LUMVOA Solution for injection Ref.[116700] Active ingredients: Veligrotug

5.1 Infusion Reactions

LUMVOA may cause infusion reactions. Infusion reactions have been reported in approximately 9% of patients treated with LUMVOA. Signs and symptoms of infusion-related reactions include transient increases in blood pressure, fever, chills, headache, and fatigue. Infusion reactions may occur during or soon after an infusion. Reported infusion reactions are usually mild or moderate in severity and can usually be successfully managed with corticosteroids, antihistamines, and antipyretics. In patients who experience an infusion reaction, consideration should be given to standard premedication and/or administering infusions at a slower infusion rate.

5.2 Inflammatory Bowel Disease

LUMVOA may cause an exacerbation of inflammatory bowel disease (IBD). IBD has been reported in some patients receiving insulin-like growth factor-1 receptor inhibitors without a prior diagnosis of IBD. Monitor patients for signs and symptoms of IBD, including patients without a history of IBD. If IBD is suspected, discontinue use of LUMVOA.

5.3 Hyperglycemia

Hyperglycemia or increased blood glucose may occur in patients treated with LUMVOA. In clinical trials, 12% of patients, of whom one half had pre-existing diabetes or impaired glucose tolerance, experienced hyperglycemia. Hyperglycemic events should be controlled with medications for glycemic control, if necessary. Assess patients for elevated blood glucose and symptoms of hyperglycemia prior to infusion and continue to monitor while on treatment with LUMVOA. Ensure patients with hyperglycemia or preexisting diabetes are under appropriate glycemic control before and while receiving LUMVOA. Continue monitoring after treatment for patients who experience hyperglycemia while on LUMVOA.

5.4 Hearing Impairment Including Hearing Loss

LUMVOA may cause severe hearing impairment including hearing loss, which in some cases may be permanent. Assess patients' hearing before, during, and after treatment with LUMVOA and consider the benefit-risk of treatment with patients.

The following clinically significant adverse reactions are described elsewhere in the labeling:

• Infusion Reactions [see Warnings and Precautions (5.1)]
• Inflammatory Bowel Disease [see Warnings and Precautions (5.2)]
• Hyperglycemia [see Warnings and Precautions (5.3)]
• Hearing Impairment [see Warnings and Precautions (5.4)]

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 LUMVOA 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 LUMVOA and 38 received placebo) and 188 patients with chronic thyroid eye disease (125 received LUMVOA and 63 received placebo). Patients were treated with LUMVOA 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 LUMVOA patients and 99% of placebo patients).

The most common adverse reactions (≥5%) that occurred at greater incidence in the LUMVOA group than in the control group during the treatment period of Studies 1 and 2 are summarized in Table 1. 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 LUMVOA compared to 6% (2/33) of patients treated with placebo in the clinical trials.

Table 1. Adverse Reactions Occurring in 5% or More of Patients Treated with LUMVOA 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 LUMVOA were alopecia and onychoclasis (5%). Immune thrombocytopenia was also reported in one patient.

The observed incidence of anti-drug antibodies (ADA) is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of ADA in the studies described below with the incidence of ADA in other studies, including those of LUMVOA or of other veligrotug products.

In controlled clinical studies with veligrotug, ADA sampling was conducted during the 15-week treatment period, as well as during the post treatment follow-up period 12 weeks after the final infusion. Two hundred and ninety (290) of 361 patients (80.3%) had evaluable samples for ADA assessment, in which treatment emergent anti-veligrotug antibodies were detected in 20% (58/290) of patients. In general, there was no apparent correlation of anti-veligrotug antibody development with changes in the pharmacokinetics, safety, and/or effectiveness of veligrotug.

Risk Summary

Because inhibiting insulin-like growth factor-1 receptor (IGF-1R) signaling impacts embryonic development and placental development and function, LUMVOA may cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)].

There is insufficient data with LUMVOA 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 LUMVOA. Advise pregnant women and females of reproductive potential of the potential risk to a fetus.

LUMVOA 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 LUMVOA. Women of childbearing potential should have a pregnancy test performed by their doctor before starting treatment with LUMVOA. If the patient becomes pregnant during treatment, LUMVOA 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.

Risk Summary

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

Contraception

Females

Because inhibiting IGF-1R signaling impacts normal embryonic development and placental development and function, LUMVOA may cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)]. Advise females of reproductive potential to use effective contraception prior to initiation, during treatment with LUMVOA and for 6 months after the last dose of LUMVOA.

The safety and effectiveness of LUMVOA have not been established in pediatric patients.

Of the 301 patients in Study 1 and Study 2, 12% were 65 years of age or older, with a similar proportion of patients 65 years of age or older between treatment groups. No overall differences in safety or effectiveness of LUMVOA have been observed between patients 65 years of age or older and younger adult patients.