FDA Grants Orphan Drug Designation to Mustang Bio's MB-108 for Malignant Glioma
核心洞察
The FDA has granted Orphan Drug Designation to MB-108, a second-generation herpes simplex virus type 1 oncolytic virus, for treating malignant glioma (搜索).
MB-108 is being investigated in a phase 1 trial for recurrent glioblastoma (搜索) at City of Hope, demonstrating activity and tolerability.
MB-108 is also part of a novel combination regimen, MB-109, with MB-101 CAR T-cell therapy, designed to improve CAR T-cell therapy efficacy.
Mustang Bio (搜索), Inc. has received Orphan Drug Designation (ODD) from the FDA for MB-108, a second-generation herpes simplex virus type 1 (HSV-1) oncolytic virus, for the treatment of malignant glioma (搜索). This designation aims to support the development of MB-108, particularly in combination with MB-101 CAR T-cell therapy, for patients with recurrent glioblastoma (搜索) and high-grade astrocytomas (搜索), where the median overall survival is historically poor.
Clinical Development of MB-108 and MB-109
MB-108 is currently under evaluation in an ongoing phase 1 trial (NCT03657576) at City of Hope for patients with recurrent glioblastoma (搜索), where it has shown promising activity and tolerability. Preclinical data presented at the 2022 AACR Annual Meeting support the combination of MB-108 with the IL13Rα2 (搜索)-targeted CAR T-cell therapy MB-101, forming the novel regimen MB-109. This combination seeks to convert immunologically "cold" tumors into "hot" tumors, potentially enhancing the efficacy of MB-101 CAR T-cell therapy.
Rationale for MB-108 and MB-101 Combination
The therapeutic strategy behind MB-109 involves the initial injection of MB-108 into tumor cells to infect them, which subsequently recruits endogenous CD8- and CD3-positive effector T-cells. This process aims to create an inflamed tumor microenvironment, facilitating the infiltration, activation, and tumor-killing activity of the injected MB-101 CAR T cells.
Prior Clinical Data
Previously reported data from separate phase 1 studies of MB-101 (NCT02208362) and MB-108 have indicated that both therapies were well-tolerated in patients with recurrent glioblastoma (搜索) multiforme. Notably, two patients with high levels of intratumoral CD3-positive T cells prior to treatment (indicating "hot" tumors) who received MB-101 alone achieved complete responses lasting 7.5 and more than 31 months, respectively. These patients exhibited the highest pre-treatment tumor activity among all 53 patients treated in the MB-101 phase 1 study.
Regulatory and Strategic Considerations
In October 2023, the FDA accepted an investigational new drug (IND) application for MB-109 for the treatment of patients with IL13Rα2 (搜索)-positive relapsed or refractory glioblastoma (搜索) and anaplastic astrocytoma. The combination is currently being evaluated in a phase 1 trial. However, Mustang Bio (搜索) has noted that further development of the MB-109 program for recurrent glioblastoma and high-grade astrocytomas (搜索) is contingent upon securing additional funding and/or establishing a strategic partnership.
Executive Commentary
Manuel Litchman, MD, president and chief executive officer of Mustang Bio (搜索), Inc., stated, "The ODD 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 (搜索), including patients with recurrent glioblastoma (搜索) and high-grade astrocytomas (搜索), where there is historically a median overall survival of six months."
Litchman added, "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 (搜索). As such, Mustang plans to also request ODD from the FDA for MB-101 [IL13Rα2 (搜索)-targeted CAR T-cell therapy] in malignant gliomas. These advancements highlight our dedication to potentially improving outcomes for patients battling difficult-to-treat cancers."