Virus-based MB-108 named FDA orphan drug for malignant glioma
Mustang Bio's cancer-infecting virus to be used with its CAR T-cell therapy
The U.S. Food and Drug Administration (FDA) has granted orphan drug designation to MB-108, an experimental virus-based therapy that Mustang Bio is developing for malignant glioma, a type of brain cancer.
The FDA gives this designation to experimental therapies for rare conditions, which are defined as diseases that affect fewer than 200,000 people in the U.S. The designation is to help incentivize companies to invest in developing new treatments for rare diseases. Among other benefits, orphan drugs are guaranteed seven years of market exclusivity if they are ultimately approved by the FDA.
“The Orphan Drug Designation for MB-108 is significant for Mustang, as it could provide additional market exclusivity,” Manuel Litchman, MD, president and CEO of Mustang, said in a company press release.
Virus that’s been engineered to preferentially infect and kill cancer cells
MB-108 (also known as C134) is an oncolytic virus, meaning it’s a virus that’s been engineered so it will preferentially infect and kill cancer cells, without harming healthy cells. MB-108 uses a modified version of herpes simplex virus type 1, a virus that can cause genital herpes as well as cold sores.
Mustang is developing MB-108 to be used in combination with MB-101, the company’s investigational CAR T-cell therapy. CAR T-cell therapies work by engineering T-cells, a type of immune cell, with a human-made protein called a chimeric antigen receptor, or CAR. The CAR directs the T-cells to attack other cells that express a particular protein marker.
In the case of MB-101, the T-cells are engineered with a CAR targeting IL-13Ralpha2, a protein that’s commonly expressed by glioma cells. Mustang said it is planning to ask the FDA to also grant MB-101 an orphan drug designation as a potential treatment for malignant glioma.
CAR T-cell treatments have shown promising results for some cancers, but they aren’t effective for every individual. One of the biggest stumbling blocks for the therapies is that tumors tend to have mechanisms to avoid destruction by the immune system.
However, the immune system is generally very good at going after viruses, which is where MB-108 comes in. The idea is to use the virus not only to kill cancer cells, but also to make the tumor more vulnerable to the CAR T-cell therapy MB-101 (sometimes referred to as turning a cold tumor “hot”). The combination of MB-101 and MB-108 is designated MB-109.
‘Potential treatment option for patients living with malignant glioma’
“We hope to advance MB-108, in combination with MB-101, as a potential treatment option for patients living with malignant glioma, including patients with recurrent glioblastoma (“GBM”) and high-grade astrocytomas, where there is historically a median overall survival of six months,” Litchman said. “Our novel therapeutic strategy, combining our MB-108 oncolytic virus with MB-101 CAR-T cell therapy, could be the first-ever industry-sponsored trial of its kind for the treatment of malignant glioma.”
Both MB-101 and MB-108 are currently being tested for malignant glioma in two separate Phase 1 clinical trials. The MB-101 trial (NCT02208362) is ongoing at City of Hope Medical Center in California, while the MB-108 trial (NCT03657576) is being conducted at the University of Alabama at Birmingham.
Early data from the MB-101 trial suggested the CAR T-cell treatment alone led to complete responses in two individuals who had high counts of T-cells already in their tumors, suggesting that those tumors were more susceptible to immune attack. This finding supports the idea that using MB-108 to increase tumor susceptibility to the CAR T-cell therapy may be an effective strategy, according to Mustang.
“These advancements highlight our dedication to potentially improving outcomes for patients battling difficult-to-treat cancers,” Litchman said.
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