTrials.gov. Updated May 3, 2023. Accessed May 3, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT04720313
5. Lebel E, Asherie N, Erenfeld SK, et al. Efficacy and safety of a locally produced novel anti-BCMA chimeric antigen receptor T-cell (CART) (HBI0101) for the treatment of relapsed and refractory multiple myeloma. Blood. 2023;142(suppl 1):4852. doi:10.1182/blood-2023-185069
6. 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 May 3, 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/
7. U.S. 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 May 3, 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/
8. Immix Biopharma awarded European Union orphan drug designation for NXC-201 in AL amyloidosis. News release. Immix Biopharma, Inc. February 7, 2024. Accessed May 3, 2024. https://immixbio.com/immix-biopharma-awarded-european-union-orphan-drug-designation-for-nxc-201-in-al-amyloidosis/