Pemigatinib

Pemigatinib (INN),[2] sold under the brand name Pemazyre, is a medication for the treatment of adults with previously treated, unresectable locally advanced or metastatic bile duct cancer (cholangiocarcinoma) with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test.[3][4] Pemigatinib works by blocking FGFR2 in tumor cells to prevent them from growing and spreading.[3]

Pemigatinib
Clinical data
Trade namesPemazyre
Other namesINCB054828
AHFS/Drugs.comMonograph
MedlinePlusa620028
License data
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC24H27F2N5O4
Molar mass487.508 g·mol−1
3D model (JSmol)

Pemigatinib belongs to a group of medicines called protein kinase inhibitors.[5] It works by blocking enzymes known as protein kinases, particularly those that are part of receptors (targets) called fibroblast growth factor receptors (FGFRs).[5] FGFRs are found on the surface of cancer cells and are involved in the growth and spread of the cancer cells.[5] By blocking the tyrosine kinases in FGFRs, pemigatinib is expected to reduce the growth and spread of the cancer.[5]

The most common adverse reactions are hyperphosphatemia and hypophosphatemia (electrolyte disorders), alopecia (spot baldness), diarrhea, nail toxicity, fatigue, dysgeusia (taste distortion), nausea, constipation, stomatitis (sore or inflammation inside the mouth), dry eye, dry mouth, decreased appetite, vomiting, joint pain, abdominal pain, back pain and dry skin.[3][4] Ocular (eye) toxicity is also a risk of pemigatinib.[3][4]

Medical uses

Cholangiocarcinoma is a rare form of cancer that forms in bile ducts, which are slender tubes that carry the digestive fluid bile from the liver to gallbladder and small intestine.[3] Pemigatinib is indicated for the treatment of adults with bile duct cancer (cholangiocarcinoma) that is locally advanced (when cancer has grown outside the organ it started in, but has not yet spread to distant parts of the body) or metastatic (when cancer cells spread to other parts of the body) and who have tumors that have a fusion or other rearrangement of a gene called fibroblast growth factor receptor 2 (FGFR2).[3] It should be used in patients who have been previously treated with chemotherapy and whose cancer has a certain type of abnormality in the FGFR2 gene.[6]

History

Pemigatinib was approved for use in the United States in April 2020 along with the FoundationOne CDX (Foundation Medicine, Inc.) as a companion diagnostic for patient selection.[3][4][7]

The approval of pemigatinib in the United States was based on the results the FIGHT-202 (NCT02924376) multicenter open-label single-arm trial that enrolled 107 participants with locally advanced or metastatic cholangiocarcinoma with an FGFR2 fusion or rearrangement who had received prior treatment.[3][4][6] The trial was conducted at 67 sites in the United States, Europe, and Asia.[6] During the clinical trial, participants received pemigatinib once a day for 14 consecutive days, followed by 7 days off, in 21-day cycles until the disease progressed or the patient experienced an unreasonable level of side effects.[3][4][6] To assess how well pemigatinib was working during the trial, participants were scanned every eight weeks.[3] The trial used established criteria to measure how many participants experienced a complete or partial shrinkage of their tumors during treatment (overall response rate).[3] The overall response rate was 36% (95% CI: 27%, 45%), with 2.8% of participants having a complete response and 33% having a partial response.[3] Among the 38 participants who had a response, 24 participants (63%) had a response lasting six months or longer and seven participants (18%) had a response lasting 12 months or longer.[3][4]

The U.S. Food and Drug Administration (FDA) granted the application for pemigatinib priority review, breakthrough therapy and orphan drug designations.[3][4][8][9] The FDA granted approval of Pemazyre to Incyte Corporation.[3]

On 24 August 2018, orphan designation (EU/3/18/2066) was granted by the European Commission to Incyte Biosciences Distribution B.V., the Netherlands, for pemigatinib for the treatment of biliary tract cancer.[5] On 17 October 2019, orphan designation EU/3/19/2216 was granted by the European Commission to Incyte Biosciences Distribution B.V., the Netherlands, for pemigatinib for the treatment of myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1, or with PCM1-JAK2.[10] On 28 January 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a conditional marketing authorization for the medicinal product Pemazyre, intended for the second-line treatment of advanced or metastatic cholangiocarcinoma characterized by fusion or rearrangements of fibroblast growth factor receptor 2.[11] The applicant for this medicinal product is Incyte Biosciences Distribution B.V.[11]

References
  1. "Pemazyre- pemigatinib tablet". DailyMed. Retrieved 1 February 2021.
  2. World Health Organization (2018). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 80". WHO Drug Information. 32 (3): 479. hdl:10665/330907.
  3. "FDA Approves First Targeted Treatment for Patients with Cholangiocarcinoma, a Cancer of Bile Ducts". U.S. Food and Drug Administration (FDA) (Press release). 17 April 2020. Retrieved 17 April 2020. This article incorporates text from this source, which is in the public domain.
  4. "FDA grants accelerated approval to pemigatinib for cholangiocarcinoma". U.S. Food and Drug Administration (FDA). 17 April 2020. Retrieved 20 April 2020. This article incorporates text from this source, which is in the public domain.
  5. "EU/3/18/2066". European Medicines Agency (EMA). 19 December 2018. Retrieved 20 April 2020. This article incorporates text from this source, which is in the public domain.
  6. "Drug Trials Snapshot: Pemazyre". U.S. Food and Drug Administration (FDA). 17 April 2020. Retrieved 5 May 2020. This article incorporates text from this source, which is in the public domain.
  7. "Pemazyre: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved 21 April 2020.
  8. "Pemigatinib Orphan Drug Designation and Approval". U.S. Food and Drug Administration (FDA). Retrieved 19 April 2020.
  9. "Pemigatinib Orphan Drug Designation and Approval". U.S. Food and Drug Administration (FDA). Retrieved 19 April 2020.
  10. "EU/3/19/2216". European Medicines Agency (EMA). 23 January 2020. Retrieved 19 April 2020. This article incorporates text from this source, which is in the public domain.
  11. "Pemazyre: Pending EC decision". European Medicines Agency (EMA). 29 January 2021. Retrieved 2 February 2021. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.

Further reading
  • "Pemigatinib". Drug Information Portal. U.S. National Library of Medicine.
  • "Pemigatinib". National Cancer Institute.
  • Clinical trial number NCT02924376 for "Efficacy and Safety of Pemigatinib in Subjects With Advanced/Metastatic or Surgically Unresectable Cholangiocarcinoma Who Failed Previous Therapy - (FIGHT-202)" at ClinicalTrials.gov
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