Voranigo (vorasidenib) for adult and pediatric patients 12 years and older with grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation

Transcript

My name is Kirollos Hanna and I'm the director of pharmacy with Minnesota Oncology. I'm excited to speak with you all today about the role of vorasidenib in the treatment of patients with astrocytomas or oligodendrogliomas. In August of 2024 this year, the FDA did approve vorasidenib. It was based on the INDIGO study in this particular patient population. So it is important to highlight that this drug is approved in adult patients, or pediatric patients who are 12 years of age and older, who have an IDH1 or an IDH2 mutation in patients that also have a grade II astrocytoma or oligodendroglioma with these suspected mutations by an FDA approved test. It is important to also highlight that this treatment should follow surgery, including biopsy or a subtotal resection, or even a gross total resection.

The dosing of vorasidenib in this population, in the adult population, it is 40 mg orally once daily. In the pediatric population, again, that's as young as 12 years of age, we have to make sure we're looking at this patient's weight. If they're 40 kg or above, they receive the same dosing as the adult patient, which was 40 mg once daily. If they are below 40 kg, it's important that they take this medication at 20 mg once daily. Now, the product does not matter if it's taken with or without food, so we do have that flexibility in our patients.

Before we get into the clinical trial that established the role of this particular therapeutic in this population, it is important to highlight that astrocytomas and oligodendrogliomas, these are neurological brain tumors that stem from those particular cell lines. The presence of an IDH1 or an IDH2 mutation generally in either of these tumors can be as high of a prevalence as 80 to 90%. The astrocytoma aspect, if you have a low-grade glioma, for example, it does tend to be slightly lower expression, but for the most part, the high-grade neuro cancers such as these do have pretty high IDH1 or IDH2 expression.

Focusing a little bit on the clinical trial, looking at the INDIGO study, this did look at 331 patients that had these grade II astrocytomas or oligodendrogliomas, had also the IDH1 or 2 mutations, and these patients were enrolled following surgery. This was a randomized multi-center double-blind study, and it was placebo controlled, as historically, this patient population really does not have a widely accepted standard of care. The patients were randomized in a one-to-one fashion. They received vorasidenib 40 mg PO once daily, or placebo, and patients were on therapy until progressive disease or unacceptable toxicity. These patients who were randomized to placebo could have also crossed over to the vorasidenib group if there was any type of incidents of disease progression.

When we look at the major efficacy endpoint of the INDIGO study, they did look at progression-free survival, but they also looked at the time to next intervention. What was the duration of response and how long could patients be on therapy without requiring a subsequent intervention? As it relates to the progression-free survival, the hazard ratio for the PFS was 0.39, demonstrating a 61% relative risk reduction in the likelihood of progression or death, favoring the patients who received vorasidenib versus the placebo. And also, when we look at the median time to next intervention, which was that additional endpoint, it wasn't reached at data cutoff for the vorasidenib treated patients, but it was 17.8 months in the patients who received placebo, and the hazard ratio there was 0.26.

Now, as it relates to adverse events, when you look at the adverse events in the patients who received vorasidenib, the rate of grade 3 and 4 adverse events were low across the board. The most common adverse events that occurred in at least 15% of patients or more included fatigue and headache. They conducted the study during the COVID-19 pandemic, so COVID-19 infections were also prevalent. We saw some musculoskeletal pain, diarrhea, nausea, and seizures. Laboratory abnormalities, we did see some AST and ALT elevation, so it's going to be important for us to keep in mind what their transaminases look like. And we did see some neutropenias in some of the patients who were treated with therapy as well.

Overall, as a key takeaway, I think this therapeutic is a novel therapy in this patient population that has yet to have a very good treatment option in these astrocytomas or oligodendrogliomas. Thank you.