Targeted glioma therapy…'Voranigo' launches in Korea

Therapy targeting mutant IDH…possibility of delaying treatment intervention, such as radiation and cancer therapy

Has improved primary endpoints compared with placebo …expected to improve the quality of life

The possibility of a shift in treatment strategies is likely in the field of low-grade glioma (LGG) treatment as the first therapy targeting IDH mutations makes its debut in South Korea.

Given the nature of the disease, which repeatedly recurs after surgery and eventually progresses to a high-grade, it is drawing attention as a new option to supplement the limitations of existing radiation and chemotherapy-centered treatments. In particular, it is considered highly significant because it can reduce the burden of cognitive decline and deterioration in quality of life by delaying the timing of toxic radiation and chemotherapy.

On the 12th, Servier Korea held a press conference at the Plaza Hotel in Jung-gu, Seoul, to commemorate the domestic launch of Voranigo (vorasidenib). Voranigo was previously granted domestic approval as a glioma treatment this past January.

With this approval, Voranigo can now be used for adolescent and adult glioma patients aged 12 and older weighing at least 40 kg, specifically those with Grade 2 astrocytoma or oligodendroglioma harboring an IDH1 or IDH2 mutation.

Low-grade glioma is a brain tumor that grows relatively slowly but carries a high risk of recurrence and can progress into high-grade malignant tumors over time. It is mainly discovered through seizure symptoms, and surgical resection has traditionally been utilized as the standard treatment.

Professor Jong Hee Chang, a professor of Neurosurgery at Severance Hospital

However, medical staff explain that a treatment gap has existed because complete resection is often difficult, and the subsequent radiation therapy and chemotherapy also carry a heavy burden of cognitive decline or neurological adverse reactions.

Professor Jong Hee Chang, a professor of Neurosurgery at Severance Hospital, explained, "Low-grade glioma is difficult to cure, so it often eventually recurs or progresses to high-grade glioma," and added, "Existing standard treatments made it difficult to remove lesions completely, and radiation and chemotherapy performed after surgery also had limitations due to side effects such as cognitive impairment."

Professor Chang continued, "Voranigo is the first new brain tumor treatment to be approved since temozolomide was approved for glioblastoma in 2006," and evaluated that "The emergence of Voranigo is very significant in that most drugs have failed development in the past because they could not sufficiently pass through the blood-brain barrier (BBB)."

Voranigo is an oral treatment that directly targets IDH1 and 2 mutations. IDH mutations are known to be key biomarkers identified in approximately 80% of Grade 2 glioma patients. Currently, the World Health Organization (WHO) and the National Comprehensive Cancer Network (NCCN) also present IDH mutations as major diagnostic criteria and recommend testing.

The basis for approval is the global Phase 3 INDIGO study. This study was conducted on patients with low-grade IDH-mutant glioma who had not yet undergone radiation or chemotherapy after surgery.

Professor Kim Jae-yong, a professor of Neurosurgery at Seoul National University Bundang Hospital

The study results showed that Voranigo reduced the risk of disease progression or death by 65% compared to the placebo. The median progression-free survival (PFS) was 11.4 months in the placebo group, whereas the Voranigo group did not reach the median.

In addition, the time to next treatment intervention (TTNI) was significantly delayed. The incidence of seizures during annual treatment with Voranigo decreased by 64% compared to the placebo.

In terms of safety, fatigue, musculoskeletal pain, diarrhea, and seizures were reported as major adverse reactions, but the overall tolerability level was favorable. The results of the study were published in the New England Journal of Medicine (NEJM) and were also presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.

Medical staff cited the delay of treatment intervention as the greatest significance of Voranigo. It is believed that delaying the timing of relatively toxic radiation and chemotherapy increases the likelihood of maintaining the patient's quality of life.

Kim Jae-yong, a professor of Neurosurgery at Seoul National University Bundang Hospital, said, "Voranigo showed a result of delaying the time to the next treatment intervention by 75% in clinical studies," and added, "This is significant in that it practically secured a period during which patients can maintain a normal social life by delaying the timing of highly toxic chemotherapy and radiation therapy."