close
close

FDA grants MB-108 orphan drug designation for malignant glioma

The FDA has granted second-generation oncolytic herpes simplex virus type 1 (HSV-1) MB-108 orphan drug designation (ODD) for the treatment of patients with malignant glioma.1

MB-108 is being evaluated for the treatment of patients with recurrent glioblastoma in an ongoing Phase 1 study (NCT03657576) at City of Hope, where it has been shown to be active and well tolerated.

Additionally, preclinical data previously reported at the 2022 AACR Annual Meeting support the addition of MB-108 to the novel IL13Rα2-targeted CAR T-cell therapy MB-101 for patients with recurrent glioblastoma. This combination regimen, MB-109, is designed to make cold tumors “hot” and potentially improve the effectiveness of MB-101 CAR T cell therapy.

Previously published data from separate phase 1 trials of MB-101 (NCT02208362) and MB-108 showed that these therapies were well tolerated in patients with recurrent glioblastoma multiforme. Of note, two patients with high pretreatment intratumoral CD3-positive T cells (indicative of “hot” tumors) who received MB-101 alone achieved a complete response of 7.5 and more than 31 months, respectively. These patients had the highest pretreatment tumor activity among all 53 patients treated in this phase 1 study.

Both Phase 1 clinical trials for MB-101 and MB-108 are underway at City of Hope and the University of Alabama at Birmingham, respectively.

“The ODD for MB-108 is significant for Mustang as it could provide additional market exclusivity. [We] We hope to advance MB-108 in combination with MB-101 as a potential treatment option for patients with malignant glioma, including patients with recurrent glioblastoma and high-grade astrocytomas, which historically have a median overall survival of six months.” Manuel Litchman, MD, President and CEO of Mustang Bio, Inc. stated in a press release.

When MB-109 is administered, MB-108 is first injected into the tumor cells to infect them, resulting in the recruitment of endogenous CD8 and CD3 positive effector T cells. These T cells lead to an inflamed tumor microenvironment, which may allow the injected MB-101 CAR T cells to better penetrate into and through the tumor mass, become activated, and promote tumor cell killing.

In October 2023, the FDA accepted an investigational new drug application for MB-109 for the treatment of patients with IL13Rα2-positive relapsed or refractory glioblastoma and anaplastic astrocytoma.2 The combination is being evaluated for this patient population in a phase 1 study.3

The company also noted that further development of the MB-109 program for recurrent glioblastoma and high-grade astrocytomas is contingent on obtaining additional funding and/or entering into a strategic partnership.1

“Our novel therapeutic strategy, combining our oncolytic virus MB-108 with the CAR T-cell therapy MB-101, may be the first industry-sponsored study of its kind for the treatment of malignant gliomas. Therefore, Mustang plans to also apply to the FDA for ODD for MB-101 [IL13Rα2‐targeted CAR T-cell therapy] in malignant gliomas,” Litchman continued. “These advances underscore our commitment to potentially improving outcomes for patients battling difficult-to-treat cancers.”

  1. Mustang Bio has received orphan drug designation from the US FDA for MB-108 (HSV-1 oncolytic virus) for the treatment of malignant gliomas. Press release. Mustang Bio. November 7, 2024. Accessed November 7, 2024. https://ir.mustangbio.com/news-events/press-releases/detail/184/mustang-bio-granted-orphan-drug-designation-by-us- fda -for
  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. Press release. Mustang Bio, Inc. October 26, 2023. Accessed November 7, 2024. https://ir.mustangbio.com/news-events/press-releases/detail/168/mustang-bio-announces-fda-acceptance-of – ind application for
  3. Mustang Bio announces a Phase 1 clinical trial combining MB-101 (IL13Rα2-targeted CAR T-cell therapy) and MB-108 (C134 oncolytic virus) for the treatment of glioblastoma. Press release. Mustang Bio. April 13, 2022. Accessed November 7, 2024.

You may also like...