Ixekizumab Injection, for Subcutaneous Use

TALTZ™ is indicated for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.

Included as part of the "PRECAUTIONS" Section

Advise the patient and/or caregiver to read the FDA-approved patient labeling (Medication Guide and Instructions for Use) before the patient starts using TALTZ, and each time the prescription is renewed, as there may be new information they need to know.

Instructions On Self-Administration

Provide guidance to patients and caregivers on proper subcutaneous injection technique, including aseptic technique, and how to use the autoinjector or prefilled syringe correctly [see Instructions for Use].

Infection

Inform patients that TALTZ may lower the ability of their immune system to fight infections. Instruct patients of the importance of communicating any history of infections to the healthcare provider, and contacting their healthcare provider if they develop any symptoms of infection [see WARNINGS AND PRECAUTIONS].

Allergic Reactions

Advise patients to seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions [see WARNINGS AND PRECAUTIONS].

The following adverse drug reactions are discussed in greater detail in other sections of the label:

• Infections [see WARNINGS AND PRECAUTIONS]
• Hypersensitivity Reactions [see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS]
• Inflammatory Bowel Disease [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying and controlled 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.

Weeks 0 To 12

Three placebo-controlled trials in subjects with plaque psoriasis were integrated to evaluate the safety of TALTZ compared to placebo for up to 12 weeks. A total of 1167 subjects (mean age 45 years; 66% men; 94% White) with plaque psoriasis received TALTZ (160 mg at Week 0, 80 mg every two weeks [Q2W] for 12 weeks) subcutaneously. In two of the trials, the safety of TALTZ (use up to 12 weeks) was also compared with an active comparator, U.S. approved etanercept [see Clinical Studies].

In the 12-week, placebo-controlled period, adverse events occurred in 58% of the TALTZ Q2W group (2.5 per subject-year of follow-up) compared with 47% of the placebo group (2.1 per subject-year of follow-up). Serious adverse events occurred in 2% of the TALTZ group (0.07 per subject-year of follow-up), and in 2% of the placebo group (0.07 per subject-year of follow-up).

Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the TALTZ group than in the placebo group during the 12-week placebo-controlled period of the pooled clinical trials.

Table 1: Adverse Reactions Occurring in ≥1% of the TALTZ Group and More Frequently than in the Placebo

Adverse reactions that occurred at rates less than 1% in the TALTZ group and more frequently than in the placebo group during the 12-week induction period included rhinitis, oral candidiasis, urticaria, influenza, conjunctivitis, inflammatory bowel disease, and angioedema.

Weeks 13 To 60

A total of 332 subjects received the recommended maintenance regimen of TALTZ 80 mg dosed every 4 weeks.

During the maintenance period (Weeks 13 to 60), adverse events occurred in 80% of subjects treated with TALTZ (1.0 per subject-year of follow-up) compared to 58% of subjects treated with placebo (1.1 per subject-year of follow-up).

Serious adverse events were reported in 4% of subjects treated with TALTZ (0.05 per subject-year of follow-up) and none in the subjects treated with placebo.

Weeks 0 To 60

Over the entire treatment period (Weeks 0 to 60), adverse events were reported in 67% of subjects treated with TALTZ (1.4 per subject-year of follow-up) compared to 48% of subjects treated with placebo (2.0 per subject-year of follow-up). Serious adverse events were reported in 3% of subjects treated with TALTZ (0.06 per subject-year of follow-up), and in 2% of subjects treated with placebo (0.06 per subject-year of follow-up).

Specific Adverse Drug Reactions

The most frequent injection site reactions were erythema and pain. Most injection site reactions were mild-tomoderate in severity and did not lead to discontinuation of TALTZ.

In the 12-week, placebo-controlled period of the clinical trials in plaque psoriasis, infections occurred in 27% of subjects treated with TALTZ (1.2 per subject-year of follow-up) compared to 23% of subjects treated with placebo (1.0 per subject-year of follow-up). Serious infections occurred in 0.4% of subjects treated with TALTZ (0.02 per subject-year of follow-up) and in 0.4% of subjects treated with placebo (0.02 per subject-year of follow-up) [see WARNINGS AND PRECAUTIONS].

During the maintenance treatment period (Weeks 13 to 60), infections occurred in 57% of subjects treated with TALTZ (0.70 per subject-year of follow-up) compared to 32% of subjects treated with placebo (0.61 per subject-year of follow-up). Serious infections occurred in 0.9% of subjects treated with TALTZ (0.01 per subject-year of follow-up) and none in the subjects treated with placebo.

Over the entire treatment period (Weeks 0 to 60), infections were reported in 38% of subjects treated with TALTZ (0.83 per subject-year of follow-up) compared to 23% of subjects treated with placebo (1.0 per subject-year of follow-up). Serious infections occurred in 0.7% of subjects treated with TALTZ (0.02 per subject-year of follow-up), and in 0.4% of subject treated with placebo (0.02 per subject-year of follow-up).

Neutropenia

Over the entire treatment period (Weeks 0 to 60), neutropenia occurred in 11% of subjects treated with TALTZ (0.24 per subject-year of follow-up) compared to 3% of subjects treated with placebo (0.14 per subject-year of follow-up). In subjects treated with TALTZ, the incidence rate of neutropenia during Weeks 13 to 60 was lower than the incidence rate during Weeks 0 to 12.

In the 12-week, placebo-controlled period, neutropenia ≥ Grade 3 (<1,000 cells/mm3) occurred in 0.2% of the TALTZ group (0.007 per subject-year of follow-up) compared to 0.1% of the placebo group (0.006 per subject-year of follow-up). The majority of cases of neutropenia were either Grade 2 (2% for TALTZ 80 mg Q2W versus 0.3% for placebo; ≥1,000 to <1,500 cells/mm3) or Grade 1 (7% for TALTZ 80 mg Q2W versus 3% for placebo; ≥1,500 cells/mm3 to .2,000 cells/mm3). Neutropenia in the TALTZ group was not associated with an increased rate of infection compared to the placebo group.

Thrombocytopenia

Ninety eight percent of cases of thrombocytopenia were Grade 1 (3% for TALTZ 80 mg Q2W versus 1% for placebo; ≥75,000 cells/mm3 to <150,000 cells/mm3). Thrombocytopenia in subjects treated with TALTZ was not associated with an increased rate of bleeding compared to subjects treated with placebo.

Active Comparator Trials

In the two clinical trials that included an active comparator, the rate of serious adverse events during weeks zero to twelve was 0.7% for U.S. approved etanercept and 2% for TALTZ 80 mg Q2W, and the rate of discontinuation from adverse events was 0.7% for U.S. approved etanercept and 2% for TALTZ 80 mg Q2W. The incidence of infections was 18% for U.S. approved etanercept and 26% for TALTZ 80 mg Q2W. The rate of serious infections was 0.3% for both TALTZ 80 mg Q2W and U.S. approved etanercept.

Immunogenicity

As with all therapeutic proteins there is the potential for immunogenicity with TALTZ. By Week 12, approximately 9% of subjects treated with TALTZ every 2 weeks developed antibodies to ixekizumab. Approximately 22% of subjects treated with TALTZ at the recommended dosing regimen developed antibodies to ixekizumab during the 60-week treatment period. The clinical effects of antibodies to ixekizumab are dependent on the antibody titer; higher antibody titers were associated with decreasing drug concentration and clinical response.

Of the subjects who developed antibodies to ixekizumab during the 60-week treatment period, approximately 10%, which equates to 2% of subjects treated with TALTZ at the recommended dosing regimen, had antibodies that were classified as neutralizing. Neutralizing antibodies were associated with reduced drug concentrations and loss of efficacy.

However, the assay to test for neutralizing antibodies has limitations detecting neutralizing antibodies in the presence of ixekizumab; therefore, the incidence of neutralizing antibodies development could be underestimated.

The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to TALTZ with the incidences of antibodies to other products may be misleading.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of TALTZ. Because the reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to TALTZ exposure.

Immune system disorders: anaphylaxis [see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS] .

Read the entire FDA prescribing information for Taltz (Ixekizumab Injection, for Subcutaneous Use)

• Psoriasis