Newly approved brain cancer drug has ties to Duke University

The newly FDA-approved brain cancer therapy Voranigo (vorasidenib) has its roots in North Carolina. It is the product of research by Duke University's Darell Bigner and Bert Vogelstein of Johns Hopkins University and underwent clinical trials at Duke. 

Vorasidenib has been shown to slow the growth of a type of brain cancer known as low-grade IDH-mutant glioma. Servier Pharmaceuticals, which sponsored the drug’s clinical trials and is bringing it to market, describes the medicine as the first breakthrough for this type of cancer in almost 25 years. 

Diffuse gliomas with IDH mutations are the most common malignant primary brain tumors in adults under 50, with around 2,500 new cases diagnosed each year. These patients have limited treatment options and can experience impaired thinking, blurred vision, weakness and early death. 

Bigner was part of a collaboration with Vogelstein that led to the discovery of the IDH mutation. Patents arising from that early collaboration were licensed to industry through the Duke University Office for Translation & Commercialization, making vorasidenib the seventh drug currently on the market with ties to Duke intellectual property.

IDH mutation and tumor classification

“The discovery of the mutant IDH gene is one of the most important discoveries in neuro-oncology,” said Bigner. “The IDH mutation has been incorporated by the World Health Organization into the rapid and accurate diagnosis and classification of astrocytic, oligodendroglial and glioblastoma multiforme brain tumors. Never before has a single gene mutation contributed so greatly to classification.”

In 2023, Duke recruited Hai Yan after he completed a 5-year post-doctoral research fellowship with Vogelstein at Johns Hopkins. Additional research by the Duke and Johns Hopkins teams produced numerous publications on the pathological roles of IDH mutations, making it possible to develop targeted therapies that culminated in the approval of vorasidenib. 

“The development and approval of vorasidenib represent a significant milestone in the field of oncology, particularly in the treatment of brain cancers,” said Yan. “It validates the approach of targeting specific genetic mutations with precision therapies and reinforces the importance of personalized medicine in oncology.”

Clinical testing at Duke

More recently, Duke’s Katherine Peters was a lead investigator in the clinical trials for vorasidenib. The phase 3 trial, which involved more than 300 participants who had undergone no previous treatment other than surgery, showed that the drug more than doubled the time that elapsed before the cancer began to grow. 

The treatment also significantly increased the time before the tumor needed additional treatments, such as surgery or chemotherapy. The drug, which is taken orally once a day, was well tolerated, with less than 10% of patients experiencing serious side effects.

“It is exciting to have a drug specifically targeted for these patients by inhibiting the mutant IDH enzyme,” said Peters. “With vorasidenib being orally available, well-tolerated, and not [impairing] quality of life or cognition, we can extend people’s lives and delay the use of treatments such as radiation therapy and chemotherapy.” 

Studies are being done at Duke to see if vorasidenib could also help patients with high-grade IDH-mutant gliomas. Most of these studies are testing vorasidenib combined with immunotherapy.