Orphan Drug Designation Granted to MB-106 in Waldenstrom Macroglobulinemia

The FDA has granted orphan drug designation to MB-106, Mustang Bio’s CD20-targeted autologous chimeric antigen receptor (CAR) T-cell therapy for the treatment of Waldenstrom macroglobulinemia (WM).¹

MB-106 is currently being investigated for patients with relapsed or refractory B cell non-Hodgkin lymphoma (B-NHL) in a phase 1/2 dose-escalation study (NCT03277729) being conducted at Fred Hutchinson Cancer Center. The center is collaborating on the therapy’s development. An additional clinical trial sponsored by Mustang Bio (NCT05360238) is also planned.

Data from the Fred Hutch study presented at the European Hematology Association 2022 Congress were favorable in terms of both efficacy and safety. An overall response rate (ORR) of 96% across all dose levels and indications (n=26) was achieved, including a 100% complete response rate(CRR) for patients with WM (n=2) and a 100% CRR for patients with B-NHL previously treated with CD19-directed CAR T cell therapy (n=2).

“We are very pleased to receive Orphan Drug Designation from the FDA, as it is an important regulatory milestone for Mustang’s MB-106 program for the treatment of WM, a rare B-NHL with a significant unmet medical need,” Manuel Litchman, MD, president and chief executive officer, Mustang, said in a statement.¹ “We look forward to dosing the first patient in our multicenter phase 1/2 clinical trial evaluating the safety and efficacy of MB-106 for relapsed or refractory B-NHL and chronic lymphocytic leukemia (CLL) under Mustang’s investigational new drug (IND) application shortly. In the phase 1 portion of this trial, MB-106 dose escalation will proceed in 3 separate arms, and WM patients will be included in the indolent lymphoma arm in parallel with accrual of patients to the aggressive lymphoma and CLL arms.”

The open-label, non-randomized study will be open to patients 18 years of age or older. Evidence of CD20 expression will be a requirement for inclusion in both the phase 1 and phase 2 portions. Up to 18 patients are expected to be treated in each of the 3 arms in the first phase, with 6 patients being treated at the maximum tolerated dose. Up to 71 patients will participate in each arm in phase 2. Primary end points will include incidence of treatment emergent adverse events in phase 1, the recommended phase 2 dose defined as the highest MB-106 dose in each arm that is associated with fewer than 2 cases of dose limiting toxicity in 6 patients, and the ORR for phase 2. Secondary end points will include efficacy measures such as duration of response, progression-free survival, and overall survival.

“Based on the ongoing progress, MB-106 may be a suitable outpatient treatment for these patients and another immunotherapy option for patients for whom CD19-directed CAR T cell therapy is not effective,” investigator Mazyar Shadman, MD, MPH, associate professor and physician, Fred Hutch and University of Washington, said in a separate statement.² “Enrollment in this study remains open to patients with CD20+ B-NHLs and CLL, including patients with prior CAR T treatment.”

REFERENCES

1. Mustang Bio announces orphan drug designation granted to MB-106, a CD20-targeted, autologous CAR T cell therapy for the treatment of Waldenstrom Macroglobulinemia. News release. Mustang Bio. June 22, 2022. https://finance.yahoo.com/news/mustang-bio-announces-orphan-drug-120000131.html?guccounter=1
2. Mustang Bio announces updated interim results from follicular lymphoma cohort of ongoing phase 1/2 clinical trial of MB-106, CD20-targeted CAR T therapy. News release. Mustang Bio. June 13, 2022. https://www.globenewswire.com/news-release/2022/06/13/2461188/0/en/Mustang-Bio-Announces-Updated-Interim-Results-from-Follicular-Lymphoma-Cohort-of-Ongoing-Phase-1-2-Clinical-Trial-of-MB-106-CD20-Targeted-CAR-T-Therapy.html