CAR T-cell therapy NXC-201 given orphan drug status in EU

High response rate being seen in clinical trial in advanced multiple myeloma

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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NXC-201, an investigational CAR T-cell therapy, has been designated an orphan drug in the European Union (EU) as a potential treatment of multiple myeloma.

This status aims to speed the therapy’s clinical development by providing incentives that include reduced regulatory fees. It also gives access to the EU centralized authorization procedure, wherein the filing of one regulatory application covers all EU countries as well as Iceland, Liechtenstein, and Norway.

Should NXC-201 eventually be approved, it will be granted 10 years of market exclusivity under this designation.

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CAR T-cell therapies are engineered to target myeloma cells

Immix Biopharma, which is developing NXC-201, believes the investigational therapy will be of particular benefit for frail myeloma patients, who often face poorer outcomes and responses to therapy.

“Frail patients … remain an area of unmet medical need and are a significant portion of the relapsed/refractory multiple myeloma population,” Ilya Rachman, MD, PhD, Immix’s CEO, said in a company press release.

“We believe EU orphan drug designation for NXC-201 affirms the potential clinical impact of NXC-201 in this sizable population,” Rachman added.

The therapy also holds orphan drug designation for treating multiple myeloma in the U.S.

Originally developed by researchers at Hadassah Medical Organization in Israel, NXC-201 belongs to a class of treatments called CAR T-cell therapies that have gained traction for the management of multiple myeloma.

Essentially, these treatments involve isolating a person’s immune T-cells — which have innate cancer-fighting abilities — and engineering them in the lab specifically to target myeloma cells.

T-cells in NXC-201 are modified to house a lab-made receptor that binds to BCMA, a protein found at high levels on myeloma cells. When the modified T-cells are returned to a person’s body, they’re expected to bind to myeloma cells and launch an attack against them.

Current CAR T-cell therapies can require hospital stays of a couple of weeks for patients, admitted to receive the treatment, due to certain safety risks. These include cytokine release syndrome, a type of severe immune response that’s common with CAR T-cell therapies.

NXC-201 is expected to minimize such reactions, shortening hospital stays — with the possibility of it being given in an outpatient procedure — enabling more hospitals to offer the treatment and more patients to access it.

90% overall response rate being seen with NXC-201 at optimal dose

The Phase 1b/2 NEXICART-1 clinical trial (NCT04720313), being conducted at the Hadassah University Hospital in Jerusalem, is evaluating the therapy’s safety and effectiveness in up to 160 adults with relapsed and refractory multiple myeloma.

All participants had at least three previous lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and a CD38 inhibitor.

According to Immix, a large proportion of trial participants are considered to be frail.

The study’s Phase 1b portion identified an optimal dose of 800 million cells for its Phase 2 part. Here, the goal is to look at overall response rates, meaning the proportion of patients achieving at least a partial response to treatment.

Previous interim data, at a median follow-up of 5.7 months in February 2023, showed an overall response rate of 82%.

As of a July 2023 data cutoff, 63 myeloma patients had been dosed across the entire trial, with 50 treated at the recommended dose.

With a median follow-up of nearly one year, an overall response rate of 90% was seen among trial patients given the optimal dose. More than half of this group (58%) achieved a complete response, where the cancer is virtually eradicated.

Most patients (70%) also were negative for minimal residual disease, or the small number of myeloma cells that can remain after treatment and cause a relapse.

Cytokine release syndrome reaction resolved in same day it emerged

Prior use of BCMA-targeted therapies or the presence of extra-medullary disease were associated with a “worse outcome,” but still “high response rates” of about 75%, the researchers reported. Extra-medullary disease is marked by cancer that has spread beyond the bone marrow.

At nearly one year after treatment (11.9 months), the median survival without cancer progression was 10.6 months and median overall survival had not been reached, meaning most patients were still alive.

The treatment’s safety profile was considered to be manageable, overall. While cytokine release syndrome was reported in 96% of patients, most cases were not considered severe. Immix considers that NXC-201 might be the world’s first CAR T-cell therapy with a “single day” of this syndrome, with average immune reactions both emerging and resolving within one day.

“We believe NXC-201’s observed favorable tolerability profile and ‘Single Day CRS’ [cytokine release syndrome] across a robust clinical dataset could enable an attractive option for frail relapsed/refractory multiple myeloma patients,” said Gabriel Morris, Immix’s chief financial officer.

Complete data collection in the NEXICART-1 trial is likely in 2025, and the study is expected to finish in early 2026.