Servier’s $1.8 Billion Acquisition Pays Off: FDA Approves First-In-Class Treatment for Two Types of Rare Brain Cancer

The Food and Drug Administration (FDA) has approved Servier Pharmaceuticals’ Voranigo for treating two types of low-grade gliomas. This anticipated blockbuster drug originates from Servier’s c acquisition of Agios Pharmaceuticals’ oncology division. Vorasidenib (Voranigo, formerly AG-881) is a first-in-class treatment for patients with IDH-mutant gliomas, marking Servier’s sixth approval for cancers with IDH mutations. 

Servier’s First-in-Class Voranigo for Patients with IDH-Mutant Gliomas

Servier Pharmaceuticals’ new drug, Vorasidenib, has received FDA approval for treating two rare types of brain cancer. Announced on Tuesday, this approval covers adults and adolescents aged 12 and older with Grade 2 astrocytoma or oligodendroglioma. Notably, Vorasidenib is a once-daily oral pill that targets mutant IDH1 and IDH2 enzymes, suitable for use after surgery. This marks the FDA’s first approval of a systemic therapy for these rare brain cancers driven by IDH1 or IDH2 mutations. Servier, based in France with its U.S. headquarters in Boston, will market the drug under the brand name Voranigo.

Astrocytoma and oligodendroglioma are gliomas that originate from central nervous system cells. Consequently, these low-grade gliomas commonly affect individuals in their 30s and 40s. Although rare, diffuse gliomas with IDH mutations are the most frequently diagnosed malignant primary brain tumors in those under 50. Surgery often serves as the initial treatment. If these cancers progress to high-grade gliomas, treatment options become limited to radiation and chemotherapy, which have various side effects. Therefore, Vorasidenib offers a new therapeutic option for these challenging conditions.

IDH stands for isocitrate dehydrogenase, an enzyme involved in the citric acid cycle that provides cellular energy. Moreover, mutations in IDH1 and IDH2 genes link to abnormal metabolism and various cancers, including gliomas.

Vorasidenib Significantly Extends Progression-Free Survival in IDH-Mutant Gliomas

Based on the Phase 3 INDIGO trial (NCT04164901) results, vorasidenib significantly improved progression-free survival (PFS) and delayed the time to the next intervention (TTNI). The placebo-controlled Phase 3 clinical trial involved 331 post-surgery patients with Grade 2 astrocytoma or oligodendroglioma who had IDH1 or IDH2 mutations. The trial excluded patients who had received prior treatments such as chemotherapy or radiation. Importantly, patients in the placebo group could switch to the treatment group if disease progression was confirmed by brain imaging.

In the trial, no deaths occurred in either group. However, progressive disease appeared in 28% of patients receiving the study drug, compared to 54% in the placebo group. Furthermore, the efficacy analysis showed that the time to the next therapeutic intervention was not reached for the study drug group, while it was 17.8 months for the placebo group.

In an interview with Targeted Oncology, Duke Cancer Center neuro-oncologist Dr. Katherine Peters explained the significance of the trial’s outcome. “What’s exciting is this development, which we haven’t seen in over 20 years. We found that patients receiving vorasidenib had a much-improved prognosis. Their progression-free survival extended to 27.7 months compared to 11 months in the placebo group. This represents a very large, statistically significant difference,” she said.

The recommended dose of Voranigo for adults is a 40 mg tablet taken once daily until disease progression or unacceptable toxicity occurs. For adolescents, the dosage depends on patient weight. Common adverse reactions include fatigue, headache, muscle pain, and diarrhea. Additionally, liver toxicity poses a risk; thus, the label advises clinicians to monitor liver function regularly.

Servier Acquires Agios Oncology Portfolio for $1.8 Billion; Agios to Receive Milestone Payment and Royalties for Voranigo

Voranigo, originally developed by Agios Pharmaceuticals, follows their earlier successes with the IDH2 inhibitor Idhifa and the IDH1 inhibitor Tibsovo, both for advanced acute myeloid leukemia. In a strategic shift towards rare diseases, Agios Pharmaceuticals, Inc., known for its expertise in cellular metabolism for genetically defined diseases, sold its oncology portfolio to French drugmaker Servier Pharmaceuticals, LLC, in early 2021 for $1.8 billion. Under the deal, Agios will receive a $200 million milestone payment for Voranigo’s approval and a 15% royalty from its sales. The acquisition aligns with Servier’s strategic goal to become a leading and innovative force in oncology, focusing on the malignant hematology market and the solid tumor arena.

Author

Bernice Lottering