Summary of the safety profile The safety of ROMVIMZA is based on pooled data from 184 patients with TGCT who received ROMVIMZA at a dose of 30 mg twice weekly in 2 clinical studies. The MOTION study, a phase 3, 7 double-blind, multicentre, randomised (2:1), placebo-controlled study, included 122 adult patients who received vimseltinib (n = 83) or placebo (n = 39) in the double-blind period; 35 patients crossed over from placebo and received vimseltinib in the open-label period.
The phase 1/2 study DCC-3014-01-001 included a total of 66 patients with TGCT who received vimseltinib at a dose of 30 mg twice weekly. The median duration of treatment in the pooled safety population was 13 months. The median age of patients who received vimseltinib was 44 years (range from 20 to 78 years) and the population was 60% female and 72% White.
The most frequently observed adverse reactions were increased aspartate aminotransferase (AST) (92%), periorbital oedema (63%), increased cholesterol (53%), rash (51%), increased creatinine (43%), decreased neutrophils (36%), fatigue (30%), face oedema (28%), increased alanine aminotransferase (ALT) (27%), pruritus (27%), peripheral oedema (22%) and hypertension (21%).
5%). 5%). Permanent discontinuation due to an adverse reaction occurred in 7% of patients. The most frequently observed adverse reactions leading to permanent discontinuation were rash (3%), periorbital oedema (2%), neuropathy (1%) and pruritus (1%).
Dose reductions or interruptions due to an adverse reaction occurred in 59% of patients. The most frequently observed adverse reactions leading to dose reductions or interruptions were rash (21%), periorbital oedema (18%), increased creatine phosphokinase (CPK) (17%), pruritus (10%), face oedema (7%), generalised oedema (7%), fatigue (6%) and peripheral oedema (5%).
Tabulated list of adverse reactions The adverse reactions are listed below by system organ class and frequency categories, defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), rare (≥ 1/10 000 to < 1/1 000), very rare (< 1/10 000), not known (cannot be estimated from the available data).
Within each frequency category, adverse reactions are presented in order of decreasing seriousness.
Table 2:
Adverse reactions observed in MOTION and DCC-3014-01-001 studies System organ class Frequency category Adverse reaction Nervous system disorders Very common Neuropathy1 Eye disorders Very common Periorbital oedema2, lacrimation increased Common Dry eye, vision blurred Vascular disorders Very common Hypertension Skin and subcutaneous tissue disorders Very common Rash3, pruritus, dry skin General disorders and administration site conditions Very common Peripheral oedema, fatigue, face oedema, generalised oedema Investigations4 Very common Blood creatine phosphokinase increased5, aspartate aminotransferase increased, blood cholesterol increased, blood creatinine increased, neutrophil 8 System organ class Frequency category Adverse reaction count decreased, alanine aminotransferase increased, alkaline phosphatase increased 1 Neuropathy comprises peripheral neuropathy, paraesthesia, hypoaesthesia, peripheral sensory neuropathy.
2 Periorbital oedema comprises eye oedema, eyelid oedema, swelling of eyelid, periorbital oedema, periorbital swelling. 3 Rash comprises rash, rash erythematous, rash macular, rash maculo-papular, rash papular, rash pruritic, dermatitis acneiform, erythema.
4 Terms based on laboratory parameters. 5 Frequency category for blood creatine phosphokinase increased is based on laboratory data from DCC-3014-01-001 only. Description of selected adverse reactions Creatine phosphokinase (CPK) Consistent with the mechanism of action, increased CPK was reported during the MOTION study in vimseltinib-treated patients.
The frequency of increased CPK cannot be determined from the MOTION study because CPK was not assessed at baseline. In the phase 1/2 study conducted in 66 patients receiving vimseltinib 30 mg twice weekly, increased CPK was observed in all patients.
Other special populations Elderly No overall differences in safety were observed between patients ≥ 65 years of age and patients < 65 years of age. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.
It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.