MB-108 Gains FDA Orphan Drug Status for Malignant Glioma Treatment
MB-108 shows activity and is well tolerated in recurrent glioblastoma, with preclinical data supporting its combination with MB-101 CAR T-cell therapy for improved outcomes.
- The FDA granted orphan drug designation (ODD) to MB-108 for the treatment of patients with malignant glioma.
- MB-108 is a second-generation herpes simplex virus type 1 (HSV-1) oncolytic virus.
- An ongoing phase 1 trial (NCT03657576) is currently evaluating MB-108 for the treatment of recurrent glioblastoma.
MB-108, a second-generation HSV-1 oncolytic virus, has been granted ODD from the FDA for the potential treatment of patients with malignant glioma.1
The FDA awards ODD to drugs and biologics aimed at safely and effectively treating, diagnosing, or preventing rare diseases or conditions affecting fewer than 200,000 people in the US. This designation offers specific benefits, including tax credits for clinical trial costs and waivers for prescription drug user fees. Products granted ODD status by the FDA also gain 7 years of market exclusivity for the designated disease, which is separate from any intellectual property rights.
A phase 1 trial is ongoing to evaluate MB-108 in malignant glioma at City of Hope. The trial has already shown the agent to be active and well tolerated in this patient population.
“The orphan drug designation for MB-108 is significant for Mustang, as it could provide additional market exclusivity. [We] hope to advance MB-108, in combination with MB-101, as a potential treatment option for patients living with malignant glioma, including patients with recurrent glioblastoma and high-grade astrocytomas, where there is historically a median overall survival of 6 months,” Manuel Litchman, MD, president and chief executive officer of Mustang Bio, Inc., stated in a press release.
3D illustration of brain anatomy: © PIC4U - stock.adobe.com
Preclinical data on MB-108 were previously reported at the 2022 American Association for Cancer Research Annual Meeting and highlighted the potential benefits of adding MB-108 to an innovative chimeric antigen receptor (CAR) T-cell therapy, MB-101, designed to target IL13Rα2 in patients with recurrent glioblastoma. This new combination approach, known as MB-109, aims to turn "cold" tumors into "hot" ones, possibly increasing the effectiveness of MB-101 CAR T-cell therapy.
In early clinical studies, both MB-101 and MB-108 were well tolerated by patients with recurrent glioblastoma multiforme. In the phase 1 trial of MB-101 (NCT02208362), 2 patients with high tumor immune activity prior to treatment achieved complete responses. These responses lasted 7.5 months and more than 31 months, respectively, marking notable outcomes in this patient population.
Both of these phase 1 trials evaluating MB-101 and MB-108 are ongoing at City of Hope and the University of Alabama at Birmingham and continue to enroll patients. Additionally, a planned phase 1 study of MB-109 will evaluate the safety, tolerability, and efficacy of MB-109 in patients with recurrent GBM and high-grade astrocytoma. The study is expected to begin enrolling patients in 2024.
“Our novel therapeutic strategy, combining our MB-108 oncolytic virus with MB-101 CAR T-cell therapy, could be the first-ever industry-sponsored trial of its kind for the treatment of malignant glioma. As such, Mustang plans to also request ODD from the FDA for MB-101 [IL13Rα2‐targeted CAR T-cell therapy] in malignant gliomas,” Litchman continued. “These advancements highlight our dedication to potentially improving outcomes for patients battling difficult-to-treat cancers.”
About MB-109
MB-109 combines MB-101, the IL13Rα2‐targeted CAR T-cell therapy licensed from City of Hope, with MB-108, the HSV-1 oncolytic virus licensed from Nationwide Children’s Hospital.
When MB-109 is administered, MB-108 is first injected directly into the tumor cells to infect them. It works by infecting them and recruiting the body’s own CD8- and CD3-positive T cells. This process creates an inflamed tumor environment, which may allow the MB-101 CAR T cells, once injected, to penetrate deeper into the tumor, activate more effectively, and enhance their ability to destroy cancer cells.
Previously, in October 2023, the FDA accepted an investigational new drug application for MB-109 in IL13Rα2-positive relapsed or refractory glioblastoma and anaplastic astrocytoma.2
MB-109 is currently being evaluated in a phase 1 trial. Additionally, continued development of the MB-109 program is ongoing for the potential treatment of recurrent glioblastoma and high-grade astrocytomas and is contingent upon raising additional funding and/or consummating a strategic partnership, according to the press release.1
REFERENCES:
1. Mustang Bio granted orphan drug designation by US FDA for MB-108 (HSV-1 oncolytic virus) to treat malignant glioma. News release. Mustang Bio. November 7, 2024. Accessed November 8, 2024. https://tinyurl.com/2srbr2fv
2. Mustang Bio announces FDA acceptance of IND application for MB-109, a novel combination of MB-101 (IL13Rα2‐targeted CAR-T cell therapy) and MB-108 (HSV-1 oncolytic virus), for the treatment of recurrent glioblastoma and high-grade astrocytoma. News release. Mustang Bio, Inc. October 26, 2023. Accessed November 8, 2024. https://tinyurl.com/4z2rmv5z
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