Vorasidenib Updates: Fewer Seizures, Better Quality of Life
- There was much good news about the use of vorasidenib (brand name: Voranigo), a targeted IDH inhibitor, for patients with grade 2 gliomas at this year’s Society for Neuro-Oncology (SNO) Annual Meeting.
- Vorasidenib was FDA-approved for certain grade 2 IDH-mutant gliomas last year. This year, new data show the continued effects of vorasidenib — including a significant reduction in seizure frequency for patients and potential improvements in quality of life.
- Doctors are now carefully studying whether these treatments can help some people with grade 3 and even grade 4 tumors in the future.
- “What’s really exciting is not only what it’s doing for progression-free survival, but what’s happening for patients with reductions in seizures, and hopefully what that will mean for quality of life and cognition,” Dr. Katherine Peters, neuro-oncologist at Duke Cancer Center Brain Tumor Clinic, told SurvivorNet.
There was much good news about the use of vorasidenib (brand name: Voranigo), a targeted IDH inhibitor, for patients with grade 2 gliomas, who were previously caught in an uncomfortable treatment middle ground, at this year’s Society for Neuro-Oncology (SNO) Annual Meeting. The drug was first approved for grade 2 gliomas last year — and this year, the drug’s potential was further explored and expressed.
Grade 2 tumors were considered low-grade. They grow slowly, but relentlessly. They often affect younger adults. And they disrupt real life through seizures, memory problems, work limitations, and chronic anxiety about what comes next. Now, that balance has started to shift. Vorasidenib represents one of the most important advances in early glioma treatment in years.
“It’s really exciting that we have a smart therapy now, that isn’t just a traditional chemotherapy, something that can actually target the tumor itself,” Dr. Katherine Peters, neuro-oncologist at Duke Cancer Center Brain Tumor Clinic, told SurvivorNet during the conference.“There’s also an abstract that we have at this conference that shows really the penetration into the marketplace for vorasidenib and how it has been adopted by the community,” she said.
The new data show the continued effects of vorasidenib. There are real numbers behind it.
What Do The New Data Tell Us?
Over the past year, since FDA approval, specialists across major cancer centers have spent countless hours in tumor boards discussing who should receive this new therapy and when to introduce it.
In that time, new studies and real-world data have continued to build confidence in prescribing these drugs.
“The newer data recapitulates the old data… It tells us the old data looks real, the numbers are shaking out in the same manner, actually a little bit better, with additional clinically relevant information,” Dr. Rimas V. Lukas, neuro-oncologist at Northwestern University, told SurvivorNet. “The story is just getting more and more fleshed out, but the meat of it was always there.”
New meaningful insight from data published in Lancet also touched on seizures, which are often one of the most frightening and life-disrupting parts of living with a low-grade glioma. In the updated INDIGO analysis, patients taking vorasidenib had far fewer seizures over time than those on placebo.
“What’s really exciting is not only what it’s doing for progression-free survival, but what’s happening for patients with reductions in seizures, and hopefully what that will mean for quality of life and cognition,” Dr. Peters explained.
And for Dr. Lukas, this finding has already changed day-to-day decisions in the clinic. “When I see someone whose scans are only a little worse, but suddenly there’s a flurry of seizures, that now makes me pause and think maybe it’s time to start an IDH inhibitor,” he said, explaining that in the past, he might have simply increased anti-seizure medications instead of moving toward targeted therapy.
In the Lancet study, doctors counted how many seizures people had over time.
They found that:
- People who took vorasidenib had about 18 seizures per year
- People who took a placebo had about 51 seizures per year
That’s almost 3 times more seizures without the drug.
‘Redefining IDH-Mutant Glioma’
During the SNO Annual Meeting held in Honolulu, there was a specific session on IDH inhibitors entitled “Redefining IDH-Mutant Glioma Management: Insights Into the Modern Paradigm of Care.” During the meeting, four leading experts cited the growing number of grade 2 glioma patients now on vorasidenib for more than 5 years, with no recurrence and few to no side effects.
Most are returning to daily life and work. They also spoke a lot about the remarkably low level of toxicity associated with this drug.
“Only 3.6% of patients enrolled in ongoing treatment have had to discontinue treatment with vorasidenib due to adverse side effects, and not a single death has been associated with the treatment,” said Dr Peters.
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Vorasidenib: Beyond Grade 2
Vorasidenib opened a new chapter for glioma treatment.
The INDIGO trial helped define where this drug fits right now: early-stage, IDH-mutant grade 2 gliomas, typically one to five years after surgery, before clear contrast enhancement on MRI, and before radiation or chemotherapy has been given. That’s the space where the strongest data lives.
Doctors are now asking, “How does this change everything else we’ve been doing for decades?”
During a SurvivorNet panel, Dr. Timothy Cloughesy, neuro-oncologist at UCLA, asked how this new drug was actually changing decisions in real hospitals.
“Kate, I’m wondering when a new therapy comes in, it kind of changes the dynamic at your medical center with regard to who gets the drug, who doesn’t get the drug, how are people thinking what’s happened at your place… interactions with radiation oncology, neurosurgeons, all of that, how’s that gone?”
The honest answer is it’s still evolving.
“I’m very honest with them, of course, that we don’t have data or good robust data in grade 3 patients… I think it’s just a carefully selected patient population. We do have some data in grade 3 patients who kind of fit that category, where this could be a helpful treatment,” Dr. Kathryn Nevel, neuro-oncologist at Indiana University, said.
Some doctors are willing to consider IDH inhibitors for very select grade 3 cases — for example, tumors that were almost completely removed, not showing aggressive contrast enhancement, and sitting in less critical areas of the brain.
Addressing Treatment Uncertainty
Dr. Nevel emphasized that these decisions must be patient-centered.
“Sometimes we use things off-label. A lot of that depends on where that patient is in their life and what their perspective is on chemotherapy and radiation and everything else,” she said. “I think what’s so important about these discussions, not only between our colleagues but also the discussion with your patient … It’s more than just what we think may be the best at controlling the tumor in the immediate term. There are other factors at play, like family planning. This is a big one that comes up all the time.”
During the SNO Annual Meeting, experts cautioned that there are still unanswered questions about the drug’s effect on fertility (with no available data about potential risk to the fetus).
They encouraged the audience to be diligent with patients by reminding them of the various options, including fertility preservation (such as storage of eggs and sperm for use at a later date) or deferring attempts to conceive until treatment with an IDH inhibitor ends.
The Breakthrough: The INDIGO Trial Results
The true game-changer was the INDIGO trial, a major international study published in the New England Journal of Medicine.
The trial focused on patients with Grade 2 IDH-mutant gliomas who had already undergone surgery but had not yet received other cancer treatments like radiation or chemotherapy, making them appropriate candidates for a “watch-and-wait” approach.
Patients were randomly assigned to receive either 40 mg of oral vorasidenib once daily or a matching placebo. The primary goal was to measure progression-free survival (PFS), and the key secondary goal was the time to the next anticancer intervention (TTNI).
The results were remarkable, leading the independent monitoring committee to recommend unblinding the trial early due to the clear demonstration of efficacy.
The Key Findings:
- Progression-Free Survival: Vorasidenib significantly improved PFS. The median PFS for the vorasidenib group was 27.7 months, compared to just 11.1 months for the placebo group. This represents a hazard ratio of 0.39, meaning the risk of disease progression or death was reduced by 61% in the vorasidenib group.
- Delaying Further Treatment: Vorasidenib dramatically delayed the need for subsequent aggressive treatments. The time to the next intervention was significantly improved in the vorasidenib group, delaying the need for therapies like chemotherapy or radiation. The likelihood of being alive and not requiring further intervention by 24 months was 83.4% in the vorasidenib group, compared to only 27.0% in the placebo group.
“We know that it’s better than no treatment, but we don’t know if it’s better than other treatments,” Dr. D. Ryan Ormond, a neurosurgeon at the University of Colorado, told SurvivorNet in a previous talk.
However, he also acknowledged the strength of the INDIGO data.
“We have progression-free survival data from that trial. We don’t have life expectancy data from that trial, and we’re not going to get real life expectancy data from that trial because patients getting a placebo were allowed to cross over at progression. So in the end, every patient got vorasidenib if they wanted it at some point in the time of the study,” he added.
