Pemigatinib, sold under the brand name Pemazyre, is an anti-cancer medication used for the treatment of bile duct cancer. Pemigatinib works by blocking FGFR2 in tumor cells to prevent them from growing and spreading. Pemigatinib belongs to a group of small molecule FGFR tyrosine kinase inhibitors and is an orally administered targeted therapy designed to inhibit aberrant FGFR signaling associated with FGFR2 fusions and rearrangements. At the molecular level it binds the ATP pocket of FGFR kinases to inhibit autophosphorylation and downstream signaling pathways such as RAS MAPK, PI3K AKT and STAT, which leads to reduced proliferation and induction of apoptosis in FGFR-driven tumor cells. Clinically it is used in patients whose tumors harbor FGFR2 genetic alterations after prior systemic therapy, and typical development and quality control describe it as an orally bioavailable, selective FGFR inhibitor with drug product formulation and stability requirements consistent with regulatory guidance.
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Parent: Pemigatinib
![3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-((ethylamino)methyl)-3,4-dihydro-1H-pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidin-2(7H)-one](https://veeprho.com/wp-content/uploads/2023/04/3-2-6-difluoro-3-5-dimethoxyphenyl-1-ethyl-8-ethylamino-methyl-3-4-dihydro-1H-pyrrolo-3-2-5-6-pyrido-4-3-d-pyrimidin-2-7H-one.png "3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-((ethylamino)methyl)-3,4-dihydro-1H-pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidin-2(7H)-one")
Parent: Pemigatinib
Typical analytical and specification considerations for pemigatinib active pharmaceutical ingredient include a stated assay purity target equal to or greater than 98.0 percent by validated HPLC, a total related substances limit not to exceed 1.0 percent w by w under routine release testing, and individual identified related compounds limited to 0.2 percent w by w or lower. Unidentified or unspecified impurities are commonly controlled at a reporting threshold of 0.1 percent w by w with a qualification threshold appropriate to the impurity risk assessment. Potential process and degradation impurities include desmethyl and N oxide species, dehalogenated analogs and positional isomers; known genotoxic impurities are controlled to limits consistent with ICH M7, typically at or below 0.05 percent w by w depending on acceptable intake calculations. Stability indicating assays are established by forced degradation studies and use orthogonal techniques such as LC MS for identification and quantitation, and control of residual solvents and elemental impurities follows ICH Q3C and Q3D guidance.
Pemigatinib is used to treat cholangiocarcinoma, also called bile duct cancer, in patients whose tumors harbor FGFR2 fusions or rearrangements and who have received prior systemic therapy. Its use is guided by molecular testing that identifies actionable FGFR2 alterations.
In the pivotal clinical program for patients with FGFR2 fusions or rearrangements, objective response rates observed were in the low to mid 30 percent range among evaluable patients, with a subset achieving durable responses. Effectiveness is strongly dependent on the presence of FGFR2 alterations and prior treatment history.
Pemigatinib is a selective small molecule inhibitor of FGFR kinases that binds the ATP binding site, preventing receptor autophosphorylation and blocking downstream signaling cascades including RAS MAPK, PI3K AKT and STAT. This inhibition reduces tumor cell proliferation, survival and metastatic potential in FGFR driven cancers.
