Veligrotug

Because inhibiting insulin-like growth factor-1 receptor (IGF-1R) signaling impacts embryonic development and placental development and function, veligrotug may cause fetal harm when administered to a pregnant woman.

There is insufficient data with veligrotug use in pregnant women to inform any drug associated risks for adverse developmental outcomes. Animal reproductive and developmental toxicity studies have not been conducted with veligrotug. Advise pregnant women and females of reproductive potential of the potential risk to a fetus.

Veligrotug should not be used during pregnancy, and appropriate forms of contraception should be implemented prior to initiation, during treatment and for 6 months after the last dose of veligrotug. Women of childbearing potential should have a pregnancy test performed by their doctor before starting treatment with veligrotug. If the patient becomes pregnant during treatment, veligrotug should be discontinued and the patient advised of the potential risk to the fetus.

The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

There is no information regarding the presence of veligrotug in human milk, the effects on the breast-fed infant or the effects on milk production.

Carcinogenesis

The carcinogenic potential of veligrotug has not been evaluated in long-term animal studies.

Mutagenesis

The genotoxic potential of veligrotug has not been evaluated.

Impairment of Fertility

Dedicated fertility studies have not been performed with veligrotug. In the repeat-dose toxicology studies in sexually mature male and female cynomolgus monkeys, no effects on the reproductive system were observed at exposure higher (7-fold) than the human exposure (AUC) at the maximum recommended human dose.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of veligrotug was evaluated in two randomized, double-masked, placebo-controlled clinical studies (Study 1 [NCT05176639] and Study 2 [NCT06021054]) consisting of 113 patients with active thyroid eye disease (75 received veligrotug and 38 received placebo) and 188 patients with chronic thyroid eye disease (125 received veligrotug and 63 received placebo). Patients were treated with veligrotug 10 mg/kg or placebo given as an intravenous infusion every 3 weeks for a total of 5 infusions. The majority of patients completed 5 infusions (94% of veligrotug patients and 99% of placebo patients).

The most common adverse reactions (≥5%) that occurred at greater incidence in the veligrotug group than in the control group during the treatment period of Studies 1 and 2 are summarized in the table below. In addition, menstrual disorders (amenorrhea, menstruation irregular, dysmenorrhea, menstruation delayed, intermenstrual bleeding, and menstrual disorder) were reported in approximately 29% (24/82) of menstruating women treated with veligrotug compared to 6% (2/33) of patients treated with placebo in the clinical trials.

Adverse Reactions Occurring in 5% or More of Patients Treated with Veligrotug and Greater Incidence than Placebo in Study 1 and Study 2:

¹ Hearing impairment includes tinnitus, hypoacusis, deafness, and autophony.
² Hyperglycemia includes blood glucose increased, glucose tolerance impaired, glycosylated hemoglobin increased, diabetes mellitus, glucose urine present, and impaired fasting glucose.
³ Fatigue includes asthenia.
⁴ Ear discomfort includes ear feels clogged or blocked, ear plugging, sensation of ear pressure, and ear popping.

During the follow-up period, the most common adverse reactions in patients treated with veligrotug were alopecia and onychoclasis (5%). Immune thrombocytopenia was also reported in one patient.