In August, the FDA approved Servier’s Voranigo (vorasidenib) for treating low-grade brain cancer with IDH1 or IDH2 mutation. The approval marked a milestone for a French pharma that aims to be a leader in treatments for IDH mutant cancers.
Voranigo is the world’s first IDH1/IDH2 dual inhibitor to treat glioma with one of the mutations. Such an approach is believed to be more effective than single inhibitors in tackling the resistance issue. The pivotal study INDIGO showed that median progression-free survival (PFS) was 27.7 months for vorasidenib in contrast to a placebo’s 11.1 months. The time to next intervention (TTNI) was not reached with vorasidenib. The placebo took 17.8 months. The study also saw vorasidenib reduce tumor volume by 2.5% on average every six months. By contrast, tumor volumes grew 13.9% on the placebo.
Voranigo was approved under the FDA’s Project Orbis, an initiative that aims to expedite the approval process for novel candidates that meet efficacy and safety requirements, as well as largely improve quality of life. Before Voranigo, the standard treatment for glioma involves surgery, radiotherapy, and chemotherapy. With Voranigo, radiotherapy and chemotherapy could be significantly delayed, as it is “the first systemic therapy” approved for use after surgery to control the rare cancer, according to the FDA.
Servier wasted no time in bringing the drug to China. In late August, it started a Voranigo bridging study in Beijing, recruiting Asian glioma patients with IDH1/2 mutation.
“We are also actively talking to Chinese authorities in some specific areas to allow local Voranigo access before getting an official China NDA approval to meet some urgent demand,” said Servier China General Manager Manuel Ruiz at a recent media conference in Beijing. By “specific areas”, he was referring to the Boao Lecheng International Medical Tourism Pilot Zone in Hainan, the Tianzhu Comprehensive Bonded Zone in Beijing, and the Guangdong-Hong Kong-Macao Bay area. The three areas have a similar policy that allows locally selected hospitals to prescribe certain foreign novel drugs approved outside China.
Servier’s Chinese partner AmoyDx, a diagnostic device supplier based in Xiamen, Fujian Province, will develop a Voranigo companion diagnostic to help commercialize the drug.
Compared with the fierce competition among PD1/PDL1 antibodies, IDH inhibitors are a greenfield, and Servier no doubt is leading the race. Aside from Voranigo, it also owns the IDH1 inhibitor Tibsovo (ivosidenib) and IDH2 inhibitor Idhifa (enasidenib). China has not yet approved any IDH inhibitors, but it has two IDH assets in Phase III studies: IDH1/IDH2 inhibitor HMPL306 from Hutchmed, and TQB3454, an IDH1 inhibitor from Chiatai Tianqing.
Outside China, only US biotech firm Rigel has an FDA-approved IDH1 inhibitor, the AML treatment Rezlidhia (olutasidenib).
To keep its leading position, Servier is investing in studies to explore more indications. For example, in the US it has started a Phase II study for vorasidenib in combination with Keytruda (pembrolizumab) to treat higher-grade astrocytoma as a first-line treatment. It is also conducting Phase Ib/II studies that combine vorasidenib with temozolomide to treat IDH mutant glioma. Both Phase Ib and Phase II studies excluded grade 1 gliomas.
Aside from Voranigo, Servier is also actively doing early-stage studies for Tibsovo to explore indications including IDH1 mutant AML, cholangiocarcinoma, chondrosarcomas, and myelodysplastic syndrome.
Servier made oncology one of its core research areas in 2018 when it bought Shire’s oncology business. In 2020 it bought the Danish antibody developer Symphogen. Its latest purchase happened in May this year when it bought the US biotech firm Agios. The deal gave Servier full access to its core asset vorasidenib.
Servier is seeking partners for novel cancer drug discovery, such as working with the American biotech firm GNS on multiple myeloma drug discovery and the French biotech Oncodesign Precision on pancreatic cancer therapies. It also signed a research agreement with the French hospital Gustave Roussy Institute for R&D programs.
Today, Servier’s oncology pipeline includes more than a dozen assets, with targets including MET, TIM3, CD73, and MAT2A.
Like fellow MNCs, Servier is no stranger to AI. It teamed up with AI companies like Aquemia and Owkin to develop innovative chemical drugs and developed an in-house AI platform named Patrimony for drug discovery.
Servier’s investment in oncology has rewarded the company generously too. According to its 2022 annual report, it saw oncology drug-generated revenue grow 26.7% year-on-year to over EUR 1 billion (USD 1.1 billion). Revenues from its oncology business now account for 20% of Servier’s total revenue, compared with 17.4% in 2021. With the approval of Voranigo, Servier expects the oncology business will bring in more than EUR 3 billion in 2030.