Servier Korea has launched Voranigo, the first IDH (isocitrate dehydrogenase) mutation-targeted therapy for low-grade glioma in Korea, opening a new treatment option for young brain tumor patients who have long faced a choice between watchful waiting and potentially toxic radiotherapy or chemotherapy.
The company held a press conference in Seoul on Tuesday to mark the domestic launch of Voranigo (vorasidenib), an oral therapy approved in Korea in January for patients aged 12 or older and weighing at least 40 kilograms with grade 2 astrocytoma or oligodendroglioma carrying an IDH1 or IDH2 mutation after surgery.
The launch is drawing attention because low-grade glioma, although relatively slow-growing, frequently recurs and can progress into a higher-grade malignancy. For many patients, the disease is diagnosed in their 30s or 40s, when they are most socially and economically active, and its burden extends beyond survival to seizures, cognitive decline, work disruption and long-term quality of life.
Professor Chang Jong-hee of Severance Hospital explains that low-grade glioma patients have long faced a treatment gap after surgery because radiotherapy and chemotherapy can cause cognitive and neurological side effects, during a press conference marking Servier Korea’s launch of Voranigo at The Plaza Seoul on Tuesday. (Credit: Servier Korea)
“For doctors treating glioma, we eventually have to tell patients that the disease will recur 100 percent,” said Professor Chang Jong-hee of the Department of Neurosurgery at Severance Hospital. “Low-grade glioma grows slowly, but it is still a malignant tumor that ultimately recurs or becomes more aggressive in many cases.”
Chang explained that the clinical challenge has been particularly difficult because surgery remains the foundation of treatment, but complete removal is often difficult due to the infiltrative nature of glioma.
After surgery, physicians have had to consider radiotherapy and chemotherapy, but these options can cause cognitive impairment and other neurological adverse effects, making treatment timing a critical issue.
“Because low-grade glioma occurs mainly among people in their 30s and 40s, when social activity is at its peak, it affects not only patients but also their families,” Chang said. “Driving restrictions, problems at work, cognitive decline, depression and anxiety all lead to a substantial deterioration in quality of life. Unlike glioblastoma, where survival is typically short, many patients with low-grade glioma live for a long time, so maintaining quality of life is very important in treatment.”
According to Chang, about 74 percent of low-grade glioma patients experience seizures, and more than half continue to have seizures even after surgery. This has often left patients in a difficult “treatment gap,” in which physicians monitor residual or recurrent tumors while postponing radiotherapy or chemotherapy to avoid long-term toxicity.
The Severance professor said that this gap has been one of the largest unmet needs in low-grade glioma care.
“Until now, even when tumors remained after surgery, we often had no choice but to observe patients because of concerns over cognitive impairment and other adverse effects from radiotherapy and chemotherapy,” he said. “Patients are most afraid of tumor progression and seizures.”
Voranigo targets mutations in IDH1 and IDH2, which are found in about 80 percent of grade 2 glioma patients and are considered key drivers of tumor development and malignant progression. The mutated IDH enzyme produces 2-hydroxyglutarate, or 2-HG, an oncometabolite associated with tumor growth.
The introduction of an IDH-targeted therapy also reflects a broader shift in brain tumor treatment toward molecularly defined precision medicine. The World Health Organization classification and major global guidelines now emphasize IDH mutation status as a core diagnostic and treatment-defining factor in glioma.
“IDH-mutant glioma has been reported to increase in size by about 10 percent every six months, and every 10 percent increase in tumor size has been associated with about a 14 percent increase in the risk of death,” Chang said. “This is why it is important to suppress IDH mutations early and slow tumor progression itself.”
He stressed that Voranigo should not be misunderstood as a treatment for all gliomas. Its indication is limited to IDH-mutant grade 2 astrocytoma and oligodendroglioma, and it does not apply to IDH-wild type glioblastoma.
“Surgical resection remains the most important standard treatment,” Chang said. “The significance of Voranigo is not that it cures the disease, but that it delays tumor progression and pushes back the timing of radiotherapy and chemotherapy as much as possible.”
Still, Chang said Voranigo does not resolve all unmet needs in brain tumor treatment, particularly for IDH-wild type glioblastoma, where treatment options remain limited.
“Even with Voranigo, there is still a tremendous unmet need,” he said. “For glioblastoma with poor prognosis, there is virtually no treatment beyond existing therapy. I hope this launch encourages further drug development in brain tumors
Professor Kim Chae-yong speaks during a press conference marking Servier Korea’s launch of Voranigo at The Plaza Seoul on Tuesday. (Credit: Servier Korea)
Professor Kim Chae-yong of the Department of Neurosurgery at Seoul National University Bundang Hospital (SNUBH) said the pivotal phase 3 INDIGO study showed that Voranigo significantly improved progression-free survival (PFS) compared with placebo, reducing the risk of disease progression or death by 65 percent.
The median PFS had not been reached in the Voranigo group, compared with 11.4 months in the placebo group.
Kim explained that the data were particularly meaningful because the study enrolled patients who had undergone surgery but had not yet received radiotherapy or chemotherapy, a population in which treatment decisions often focus on how long more toxic interventions can be safely delayed.
“Voranigo is an oral drug that crosses the blood-brain barrier and reaches tumor tissue, allowing patients to manage their disease while maintaining daily life without going back and forth to the hospital for radiotherapy,” Kim said. “The significant delay in time to next intervention means patients were able to postpone toxic chemotherapy and radiotherapy while maintaining normal social activities for longer.”
In the INDIGO study, Voranigo delayed the time to next intervention by 75 percent compared with placebo. Kim said more than 80 percent of patients remained stable without additional treatment at the two-year mark after starting therapy.
He also pointed to the drug’s effect on seizures, saying the annualized seizure rate during treatment was reduced by 64 percent compared with placebo. The therapy’s main adverse events included fatigue, musculoskeletal pain, diarrhea and seizures, but the overall tolerability profile was viewed as manageable.
“Beyond reducing the tumor growth rate, Voranigo also showed effects in reducing seizures and preserving neurocognitive function,” Kim said. “The NCCN guidelines also recommend Voranigo as a category 1 preferred option.”
Chang said the seizure data could have a direct effect on how patients live.
“The 64 percent reduction in seizure incidence confirmed in clinical research will play a decisive role in helping patients regain psychological stability and return to society,” he said.
The launch also carries symbolic importance for brain tumor drug development. Chang noted that few anticancer drugs have shown meaningful efficacy in brain tumors because many cannot adequately cross the blood-brain barrier.
“Because of the blood-brain barrier, there are very few anticancer drugs that are effective in brain tumors,” he said. “After the approval of temozolomide, a cytotoxic chemotherapy, in 2006, Voranigo is the first brain tumor treatment approved in about 20 years. It is nearly the first targeted therapy for brain tumors.”
Kim added that the drug’s arrival may encourage further development in areas where treatment options remain absent.
Lee Han-soo
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