Fierce competition for FGFR inhibitors: 3 approved, many in research

The field of domestic FGFR inhibitors ushered in a number of developments

On July 9, Innovent announced that NMPA has accepted the marketing application of its FGFR 1/2/3 inhibitor pemigatinib tablets.

On the same day, according to the official website of CDE, the clinical trial application of Hutchison Medicine’s FGFR 1/2/3 inhibitor HMPL-453 tartrate tablets was also accepted

1.

FGFR, the fibroblast growth factor receptor, is one of the subfamily of receptor tyrosine kinases, including four subtypes of FGFR1, FGFR2, FGFR3, and FGFR4.

FGFR is currently one of the hot targets focused on "unlimited cancer types" therapy.

Erdafitinib is an oral FGFR kinase inhibitor discovered by Astex.

Pemigatinib is a potent and selective oral inhibitor for FGFR subtypes 1, 2, and 3 discovered and developed by Incyte.

Infigratinib is an innovative, oral, selective and potent inhibitor of FGFR subtypes 1, 2, and 3.

2.

The development of FGFR inhibitors has brought the hope of targeted therapy for FGFRs-driven tumor patients.

SY-4798 is a new generation of selective FGFR4 small molecule inhibitor with complete intellectual property rights and a new compound structure independently developed by First Pharmaceutical Holdings

3D185 is a small molecule inhibitor targeted by FGFR 1/2/3.
Preclinical studies have shown that 3D185 has strong anti-tumor activity, excellent PD-PK characteristics, low toxicity and high bioavailability, and has CSF1-R targeting Function, suitable for combined treatment with PD-1/PD-L1 in the field of tumor immunotherapy
.
In August 2018, Siddi Medical and Haihe Biopharma reached a strategic cooperation on the drug, and obtained the license to develop, produce and commercialize the drug on a global scale for the treatment of tumors and pulmonary fibrosis
.

HMPL-453 is a potential best-in-class high-selectivity and high-efficiency small molecule inhibitor.
Its inhibitory effect on FGFR1/2/3 is IC50 at a low nanomolar level.
After 292 kinases were screened, it showed good selectivity
.
HMPL-453 exhibits potent anti-tumor activity in tumor models with abnormal FGFR activation
.

Fisogatinib is an oral, potent and highly selective FGFR4 inhibitor.
It is currently in Phase II clinical trials and is indicated for hepatocellular carcinoma
.
The drug was developed by Blueprint Medicines.
In 2018, CStone Pharmaceuticals obtained the rights to the drug and Avapritinib and BLU-667 in Greater China
.

Gunagratinib, the second-generation pan-FGFR inhibitor independently developed by Nuocheng Jianhua, has a strong inhibitory effect on the four kinases of the FGFR family, especially in the treatment of intrahepatic cholangiocarcinoma and other solid tumors.
This June Was awarded the FDA orphan drug designation for the treatment of cholangiocarcinoma
.

BPI-17509 is a potent and highly selective FGFR1/2/3 small molecule oral inhibitor with a brand-new chemical structure.
It is intended to be used for the treatment of solid tumors and other types of tumors with FGFR gene mutations.
It is currently in clinical trials for solid tumors.
It is progressing smoothly
.
BPI-43487 is a potent and highly selective covalent non-reversible inhibitor of FGFR4.
It is intended to be used for the treatment of FGF19-amplified hepatocellular carcinoma, cholangiocarcinoma and other solid tumors.
The drug has been approved in China.
Clinical
.

ABSK091 (AZD4547) is a small molecule FGFR subtype 1, 2 and 3 highly effective and selective inhibitor developed by AstraZeneca.
In November 2019, Heyu Medicine obtained the global development, production and commercialization of the drug from AstraZeneca.
Equity
.
In December 2020, the Phase 1b/2 clinical trial application for the treatment of urothelial cancer patients with FGFR2 or FGFR3 mutations was approved by the NMPA
.
ABSK011 is an innovative small-molecule oral inhibitor of FGFR4 independently developed by Heyu Medicine and has global intellectual property rights.
Currently, it has initiated phase 1b clinical trials for the treatment of advanced hepatocellular carcinoma overexpressing FGF19 in the Mainland
.

Derazantinib is a potent, oral FGFR kinase family small molecule inhibitor developed by ArQule.
It has strong activity on FGFR1, 2, 3, and the drug can also inhibit CSF1R (colony stimulating factor 1 receptor kinase, its The mediated signal is very important for the maintenance of tumor-promoting macrophages and has been identified as a potential target of anti-cancer drugs)
.
In February 2018, Roivant Sciences and ArQule reached a partnership to obtain the authorization to develop and commercialize the drug in Greater China
.
In April 2018, Basilea Pharmaceutica signed a license agreement with ArQule
.
At present, the drug has been granted orphan drug designation for the treatment of intrahepatic cholangiocarcinoma in the United States and the European Union, and its FIDES-01 study cohort 1 for the treatment of cholangiocarcinoma has achieved top-line results
.

TA-46 is a soluble recombinant human FGFR3 bait protein.
By binding to FGF, it prevents FGF from binding to mutant FGFR3, thereby inhibiting the over-activated FGFR3 signaling pathway and normalizing the pathway
.
Currently, TA-46 has completed phase I clinical trials and is being developed as a weekly subcutaneous injection for the treatment of achondroplasia in children and adolescents
.
In the United States and the European Union, the drug has been granted orphan drug designation
.
The drug was developed by Therachon, and Pfizer acquired the drug through the acquisition of Therachon in 2019
.

Futibatinib (TAS-120) is an oral, selective, and irreversible small molecule inhibitor of FGFR1-4.
It irreversibly covalently binds to the ATP binding "pocket" of FGFR1-4 to inhibit FGFR-mediated signal transduction, thereby reducing Proliferation of tumor cells carrying FGFR1-4 gene mutations
.
In April 2021, the drug was granted a breakthrough drug qualification by the FDA for the treatment of patients with locally advanced or metastatic cholangiocarcinoma carrying FGFR2 gene rearrangement or fusion
.
Analysis of the interim data of its 2 study FOENIX-CCA2 for the treatment of cholangiocarcinoma showed that in 67 patients with intrahepatic cholangiocarcinoma with FGFR2 gene fusion or rearrangement with a follow-up time of more than 6 months, futibatinib reached an objective response rate of 37.
3%.
The disease control rate was 82.
1%, the median duration of remission reached 8.
3 months, and the median progression-free survival reached 7.
2 months
.

E7090 is a small molecule FGFR1/2/3 inhibitor developed by Eisai.
It is currently undergoing phase 2 clinical trials in Japan and China
.
In February of this year, the drug was granted orphan drug designation by the FDA for the treatment of unresectable biliary tract cancer with the FGFR2 fusion gene
.

FGFR is currently a popular target for targeted drug research and development, and the competition is relatively fierce.
At present, many domestic and foreign companies are deployed.
It is believed that with the continuous efforts of enterprises, more FGFR targeted drugs will be approved in the future
.