Pemigatinib

Evidence Level: L5

Predicted Indications: 9

Pemigatinib

Pharmacist Assessment Report

Pemigatinib: From an FGFR-Driven Cancer Indication to Multiple Endocrine Neoplasia

One-Sentence Summary

Pemigatinib is a selective FGFR1-3 kinase inhibitor marketed in Canada as PEMAZYRE. The TxGNN model predicts it may be effective for multiple endocrine neoplasia, but there are currently 0 clinical trials and 0 publications supporting this prediction. It rests on a computational prediction alone.

Quick Overview

Item	Content
Original Indication	Not available in the data compiled for this report (Canadian license indication text is blank)
Predicted New Indication	Multiple endocrine neoplasia
TxGNN Prediction Score	0.9971
Evidence Level	L5
Canada Market Status	Marketed (marketed DINs: 3 of 3)
Number of DINs	3 (marketed: 3)
Recommended Decision	Hold

Why is This Prediction Reasonable?

Pemigatinib is a selective inhibitor of FGFR1-3. Detailed mechanism of action data is not available in the data compiled for this report, so this description is based on the drug’s known class.

Multiple endocrine neoplasia (MEN) syndromes are driven mainly by loss of MEN1 (menin) and by RET activation, not by FGFR signaling. The only link is speculative: FGFR involvement in neuroendocrine tumour growth. The high TxGNN score (0.9971) is a computational output. No trials or literature back it up, so the mechanistic rationale should be treated as weak.

Other top-ranked predictions are even less plausible. Several look like TxGNN model (deep learning) artifacts: amenorrhea, two veterinary herpesvirus diseases (infectious bovine rhinotracheitis and malignant catarrhal fever), and cytomegalovirus infection. Several ALS entries are also predicted. FGF/FGFR signaling is generally neurotrophic, so inhibiting it could be harmful in ALS. The most biologically plausible alternative is HER2-positive breast carcinoma, where FGFR signaling has been linked to resistance to HER2-targeted therapy. That link is indirect, and the only retrieved paper is a general kinase inhibitor review (PMID 33513356, 2021, Pharmacological Research) with no pemigatinib-specific efficacy or safety data.

Clinical Trial Evidence

Currently no related clinical trials registered.

Literature Evidence

Currently no related literature available for the predicted indication of multiple endocrine neoplasia.

Canada Market Information

DIN	Product Name	Dosage Form	Approved Indication
02519941	PEMAZYRE	Not specified	Not specified
02519933	PEMAZYRE	Not specified	Not specified
02519968	PEMAZYRE	Not specified	Not specified

All three licenses are valid single-ingredient products.

Cytotoxicity

Item	Content
Cytotoxicity Classification	Targeted therapy (selective FGFR1-3 kinase inhibitor)
Myelosuppression Risk	Please refer to the package insert warnings and precautions
Emetogenicity Classification	Please refer to the package insert warnings and precautions
Monitoring Items	Please refer to the package insert warnings and precautions. Endocrine and phosphate-related effects are expected with FGFR inhibitors, so serum phosphate monitoring is reasonable.
Handling Protection	Please refer to the package insert warnings and precautions

Safety Considerations

Drug Interactions: The interaction screening returned 50 interacting drugs in total. Several are rated Major, including:

Aprepitant
Dexamethasone
Clarithromycin
Cobicistat
Lumacaftor
Chloramphenicol
Erythromycin
Ketoconazole
Fluconazole

Moderate-level interactions include cimetidine, clotrimazole, deferasirox, ivacaftor, zafirlukast, griseofulvin, elagolix and osilodrostat, among others. Many of these are CYP3A-modulating agents, so co-medication needs careful review.

For warnings and contraindications, please refer to the package insert for safety information.

Conclusion and Next Steps

Decision: Hold

Rationale: The prediction is supported only by a model score. There are no trials or publications, and the mechanistic link between FGFR inhibition and MEN syndromes is weak. The package insert safety data are also missing, which blocks safety screening.

To proceed, the following is needed:

Health Canada package insert warnings and contraindications (blocking gap)
Mechanism of action data from DrugBank
Targeted literature review of FGFR signaling in neuroendocrine and MEN-related tumours
Preclinical or mechanistic studies to justify any move beyond L5
Consider prioritising HER2-positive breast carcinoma, which has a more plausible, though still indirect, rationale
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.