Servier promised in March that interim data from a phase 3 study would “shift the treatment paradigm” for a type of brain cancer that has long been stagnant in clinical research. Now, we’ve got the goods. Vorasidenib resulted in an “unprecedented” median 27.7 months of progression free survival (PFS) in patients with residual or recurrent grade 2 glioma with a certain mutation.
Patients treated also had a significant improvement in time to next intervention, which was a key secondary endpoint of the study. Servier trumpeted the results from the phase 3 INDIGO trial Sunday at the American Society of Clinical Oncology conference in Chicago. The company had previously teased in March that vorasidenib had beaten placebo on the primary endpoint at an interim analysis, but the specifics were kept under wraps.
INDIGO is a registration-enabling late-stage trial featuring patients with residual or recurrent grade 2 glioma, who have an isocitrate dehydrogenase 1/2 (IDH1/2) mutation and have undergone surgery as their only treatment. Gliomas are a common tumor that grow within the brain or spinal cord in the glial or precursor cells of the central nervous system. Patients with this type of cancer have a particularly poor prognosis, and available treatment options have high toxicities. There’s been little progress in finding more advanced treatments over the past few decades.
There are several different types of glioma. The 331-patient study had 172 people with oligodendroglioma and 159 with astrocytoma.
Vorasidenib met the primary endpoint of PFS and the key secondary endpoint of time to next intervention at the prespecified second interim analysis. On the PFS measure, the therapy hit 27.7 months compared to 11.1 on placebo. On the secondary measure, Servier said that the median time to next intervention was not reached for vorasidenib but was 17.8 months for placebo.
Servier said the PFS result was statistically significant and clinically meaningful, which a p-value of 0.000000067. The data cutoff was Sept. 6, 2022.
The INDIGO results demonstrate the impact of targeting these glioma mutations early, according to Servier’s Susan Pandya, M.D., vice president of clinical development and head of cancer metabolism global development for oncology and immuno-oncology.
Servier said the safety profile was “well tolerated” and consistent with previous phase 1 testing. The most common grade 3 adverse events were liver enzyme elevations, which can indicate liver damage and seizures. The rate of seizures was 4.2% for vorasidenib and 2.5% for placebo.
The FDA granted a fast-track designation to vorasidenib in March. The company will now work to establish a timeline for submission of an application for approval to the agency.
Servier picked up the therapy in the $1.8 billion acquisition of Agios Pharmaceuticals’ cancer unit in 2020. Vorasidenib was the jewel of the buyout, which also included two approved drugs, Idhifa and Tibsovo.