Recently, Servier spent $780 million to acquire BDTX-4933, a small molecule drug in Phase 1 clinical trials targeting RAS mutations and RAF changes in solid tumors, from Black Diamond Therapeutics. Today, Servier's competitive position is threatened by challenges in the chronic disease drug market, and it is actively looking for a new way forward, with the latest goal of entering the field of oncology. In recent years, Servier has continuously strengthened its oncology pipeline through acquisitions and introductions, and has become a "dark horse" in the field of oncology treatment that cannot be underestimated.

IDH inhibitor frontrunner

Isocitrate dehydrogenase (IDH) is a key rate-limiting enzyme in the tricarboxylic acid cycle. There are three isoenzymes of IDHs, namely IDH1, IDH2 and IDH3. The functional loss caused by mutations in IDH1 and IDH2 will directly affect the product composition - α-ketoglutarate is converted into the carcinogenic metabolite 2-hydroxyglutarate, promoting the occurrence of cancer. IDH1 mutations are more common in solid tumors, IDH2 mutations are common in hematological tumors, but IDH3 mutations are not common.

In today's era of target involution, the field of IDH inhibitors is like a blue ocean. In this blue ocean track, Servier is far ahead, not only with the IDH1/2 inhibitor Voranigo (vorasidenib), but also the IDH1 inhibitor Tibsovo (ivosidenib) and IDH2 inhibitor Idhifa (enasidenib) that have been launched. All three products were acquired by Servier in 2020 when it acquired the oncology business of Agios Pharmaceuticals for US$1.8 billion.

In August 2024, Servier's oncology business around IDH reached a milestone: the FDA approved Voranigo (vorasidenib) for the treatment of low-grade diffuse brain gliomas carrying IDH mutations. This dual inhibitor, which can penetrate the blood-brain barrier and simultaneously targets IDH1 and IDH2 mutations, is the first FDA-approved systemic therapy for this type of patient. Looking at the specific data, the median progression-free survival (PFS), the primary endpoint of vorasidenib, reached 27.7 months, while that of the placebo group was 11.1 months. The key secondary endpoint of time to next intervention (TTNI) was statistically significant, with the median TTNI in the vorasidenib group not yet reached, compared with 17.8 months in the placebo group, a statistically significant difference. Other data showed that the average tumor volume in the vorasidenib group decreased by 2.5% every 6 months, while the average tumor volume in the placebo group increased by 13.9% every 6 months.

At the same time, Servier is further exploring the potential of vorasidenib. It has launched a Phase 2 clinical trial for first-line treatment of grade 4 astrocytoma, a Phase 1 clinical trial in combination with the PD-1 inhibitor pembrolizumab, and a Phase 1b/2 clinical study in combination with temozolomide for the treatment of IDH1 or IDH2 mutant gliomas. The clinical layout of vorasidenib shows Servier's plans for product expansion toward first-line treatment and combination therapy.

Servier's IDH1 inhibitor ivosidenib has been on the market for many years and has obtained four indications, covering both blood tumors and solid tumors with IDH1 mutations. As for the expansion of ivosidenib's indications, Servier has clinical studies underway in the first-line and second-line treatment of IDH1-mutated cholangiocarcinoma, first-line and second-line chondrosarcoma, first-line acute myeloid leukemia (AML), and first-line treatment of myelodysplastic syndrome (MDS).

In contrast, other products in the IDH track, in addition to the already launched Rezlidhia (olutasidenib), Hutchison Medicine's IDH1/2 inhibitor HMPL-306 has made the fastest progress and is in the Phase 3 clinical stage. Other similar research drugs that have entered the clinical stage include Betta Pharmaceuticals' BPI-221351, Eli Lilly's LY3410738, and Nerviano Medical Sciences' NMS-173. It can be seen that in the future, Servier will lead the IDH track for a long time, whether it is dual-target or dual-target. In addition, as the indications of vorasidenib and ivosidenib continue to advance to the front line, it is still difficult for related products to keep up with Servier's pace.

Ambitious

Servier's foray into the oncology field began with the acquisition of Shire's oncology business in 2018, including Oncospar (pegaspargase) (a drug used to treat acute lymphoblastic leukemia) and Onivyde (irinotecan liposome injection). In March 2022, Onivyde was approved in China, breaking the situation in which no treatment options for pancreatic cancer were approved in China for nearly 20 years after gemcitabine was approved for pancreatic cancer indications in 1999. It brought innovative solutions to pancreatic cancer patients and was also Servier's first oncology product launched in China.

Then, it became a top player in IDH inhibitors by acquiring Agios Pharmaceuticals, and strengthened its tumor antibody research and development capabilities by acquiring Denmark's Symphogen. In addition, Servier continues to expand its early clinical pipeline through external cooperation models, including cooperating with GNS to develop multiple myeloma drugs, cooperating with Oncodesign to explore new targets for pancreatic cancer treatment, and signing an oncology cooperation framework agreement with Gustave Roussy.

Gastrointestinal tumors have always been a key area of focus for Servier. Lonsurf (trifluridine + tipiracil), which was introduced from TAIHO at a cost of US$130 million in 2015, has become the third-line standard treatment for colorectal cancer. In addition, Servier has also worked hard on the combination therapy of Lonsurf: compared with the combination regimen with bevacizumab, the single drug can significantly improve the PFS and OS of adult patients with mCRC, and the indication has been approved by the FDA. The combination regimen with the EGFR monoclonal antibody S95026 (futuximab/modotuximab) has been clinically confirmed in terms of efficacy and safety.

Currently, other oncology products under development in Servier's pipeline cover multiple targets such as MET, TIM3, CD73, NKG2A, MAT2A, etc. The drug types include both small molecules and antibody drugs, and the indications are expanded to solid tumors such as non-small cell lung cancer.

In addition, at a time when MNCs are embracing AI, Servier is no exception. It has collaborated with artificial intelligence companies Aqemia and Owkin to develop small molecule drugs for innovative targets. Earlier this year, it reached a five-year collaboration with Google Cloud, focusing on artificial intelligence and generative AI technologies to help improve the efficiency of new drug research and development. In addition, Servier has also established its own high-throughput AI platform Patrimony, and has achieved a number of major results using the platform.

Currently, the field of oncology has become a new pillar of Servier's strategic growth. The financial report shows that Servier's consolidated revenue in fiscal 2024 reached 5.902 billion euros, a year-on-year increase of 10.8%; of which sales revenue in the field of oncology was 1.430 billion euros, accounting for 24.2% of the group's consolidated revenue, an increase from 20.2% in fiscal 2023.

Servier released its 2030 group development goals in 2022, expecting to achieve 1 billion euros in oncology revenue in 2025 and at least 3 billion euros in 2030. Combined with the sales performance of oncology products that have been launched, Servier has formed a complete layout of early innovative discovery, clinical expansion and continuous commercialization in the field of oncology. It is believed that with the approval of vorasidenib and the oncology business around IDH, and the continuous development of innovative oncology products with the help of AI technology, Servier's continuous planning in the field of oncology will help it achieve its goals.

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