FGFR, fibroblast growth factor receptor (FGFR), is one of the most popular targets for "unlimited cancer" therapy. It is an important member of the receptor family of tyrosine kinases, which consists of four highly conserved transmembrane receptor tyrosine kinases (FGFR1-4) and a receptor FGFR5 (also known as FGFRL1) that binds to FGF ligands but lacks an intracellular kinase domain.
Normal physiological conditions, FGFR and its ligand fibroblast growth factor (FGF), FGFR dimers was synthesized and its phosphorylation, activation of downstream signaling pathways, such as the JAK/STAT pathway, phospholipase C, these signal transduction pathways in multiple physiological processes such as cell proliferation, differentiation, migration and apoptosis in both plays a vital role.
However, FGFR is susceptible to various somatic aberrations, and common mutations such as overexpression, point mutation, and gene translocation occur, leading to carcinogenesis. Studies have found that FGFR gene variants are generally widespread in solid tumors such as lung cancer, liver cancer, intrahepatic cholangiocarcinoma, breast cancer, gastric cancer, uterine cancer and bladder cancer, and the types and frequencies of FGFR mutations are also different among different cancer types.
4 models have been approved, the potential market to attract continuous cooperation
FGFR inhibitors can inhibit tumor growth by blocking FGFR-mediated signaling pathway. In recent years, FGFR inhibitors have entered the harvest period, and one inhibitor has been approved every year since 2019. Up to now, 4 inhibitors have been approved globally, of which only Pemazyre has been approved in China.
The four FGFR inhibitors that have been approved are administered orally once daily, primarily for cholangiocarcinoma. None of the four FGFR inhibitors has entered the blockbuster category. However, Pemazyrehad sales of $25.9 million in 2020 and $68.5 million in 2021.
And the industry very bullish on FGFR inhibitors, NatureReviewDrugDiscovery Balversa2024 is expected annual sales is expected to reach $1.2 billion, EVP predict Truseltiq2026 annual sales of up to $253 million.
However, FGFR is the next "unlimited cancer" new target, related inhibitors are self-evidently expensive.
Balversa is priced between $10,080 and $22,680 per treatment course for 28 days. Pemazyre is listed at $17,000 per course of treatment, with an average treatment duration of about six months and eight or nine sessions, costing about $136,000 to $153,000 per patient. Truseltiq costs $21,500 a month, or about $129,000 every six months. The high cost of treatment makes ordinary patients "prohibitive", can only see from a distance.
However, as a potential stock, and the industry is optimistic about the market prospects; Major pharmaceutical companies have entered the market to cooperate in the development of FGFR inhibitors. For example, Balversa was discovered by Astex, and in 2008 Johnson & Johnson reached an exclusive global licensing and cooperation agreement with Astex for the drug.
Several FGFR inhibitors are in the pipeline
At present, there are several FGFR inhibitors in development worldwide that have entered clinical trials, including Bayer's Rogaratinib and Astrazeneca's ABSK091 (AZD4547), which have entered phase 3 clinical trials. As can be seen from the table below, the indications for FGFR inhibitors in development are increasingly diverse, starting to involve solid tumors such as non-small cell lung cancer and gastric cancer, as well as achondroplasia. Moreover, the targets of FGFR inhibitors are becoming more and more detailed. FGFR3 inhibitors, FGFR4 inhibitors and FGFR2b inhibitors have been developed by companies. In addition, FGFR inhibitors have become more diverse, with the emergence of monoclonal antibodies (e.g., bemarituzumab, Vofatamab) and radionuclide conjugated agents (e.g., FPI-1966).It is worth mentioning that Chinese pharmaceutical companies are also actively laying out the FGFR inhibitor market. In addition to independent research and development, Chinese pharmaceutical enterprises also actively introduce from outside, For example, in 2017, Reding Pharmaceutical introduced bemarituzumab from FivePrime, in 2018, Bashistone Pharmaceutical introduced fisogatinib from BlueprintMedicines, in 2018, Lunsen Pharmaceutical introduced derazantinib from ArQule, in 2018, Cinda Bio from I ncyte introduced pemigatinib, and in 2019, Reputation introduced AZD4547 from Astrazeneca.
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Publicly available data show that the overall annual incidence of FGFR-related solid tumors worldwide has grown from 4.4 million in 2016 to 4.9 million in 2020, at a compound annual growth rate of 3.0%, and is projected to grow to 6.8 million by 2035.With the increase of patient volume, the market size of FGFR inhibitors will continue to expand. The global pan-FGFR inhibitor market will reach $21.5 billion in 2035, according to the company's prospectus. However, highly selective FGFR inhibitors have not yet formed a market scale. Moreover, with the development of highly selective FGFR inhibitors, the market prospect of FGFR inhibitors is more promising.
