MB-108 Receives FDA Orphan Drug Designation for Malignant Glioma
核心洞察
The FDA has granted Orphan Drug Designation to Mustang Bio (搜索)'s MB-108 for treating malignant glioma (搜索), offering benefits like tax credits and market exclusivity.
MB-108, a second-generation herpes simplex virus type 1 (HSV-1) oncolytic virus, is currently being evaluated in a phase 1 trial for recurrent glioblastoma (搜索).
Preclinical data suggests combining MB-108 with MB-101 CAR T-cell therapy (MB-109) could enhance treatment efficacy by converting 'cold' tumors to 'hot' tumors.
Mustang Bio (搜索)'s MB-108, a second-generation herpes simplex virus type 1 (HSV-1) oncolytic virus, has been granted Orphan Drug Designation (ODD) by the FDA for the treatment of malignant glioma (搜索). This designation aims to support the development of therapies for rare diseases affecting fewer than 200,000 people in the U.S. and offers benefits such as tax credits for clinical trial costs, prescription drug user fee waivers, and seven years of market exclusivity upon approval.
Clinical Development of MB-108
MB-108 is currently under evaluation in an ongoing phase 1 clinical trial (NCT03657576) at City of Hope for the treatment of recurrent glioblastoma (搜索). Early results from the trial indicate that MB-108 is 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," said Manuel Litchman, MD, president and chief executive officer of Mustang Bio (搜索), Inc. He further added, "[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, where there is historically a median overall survival of 6 months."
Combination Therapy: MB-109
Preclinical data presented at the 2022 American Association for Cancer Research (AACR) Annual Meeting highlighted the potential of combining MB-108 with MB-101, a chimeric antigen receptor (CAR) T-cell therapy targeting IL13Rα2 (搜索) in recurrent glioblastoma (搜索). This combination, known as MB-109, aims to transform immunologically "cold" tumors into "hot" tumors, potentially enhancing the effectiveness of MB-101 CAR T-cell therapy. In the phase 1 trial of MB-101 (NCT02208362), two patients with high tumor immune activity prior to treatment achieved complete responses lasting 7.5 months and over 31 months, respectively.
Ongoing and Planned Studies
Both 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. A phase 1 study of MB-109 is planned to evaluate its safety, tolerability, and efficacy in patients with recurrent GBM and high-grade astrocytoma (搜索), with enrollment expected to begin in 2024.
Mechanism of Action for MB-109
MB-109 combines MB-101, the IL13Rα2 (搜索)-targeted CAR T-cell therapy, with MB-108, the HSV-1 oncolytic virus. The oncolytic virus is injected directly into tumor cells, infecting them and recruiting CD8- and CD3-positive T cells. This process creates an inflamed tumor microenvironment, potentially allowing MB-101 CAR T cells to penetrate deeper into the tumor, activate more effectively, and enhance their ability to destroy cancer cells.
In October 2023, the FDA accepted an investigational new drug (IND) application for MB-109 in IL13Rα2 (搜索)-positive relapsed or refractory glioblastoma (搜索) and anaplastic astrocytoma. Continued development of the MB-109 program is contingent upon raising additional funding and/or consummating a strategic partnership.