FDA Grants Orphan Drug Designation to MB-108 Oncolytic Virus for Malignant Glioma
核心洞察
The FDA has granted Orphan Drug Designation to MB-108, an oncolytic virus, for treating malignant glioma (搜索), offering potential market exclusivity for Mustang Bio (搜索).
MB-108 is currently in a phase 1 trial at City of Hope for recurrent glioblastoma (搜索), demonstrating activity and tolerability in patients.
A combination therapy, MB-109, which includes MB-108 and MB-101 CAR T-cell therapy, is being developed to enhance tumor immunogenicity and CAR T-cell efficacy.
Mustang Bio (搜索)'s MB-108, a second-generation herpes simplex virus type 1 (HSV-1) oncolytic virus, has received Orphan Drug Designation (ODD) from the FDA for the treatment of malignant glioma (搜索). This designation aims to support the development of therapies for rare diseases, offering potential market exclusivity and other benefits to Mustang Bio. The development of MB-108 represents a promising avenue for patients with limited treatment options and historically poor prognoses.
Clinical Development of MB-108
MB-108 is currently being investigated in a phase 1 clinical trial (NCT03657576) at City of Hope for patients with recurrent glioblastoma (搜索). Early results from this trial indicate that MB-108 is active and well-tolerated in this patient population. The ongoing study aims to further evaluate the safety and efficacy of MB-108 as a monotherapy.
MB-109: A Novel Combination Therapy
Mustang Bio (搜索) is also developing MB-109, a combination therapy that includes MB-108 and MB-101, an IL13Rα2 (搜索)-targeted CAR T-cell therapy. The rationale behind this combination is to leverage MB-108's ability to induce an inflamed tumor microenvironment, potentially enhancing the infiltration and activity of MB-101 CAR T-cells. Preclinical data presented at the 2022 AACR Annual Meeting support the addition of MB-108 to MB-101 to improve the efficacy of CAR T-cell therapy in recurrent glioblastoma (搜索). The FDA accepted an investigational new drug application for MB-109 in October 2023, and it is currently being evaluated in a phase 1 trial for patients with IL13Rα2-positive relapsed or refractory glioblastoma and anaplastic astrocytoma (搜索).
Prior Clinical Experience with MB-101 and MB-108
Data from separate phase 1 studies of MB-101 (NCT02208362) and MB-108 have previously demonstrated that both therapies are well-tolerated in patients with recurrent glioblastoma (搜索) multiforme. Notably, in the MB-101 study, two patients with high levels of intratumoral CD3-positive T cells prior to treatment (indicating "hot" tumors) 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 phase 1 study, suggesting that pre-existing immune infiltration may predict response to MB-101.
Strategic Implications and Future Directions
According to Manuel Litchman, MD, president and chief executive officer of Mustang Bio (搜索), Inc., the ODD for MB-108 could provide additional market exclusivity. Mustang Bio aims to advance MB-108, in combination with MB-101, as a potential treatment option for patients living with malignant glioma (搜索), including those with recurrent glioblastoma (搜索) and high-grade astrocytomas. The company plans to request ODD from the FDA for MB-101 in malignant gliomas as well. Further development of the MB-109 program for recurrent glioblastoma and high-grade astrocytomas is contingent upon raising additional funding and/or consummating a strategic partnership.