FDA Grants Orphan Drug Status to MB-101 for Glioblastoma, Astrocytomas

The U.S. Food and Drug Administration (FDA) has granted orphan drug designation to Mustang for MB-101 (IL13Ra2-targeted CAR T-cells) for the treatment of recurrent diffuse and astrocytomas (anaplastic astrocytoma) and glioblastoma (GBM), according to a news release from Mustang Bio.

The FDA grants orphan drug designation to treatments developed for rare diseases — those affecting fewer than 200,000 people in the U.S.

As previously reported, preclinical data presented at the American Association for Cancer Research Annual Meeting in 2022 supported the potential of combining MB-108 with MB-101 to enhance outcomes for patients with recurrent glioblastoma. MB-108, an oncolytic virus, is designed to modify the tumor microenvironment (TME) by converting cold tumors — those that evade immune detection — into hot tumors that attract immune activity. This process may help increase the effectiveness of MB-101.

Additionally, separate early-phase data from City of Hope and the University of Alabama at Birmingham have shown that MB-101 and MB-108 were both well tolerated in patients with recurrent glioblastoma. In a 2024 Nature Medicine paper from City of Hope, two patients with high levels of intratumoral CD3+ T cells — classified as having hot tumors — experienced complete responses after receiving MB-101 alone, lasting 7.5 months and more than 66 months, respectively. These two patients were among just three in the study with the highest pre-treatment immune activity, as per the release.

Both phase 1 trials — MB-101 at City of Hope and MB-108 at the University of Alabama at Birmingham — remain open and continue to enroll patients.

According to the National Cancer Institute, cold tumors describe a tumor that does not trigger a strong immune response. These tumors are often surrounded by cells that block immune activity, preventing T-cells from attacking the tumor. Cold tumors usually resist immunotherapy.

Furthermore, hot tumors describe a tumor that triggers a strong immune response. These tumors often display surface markers that help T-cells recognize and attack them. Hot tumors are more likely to respond to immunotherapy.

“We are thrilled that MB-101 received orphan drug designation on time and with a designation that is broader than the indication proposed,” Dr. Manuel Litchman, president and chief executive officer of Mustang Bio, said in the news release. “The orphan drug designation for MB-101, coupled with the orphan drug designation granted previously for MB-108, is strong validation for our science, as we hope to advance MB-101, in combination with MB-108, as a potential treatment option for patients living with malignant glioma, including patients with recurrent GBM and high-grade astrocytomas.

Litchman continued, “This progress demonstrates our dedication to exploring new possibilities for improving outcomes in patients with challenging-to-treat cancers.”

The future development of the MB-109 program for recurrent glioblastoma and high-grade astrocytomas will depend on securing additional funding or entering a strategic partnership.

This designation is meant to encourage research and development in areas where there may be limited options for patients. It comes with benefits like tax credits to help offset clinical trial costs and waivers for certain FDA fees. If the drug is eventually approved, it may also receive seven years of market exclusivity for that rare condition, which helps protect access to the treatment regardless of patent status.

Reference:

“Mustang Bio Granted Orphan Drug Designation by U.S. FDA for MB-101 (IL13Ra2-targeted CAR T-cells) to Treat Astrocytomas and Glioblastoma,” Mustang Bio, Inc., GlobeNewswire, July 7, 2025.

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