FDA names MB-101 US orphan drug for certain types of glioma
CAR T-cell therapy being developed for hard-to-treat brain cancers
The U.S. Food and Drug Administration (FDA) has granted orphan drug designation to MB-101, a CAR T-cell therapy being developed by Mustang Bio to treat certain forms of malignant glioma, a class of rare brain cancers.
Orphan drug status is given to therapies that are intended to treat, diagnose, or prevent rare diseases, defined in the U.S. as those affecting fewer than 200,000 people. This designation provides incentives to encourage companies to invest in rare disease drug development — among them, tax credits, fee waivers, and a period of market exclusivity should the treatment eventually be approved.
“We are thrilled that MB-101 received orphan drug designation,” Manuel Litchman, MD, Mustang’s CEO, said in a company press release. “This progress demonstrates our dedication to exploring new possibilities for improving outcomes in patients with challenging-to-treat cancers.”
The FDA last year had granted orphan drug status to MB-108, a virus-based therapy that Mustang is also developing for malignant glioma. The company’s ultimate goal is to use MB-101 and MB-108 together for treating these aggressive brain cancers. The combination has been dubbed MB-109.
The therapies — each delivered directly into or near a patient’s tumor — are being tested individually in Phase 1 clinical trials.
An MB-101 study (NCT02208362) was being conducted at City of Hope Medical Center in California, while an MB-108 study (NCT03657576) is underway at the University of Alabama at Birmingham. Another Phase 1b trial (NCT06614855) of MB-108 is also expected to be run at the same Alabama site.
Mustang indicated that Phase 1 studies of both therapies continue to enroll participants in these locations.
Developer aiming to test MB-101 and MB-108 together in trials
While preclinical data have demonstrated the therapeutic potential of MB-109, the two treatments have not yet been tested together in a clinical trial. Mustang noted that further development is contingent upon raising additional funds or initiating strategic partnerships.
“We hope to advance MB-101, in combination with MB-108, as a potential treatment option for patients living with malignant glioma,” Litchman said.
In particular, Mustang is studying the use of these therapies in people with aggressive gliomas where the cancer has persisted despite treatment. Litchman specifically indicated the treatment’s potential use in individuals with high-grade astrocytomas and recurrent glioblastomas. These cancers are difficult to treat and have a poor prognosis.
We hope to advance MB-101, in combination with MB-108, as a potential treatment option for patients living with malignant glioma.
MB-101 is a CAR T-cell therapy, in which immune T-cells are engineered to recognize and destroy tumor cells. T-cells have an innate ability to kill cancer cells and other threats in the body, but this approach helps them specifically target the cancerous cells.
A person’s own T-cells are removed and engineered in the lab to express a chimeric antigen receptor, or CAR, that binds to a protein called IL13Ralpha2 that’s commonly found on the surface of glioma cells. When the T-cells are returned to the body, they’re thus equipped to specifically bind to and destroy IL13Ralpha2-expressing cancer cells.
In the Phase 1 trial, the CAR T-cell therapy was tested in 65 people with recurrent or treatment-resistant high-grade glioma, most of whom had recurrent glioblastoma.
Treatment goal is to improve patient outcomes
The therapy was generally well tolerated, with half of evaluable participants achieving stable disease or better, published results showed. Among these patients were two people who achieved complete treatment responses that lasted for 7.5 months and more than five years.
Both of these individuals had high T-cell counts in their tumors before treatment, suggesting that the tumors were already more susceptible to immune attacks.
However, research has shown that tumors are very good at developing strategies to avoid immune destruction — which could limit the efficacy of CAR T-cell therapies in a broader group of patients. That’s why Mustang’s ultimate goal is to combine MB-101 with MB-108.
MB-108 is an oncolytic virus, or a virus that’s been engineered to preferentially infect and kill cancer cells while leaving the body’s healthy cells unharmed. It uses a modified version of herpes simplex virus type 1, which is the cause of oral cold sores.
The body’s immune system is also very good at going after viruses, which means the presence of MB-108 will help recruit immune cells that make tumors more vulnerable to MB-101. That’s sometimes referred to as making a so-called cold tumor hot.
“Our novel therapeutic strategy, combining our MB-101 CAR-T cell therapy with our MB-108 oncolytic virus, leverages MB-108 to reshape the tumor microenvironment … to make cold tumors ‘hot,’ thereby potentially improving the efficacy of MB-101 CAR-T cell therapy,” Litchman said.
In the ongoing Phase 1 trial, MB-108 was well tolerated in people with recurrent glioblastoma, according to Mustang.
The company had previously announced that the FDA approved the launch of a Phase 1 trial to test the MB-109 combination therapy in certain adults with recurrent glioblastoma and high-grade astrocytomas. However, there have been no updates on the launch of such a trial.
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