Vorasidenib is approved by the U.S. Food and Drug Administration (FDA) for patients with grade 2 gliomas with IDH1 or IDH2 mutations.
Based on evidence from the INDIGO clinical trial, a global Phase 3, double-blind, randomized clinical trial, vorasidenib more than doubled progression-free survival and delayed the need for treatment with radiation and chemotherapy for patients. with grade 2 IDH mutant glioma after surgery to remove the tumor. INDIGO was the first Phase 3 clinical trial of a molecularly targeted therapy for IDH mutant glioma.
The INDIGO study shows that IDH inhibitors can work in low-grade gliomas with the IDH mutation. The last drug approved for low-grade gliomas was in 1999, so this will be the first new drug in a long time.”
Patrick Y. Wen, MD, director of the Center for Neuro-Oncology at Dana-Farber Cancer Institute and one of the study’s three chairs
Grade 2 gliomas are incurable brain tumors. IDH mutations are found in the vast majority of lower grade gliomas.
An important advantage of treatment with vorasidenib is that it can delay the need for treatment with radiation and chemotherapy. Current treatment involves surgery followed by radiation and chemotherapy. Radiation and chemotherapy are effective treatments, but after many years of treatment, patients will experience signs of cognitive impairment that normally occur in much older people.
“These patients are often young, somewhere in their thirties or forties. But ten to twenty years later, even if they are doing well from the tumor tip, they often show signs of dementia after radiation and chemotherapy,” says Wen. “If this drug can delay the initiation of these treatments, it would delay cognitive impairment in patients and preserve their quality of life.”
The INDIGO study enrolled 331 patients with grade 2 IDH mutated gliomas who had undergone surgery to remove the tumor. Patients who enrolled did not require immediate radiation and chemotherapy and were instead in a watch-and-wait period. During this period they were randomized to use vorasidenib or placebo.
Patients taking vorasidenib had a median of 27.7 months of progression-free survival compared to 11.1 months for patients taking a placebo. The time to next treatment for patients taking the placebo was 17.8 months. For those taking vorasidenib, a median was not determined in the most recent analysis, as only 11.3% of these patients had progressed to the next treatment to date. The drug also had a manageable safety profile.
“The study showed no difference in quality of life compared to placebo,” says Wen. “Tolerability is important because this is a drug that we expect people to take for years.”
The approval opens the door to several new options for patients. For example, Wen has an ongoing trial of vorasidenib with immunotherapy and planned trials combining vorasidenib with standard radiotherapy and chemotherapy.
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