vimseltinib

Action and Spectrum

Actions and Spectrum:

This pharmaceutical medication functions as both a Colony-Stimulating Factor 1 Receptor (CSF1R) inhibitor and a switch-control kinase inhibitor. This drug concentrates on tenosynovial giant cell tumor (TGCT) because the disease expresses dysfunctional CSF1 which drives excessive CSF1 production.

The drug blocks tumor growth by suppressing the proliferation of CSF1R-expressing cells in vitro through its ability to prevent CSF1R autophosphorylation and subsequent CSF1 ligand-induced signaling.

Drug Interaction

Adverse Reaction

Adverse Reaction

>50%

All grades

• Peripheral edema (60%)
• AST increased (92%)
• Fatigue (59%)

>10-50%

All grades

Lacrimation increased (12%)

Neuropathy (12%)

Calcium decreased (13%)

Magnesium increased (13%)

ALP increased (14%)

Creatinine increased (17%)

Hypertension (17%)

ALT increased (24%)

Leukocytes decreased (29%)

Pruritus (29%)

Neutrophils decreased (31%)

Face edema (31%)

Peripheral edema (33%)

Cholesterol increased (43%)

Rash (47%)

1-10%

Other Serious ADRs (≥1%)

Cellulitis (1.2%)

Subcutaneous abscess (1.2%)

Grade 3 or 4

Neuropathy (1.2%)

Magnesium increased (1.2%)

Neutrophils decreased (1.2%)

Face edema (1.2%)

Peripheral edema (1.2%)

Fatigue (1.2%)

Pruritus (2.4%)

Peripheral edema (3.6%)

Rash (3.6%)

Hypertension (4.8%)

All Grades

Blurred vision (6%)

Dry eye (10%)

Black Box Warning

Black box warning:

None

Contraindication / Caution

Contraindications/caution:

The use of this medication should be approached cautiously because similar CSF1R inhibitors may cause hepatic damage therefore it should be avoided in patients with liver disease while keeping track of liver function test results.

Allergic Reactions are possible due to FD&C Yellow No. 5 & No. 6 color additives in this product though they primarily affect those who are allergic to aspirin.

Serum creatinine elevation occurs but it remains reversible and does not harm renal function; healthcare providers must use alternative renal function evaluation methods.

The therapy produces fetal harm so effective contraception must be used throughout treatment and during the post-treatment period.

Pregnancy / Lactation

Pregnancy warnings:

Pregnancy Category: It is not recommended during pregnancy as it may cause fetal harm.

Lactation:

Excretion of the drug in human breast milk is unknown

Pregnancy Categories: 

Category A: Satisfactory and well-controlled studies show no evidence of risk to the fetus in the 1^st trimester or in the 3^rd trimester.

Category B: No evidence of risk to fetus found in animal reproduction studies and there are not enough studies on pregnant women.

Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for an effect in humans, care must be taken for potential risks in pregnant women.

Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite potential risks may be used only in emergency cases for potential benefits.

Category X: Drugs listed in this category clearly outweigh risks over benefits. These category drugs should be prohibited for pregnant women.

Category N: There is no data available for the drug under this category.

Pharmacology

Pharmacology:

Vimseltinib (DCC-3014) represents an oral switch-control tyrosine kinase inhibitor which targets the regulatory switch-control region of colony-stimulating factor 1 receptor (CSF1R) for precise and potent inhibition.

Preclinical trials established that vimseltinib provided prolonged CSF1R activity suppression across both cell culture experiments and animal studies. The substance successfully eliminated macrophages and other CSF1R-dependent cells through its mechanism which stopped tumors from growing and prevented bone deterioration within mouse cancer models.

The confirmed translation between biomarker measurements and CSF1R inhibition together with decreased tumor mass emerged in Phase I study subjects with tenosynovial giant cell tumor (TGCT).

Pharmacodynamics:

Through its selective action on CSF1R vimseltinib implements an inhibitor action to block autophosphorylation signaling pathways which leads to reduced CSF1R-dependent cell multiplication of tumor-associated macrophages as well as tumor regression and inhibits bone degeneration particularly in tenosynovial giant cell tumor (TGCT). The drug produces favorable outcomes toward tumor reduction while controlling destructive bone processes mainly in cases of tenosynovial giant cell tumor (TGCT). Vimseltinib produced biomarker modulation through CSF1R inhibition during clinical trials which showed decreased tumor volume.

Pharmacokinetics:

Absorption

The maximum steady-state concentration of vimseltinib in patients reaches 747 ng/mL while the median time to reach this peak occurs within 1 hour (0.5 to 4 hours range). At steady state vimseltinib achieves an AUC of 13,400 ng⋅hr/mL.

Pharmacokinetic changes following food consumption remain within acceptable levels despite the consumption of high-fat meals containing 800–1000 kcal with 50% fat content.

Distribution

Vd of 90 L describes the drug’s distribution volume while human plasma proteins bind 96.5% of it.

Metabolism

Primary metabolic pathways of Vimseltinib proceed through oxidation combined with N-demethylation and N-dealkylation mechanisms. The breakdown of vimseltinib involves N-demethylation as its primary metabolic step alongside dehydrogenation and oxidation as its secondary processes. The drug shows no significant role as CYP450 enzymes do not participate in its metabolic breakdown.

Elimination and Excretion

Half-life: ~6 days

Clearance: 0.5 L/hr

After a single radiolabeled dose, vimseltinib is eliminated as follows:

• Feces: ~43% of the dose (9.1% unchanged)
• Urine: 38% of the dose (5.1% unchanged)

Adminstartion

Administration:

Take with or without food. Swallow whole; do not crush, break, or chew. Maintain a 72-hour interval between doses and follow the blister pack schedule.

Missed Dose:

≤48 hours: Take as soon as possible and resume the schedule.

>48 hours: Skip and take the next dose as scheduled.

Patient Information Leaflet

Patient information leaflet

Generic Name: vimseltinib

Why do we use vimseltinib?

Vimseltinib treats tenosynovial giant cell tumor (TGCT) in surgical ineligible patients who experience debilitating symptoms that restrict their functional abilities. The therapy functions by specifically blocking CSF1R pathways to diminish tumor-associated macrophages and hence delay the progression of the disease.