CD5 CAR-T Cell Therapy Receives FDA Orphan Drug Designation for T-Cell Lymphoma

The FDA has granted orphan drug designation to MB-105 (March Biosciences), a first-in-class CD5-targeted chimeric antigen receptor (CAR) T-cell therapy for the treatment of relapsed or refractory CD5-positive T-cell lymphoma (TCL).¹

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“Beyond an important regulatory milestone, securing orphan drug designation for MB-105 from the FDA underscores the critical need for new therapeutic options for patients with TCL,” said Sarah Hein, co-founder and chief executive officer of March Biosciences, in a news release.¹

Relapsed CD5-positive TCL indicates a type of TCL where the cancer cells have returned after initial treatment, while refractory refers to cancer that has not responded to any treatment. Individuals with relapsed or refractory CD5-positive TCL often experience a poor prognosis and require advanced therapeutic strategies.²

TCL is challenging to treat due to the potential for on-target, off-target tumor activity, which could cause unwanted activity against normal T-cells and severe immunodeficiency. A shared expression of targetable antigens between the malignant and normal T-cells are known to impact the activity and affect CAR T-cell production, according to study authors.³

However, using CD5 as a target could result in a greater prognosis as it is widely expressed in T-cell malignancies and most TCL subtypes. Additionally, the study authors noted that CD5 is highly expressed in T-cell acute lymphoblastic leukemia (T-ALL), mantle cell lymphoma (MCL), and chronic lymphocytic leukemia (CLL).³

As an autologous CD5-targeted CAR-T cell therapy, MB-105 could address barriers to the application of CAR technologies to T-cell malignancies.³ The study authors noted that the therapy includes a proprietary CAR design that permits selective targeting of malignant cells to preserve some normal T-cell functions. Additionally, MB-105 is in development for CD5-positive hematologic malignancies, such as TCL, T-ALL, CLL, and MCL.¹

An ongoing phase 1 MAGENTA clinical trial (NCT03081910) for relapsed or refractory TCL and T-ALL is currently being evaluated, assessing how long cells lasts when the CD5 chimeric receptor with CD28 is added to the individual’s T cells or the previous bone marrow transplant donor’s T cells.^1,3

The study included a total of 17 individuals with TCL. CD5 CAR T-cells were manufactured for 13 out of the 14 attempted lines and administered to 9 individuals. The results demonstrated an overall response rate of 44% with complete response achieved in 2 individuals. The findings from the study suggest that CD5 CAR T-cells are safe and can provide clinical response among individuals with relapsed or refractory CD5-positive TCL.^1,5

“The MB-105 Phase 1 trial has shown promising safety and efficacy signals in relapsed / refractory TCL patients. This designation further validates our development strategy as we prepare to initiate our phase 2 clinical trial in early 2025,” said Hein, in a news release.¹

REFERENCES

1. March Biosciences Receives FDA Orphan Drug Designation for MB-105, a First-in-Class CD5 CAR-T Cell Therapy, for T-Cell Lymphoma. March Biosciences. News release. January 28, 2025. Accessed January 29, 2025. https://www.globenewswire.com/news-release/2025/01/28/3016342/0/en/March-Biosciences-Receives-FDA-Orphan-Drug-Designation-for-MB-105-a-First-in-Class-CD5-CAR-T-Cell-Therapy-for-T-Cell-Lymphoma.html

2. Antitumor efficacy and safety of unedited autologous CD5.CAR T cells in relapsed/refractory mature T-cell lymphomas. NIH. News release. March 28, 2024. Accessed January 29, 2025. https://pubmed.ncbi.nlm.nih.gov/38145560/#:~:text=Despite%20newer%20targeted%20therapies%2C%20patients,syndrome%20or%20neurologic%20events%20occurred.

3. MB-105. March Biosciences. News release. Accessed January 29, 2025. https://march.bio/mb-105/

4. Autologous T-Cells Expressing a Second Generation CAR for Treatment of T-Cell Malignancies Expressing CD5 Antigen (MAGENTA). ClinicalTrials.gov. September 27, 2024. Accessed January 29, 2025. https://www.clinicaltrials.gov/study/NCT03081910

5. Antitumor efficacy and safety of unedited autologous CD5.CAR T cells in relapsed/refractory mature T-cell lymphomas. American Society of Hematology. News release. March 28, 2024. Accessed January 29, 2025. https://ashpublications.org/blood/article-abstract/143/13/1231/506723/Antitumor-efficacy-and-safety-of-unedited?redirectedFrom=fulltext