FDA Approves Vorasidenib for Treating IDH-Mutant Glioma

The U.S. Food and Drug Administration (FDA) has recently approved a new drug that is effective for treating IDH-mutant low-grade glioma (a type of brain cancer). This new drug was developed in 2008 at the Johns Hopkins Kimmel Cancer Center. 

This drug is known as vorasidenib. It is a cancer treatment that targets a mutated gene called IDH. It inhibits its activity and reduces cancer growth. This gene was first identified by Bert Vogelstein and his team at Johns Hopkins Kimmel Cancer Center’s Ludwig Center in 2008. They created the most comprehensive genetic analysis for brain cancer that evaluated all protein-encoding genes that were known. 

Researchers discovered that the IDH gene was previously unknown to be linked to any tumor type. But it was frequently mutated in a specific group of brain cancers. 

One of the experts said that the IDH gene is a key component in cancer genome sequencing and this highlights the importance of basic research. He also said that understanding more about a disease can help experts develop better treatments.  

Vogelstein’s genetic discoveries have led to precision cancer medicine that focuses on therapies tailored to each patient’s unique genetic makeup. 

A phase 3 clinical trial that was published in the New England Journal of Medicine in June 2023 found that the vorasidenib drug effectively improved progression-free survival in patients with grade 2 IDH-mutant glioma. It also delayed the time of the next intervention as compared to patients who took placebo. This trial was sponsored by Servier- the international pharmaceutical company that brought the vorasidenib drug to market. 

This FDA-approved drug and the discovery of the IDH gene have led to a new classification of gliomas. They classify cancers with an IDH mutation from aggressive ones without an IDH mutation, including glioblastoma. It is the most common primary brain cancer in adults.  

The National Cancer Institute reports that 80% of low-grade gliomas, IDH-mutant astrocytoma and oligodendroglioma are commonly found in younger adults. They also report that these cancers are associated with slower growth and longer survival compared to aggressive high-grade gliomas. 

There are some treatments for these cancers such as surgery to remove tumors, followed by radiation and chemotherapy to attack the remaining cells. In some cases, adding an IDH inhibitor can also delay radiation therapy and chemotherapy. 

Matthias Holdhoff, co-director of the Johns Hopkins Kimmel Cancer Center brain tumor program and co-investigator on the 2023 clinical trial, thinks that delaying radiation therapy and chemotherapy with a drug can be beneficial for patients with slow-growing IDH-mutant gliomas. This will potentially offer a new standard of care.