•
`•
`•
`
`HIGHLIGHTS OF PRESCRIBING INFORMATION
`These highlights do not include all the information needed to use
`TALTZ safely and effectively. See full prescribing information for
`TALTZ.
`TALTZ (ixekizumab) injection, for subcutaneous use
`Initial U.S. Approval: 2016
` --------------------------- RECENT MAJOR CHANGES --------------------------
`Dosage and Administration:
`05/2022
`Testing and Procedures Prior to Treatment Initiation (2.1)
` ---------------------------- INDICATIONS AND USAGE ---------------------------
`TALTZ® is a humanized interleukin-17A antagonist indicated for the
`treatment of:
`•
`patients aged 6 years or older with moderate-to-severe plaque
`psoriasis who are candidates for systemic therapy or phototherapy.
`(1.1)
`adults with active psoriatic arthritis. (1.2)
`adults with active ankylosing spondylitis. (1.3)
`adults with active non-radiographic axial spondyloarthritis with
`objective signs of inflammation. (1.4)
` ------------------------ DOSAGE AND ADMINISTRATION -----------------------
`Administer by subcutaneous injection.
`Adult Plaque Psoriasis (2.2)
`• Recommended dosage is 160 mg (two 80 mg injections) at Week
`0, followed by 80 mg at Weeks 2, 4, 6, 8, 10, and 12, then 80 mg
`every 4 weeks.
`Pediatric Plaque Psoriasis (2.3)
`• For patients weighing greater than 50 kg, recommended dosage is
`160 mg (two 80 mg injections) at Week 0, followed by 80 mg every
`4 weeks.
`• For patients weighing 25-50 kg, recommended dosage is 80 mg at
`Week 0, followed by 40 mg every 4 weeks.
`• For patients weighing less than 25 kg, recommended dosage is
`40 mg at Week 0, followed by 20 mg every 4 weeks.
`Psoriatic Arthritis (2.4)
`• Recommended dosage is 160 mg by subcutaneous injection (two
`80 mg injections) at Week 0, followed by 80 mg every 4 weeks.
`• For psoriatic arthritis patients with coexistent moderate-to-severe
`plaque psoriasis, use the dosing regimen for adult plaque
`psoriasis. (2.2)
`• TALTZ may be administered alone or in combination with a
`conventional DMARD (e.g., methotrexate).
`
`FULL PRESCRIBING INFORMATION: CONTENTS*
`1
`INDICATIONS AND USAGE
`1.1 Plaque Psoriasis
`1.2 Psoriatic Arthritis
`1.3 Ankylosing Spondylitis
`1.4 Non-radiographic Axial Spondyloarthritis
`2 DOSAGE AND ADMINISTRATION
`2.1 Testing and Procedures Prior to Treatment Initiation
`2.2 Adult Plaque Psoriasis
`2.3 Pediatric Plaque Psoriasis
`2.4 Psoriatic Arthritis
`2.5 Ankylosing Spondylitis
`2.6 Non-radiographic Axial Spondyloarthritis
`2.7
`Important Administration Instructions
`3 DOSAGE FORMS AND STRENGTHS
`4 CONTRAINDICATIONS
`5 WARNINGS AND PRECAUTIONS
`5.1
`Infections
`5.2 Pre-treatment Evaluation for Tuberculosis
`5.3 Hypersensitivity
`5.4
`Inflammatory Bowel Disease
`5.5
`Immunizations
`6 ADVERSE REACTIONS
`6.1 Clinical Trials Experience
`6.2
`Immunogenicity
`6.3 Postmarketing Experience
`
`
`
`
`
`Reference ID: 5019857
`
`1
`
`Ankylosing Spondylitis (2.5)
`• Recommended dosage is 160 mg by subcutaneous injection (two
`80 mg injections) at Week 0, followed by 80 mg every 4 weeks.
`Non-radiographic Axial Spondyloarthritis (2.6)
`• Recommended dosage is 80 mg by subcutaneous injection every
`4 weeks.
` ---------------------- DOSAGE FORMS AND STRENGTHS ---------------------
`Autoinjector
`•
`Injection: 80 mg/mL solution in a single-dose prefilled autoinjector.
`(3)
`Prefilled Syringe
`•
`Injection: 80 mg/mL solution in a single-dose prefilled syringe. (3)
` ------------------------------- CONTRAINDICATIONS ------------------------------
`Serious hypersensitivity reaction to ixekizumab or to any of the
`excipients. (4)
` ------------------------ WARNINGS AND PRECAUTIONS -----------------------
`•
`Infections: Serious infections have occurred. Instruct patients to
`seek medical advice if signs or symptoms of clinically important
`chronic or acute infection occur. If a serious infection develops,
`discontinue TALTZ until the infection resolves. (5.1)
`• Tuberculosis (TB): Evaluate for TB prior to initiating treatment.
`(5.2)
`• Hypersensitivity: If a serious allergic reaction occurs, discontinue
`TALTZ immediately and initiate appropriate therapy. (5.3)
`Inflammatory Bowel Disease: Crohn’s disease and ulcerative
`colitis, including exacerbations, occurred during clinical trials.
`Monitor closely when prescribing TALTZ to patients with
`inflammatory bowel disease (IBD). Discontinue TALTZ and initiate
`appropriate medical management if IBD develops. (5.4)
`Immunizations: Avoid use of live vaccines. (5.5)
`•
` ------------------------------- ADVERSE REACTIONS ------------------------------
`Most common (≥1%) adverse reactions associated with TALTZ
`treatment are injection site reactions, upper respiratory tract infections,
`nausea, and tinea infections. (6.1)
`To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly
`and Company at 1-800-545-5979 (1-800-LillyRx) or FDA at
`1-800-FDA-1088 or www.fda.gov/medwatch.
`See 17 for PATIENT COUNSELING INFORMATION and FDA-
`approved Medication Guide.
`
`•
`
`Revised: 07/2022
`
`8 USE IN SPECIFIC POPULATIONS
`8.1 Pregnancy
`8.2 Lactation
`8.4 Pediatric Use
`8.5 Geriatric Use
`11 DESCRIPTION
`12 CLINICAL PHARMACOLOGY
`12.1 Mechanism of Action
`12.2 Pharmacodynamics
`12.3 Pharmacokinetics
`13 NONCLINICAL TOXICOLOGY
`13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
`14 CLINICAL STUDIES
`14.1 Adult Plaque Psoriasis
`14.2 Pediatric Plaque Psoriasis
`14.3 Psoriatic Arthritis
`14.4 Ankylosing Spondylitis
`14.5 Non-radiographic Axial Spondyloarthritis
`16 HOW SUPPLIED/STORAGE AND HANDLING
`16.1 How Supplied
`16.2 Storage and Handling
`17 PATIENT COUNSELING INFORMATION
`*Sections or subsections omitted from the full prescribing information
`are not listed.
`
`
`
`
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`

`

`2
`
`FULL PRESCRIBING INFORMATION
`1
`INDICATIONS AND USAGE
`1.1
`Plaque Psoriasis
`TALTZ® is indicated for the treatment of patients 6 years of age and older with moderate-to-severe plaque
`psoriasis who are candidates for systemic therapy or phototherapy.
`1.2
`Psoriatic Arthritis
`TALTZ is indicated for the treatment of adult patients with active psoriatic arthritis.
`Ankylosing Spondylitis
`TALTZ is indicated for the treatment of adult patients with active ankylosing spondylitis.
`Non-radiographic Axial Spondyloarthritis
`TALTZ is indicated for the treatment of adult patients with active non-radiographic axial spondyloarthritis (nr-
`axSpA) with objective signs of inflammation.
`2
`DOSAGE AND ADMINISTRATION
`2.1
`Testing and Procedures Prior to Treatment Initiation
`Perform the following evaluations prior to TALTZ initiation:
`• Evaluate patients for tuberculosis (TB) infection. TALTZ initiation is not recommended in patients with
`active TB infection. Initiate treatment of latent TB prior to initiation of TALTZ [see Warnings and
`Precautions (5.2)].
`• Complete all age-appropriate vaccinations as recommended by current immunization guidelines prior to
`initiating treatment with TALTZ [see Warnings and Precautions (5.5)].
`Adult Plaque Psoriasis
`TALTZ is administered by subcutaneous injection. The recommended dosage is 160 mg (two 80 mg injections) at
`Week 0, followed by 80 mg at Weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.
`2.3
`Pediatric Plaque Psoriasis
`TALTZ is administered by subcutaneous injection every 4 weeks (Q4W). The recommended dosage in pediatric
`patients from 6 to less than 18 years of age with moderate-to-severe plaque psoriasis is based on the following weight
`categories.
`
`
`1.3
`
`1.4
`
`2.2
`
`Table 1: Recommended Dosing and Administration for Pediatric Patients
`Pediatric Patient’s Weight
`Starting Dose (Week 0)
`Dose every 4 weeks (Q4W) Thereafter
`Greater than 50 kg
`160 mg (two 80 mg injections)
`80 mg
`25 to 50 kg
`80 mg
`40 mg
`Less than 25 kg
`40 mg
`20 mg
`
`Psoriatic Arthritis
`The recommended dosage is 160 mg by subcutaneous injection (two 80 mg injections) at Week 0, followed by
`80 mg every 4 weeks.
`For psoriatic arthritis patients with coexistent moderate-to-severe plaque psoriasis, use the dosing regimen for
`adult plaque psoriasis [see Dosage and Administration (2.2)].
`TALTZ may be administered alone or in combination with a conventional disease-modifying antirheumatic drug
`(cDMARD) (e.g., methotrexate).
`2.5
`Ankylosing Spondylitis
`The recommended dosage is 160 mg by subcutaneous injection (two 80 mg injections) at Week 0, followed by
`80 mg every 4 weeks.
`2.6
`Non-radiographic Axial Spondyloarthritis
`The recommended dosage is 80 mg by subcutaneous injection every 4 weeks.
`Important Administration Instructions
`TALTZ is intended for use under the guidance and supervision of a physician. Adult patients may self-inject or
`caregivers may give injections of TALTZ 80 mg after training in subcutaneous injection technique using the autoinjector or
`prefilled syringe. Caregivers may give injections of TALTZ 80 mg to pediatric patients weighing more than 50 kg using the
`autoinjector or prefilled syringe after training and demonstration of proper subcutaneous injection technique.
`
`2.4
`
`2.7
`
`
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`
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`Reference ID: 5019857
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`3
`
`The TALTZ “Instructions for Use” contains more detailed instructions on the preparation and administration of
`TALTZ [see Instructions for Use].
`Before injection, remove TALTZ autoinjector or TALTZ prefilled syringe from the refrigerator and allow TALTZ to
`reach room temperature (30 minutes) without removing the needle cap. Inspect TALTZ visually for particulate matter and
`discoloration prior to administration. TALTZ is a clear and colorless to slightly yellow solution. Do not use if the liquid
`contains visible particles, is discolored or cloudy (other than clear and colorless to slightly yellow).
`Administer each injection at a different anatomic location (such as upper arms, thighs or any quadrant of
`abdomen) than the previous injection, and not into areas where the skin is tender, bruised, erythematous, indurated or
`affected by psoriasis. Administration of TALTZ in the upper, outer arm may be performed by a caregiver or healthcare
`provider [see Instructions for Use].
`TALTZ does not contain preservatives, therefore discard any unused product.
`If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled
`
`time.
`Pediatric Patients Weighing 50 kg or Less
`TALTZ doses of 20 mg or 40 mg [see Dosage and Administration (2.3)] must be prepared and administered by a
`qualified healthcare professional. Use only the commercial TALTZ 80 mg/1 mL prefilled syringe when preparing the
`prescribed 20 mg and 40 mg pediatric dose [see Instructions for Use].
`
`
`1. Gather the following necessary supplies for preparation:
`•
`0.5 mL or 1 mL disposable syringe
`• Sterile needle for withdrawal
`•
`27-gauge sterile needle for administration
`• Sterile, clear glass vial.
`2. Expel the entire contents of the prefilled syringe into the sterile vial. DO NOT shake or swirl the vial. No other
`medications should be added to solutions containing TALTZ.
`3. Using the 0.5 mL or 1 mL disposable syringe and sterile needle, withdraw the prescribed dose from the vial
`(0.25 mL for 20 mg; 0.5 mL for 40 mg).
`4. Remove the needle from the syringe and replace it with a 27-gauge needle prior to administering TALTZ to the
`patient.
`
`4
`
`
`Storage
`If necessary, the prepared TALTZ may be stored at room temperature for up to 4 hours from first puncturing the
`sterile vial.
`3
`DOSAGE FORMS AND STRENGTHS
`TALTZ is a clear and colorless to slightly yellow solution available as:
`Autoinjector
`•
`Injection: 80 mg/mL solution of TALTZ in a single-dose prefilled autoinjector
`Prefilled Syringe
`•
`Injection: 80 mg/mL solution of TALTZ in a single-dose prefilled syringe
`CONTRAINDICATIONS
`TALTZ is contraindicated in patients with a previous serious hypersensitivity reaction, such as anaphylaxis, to
`ixekizumab or to any of the excipients [see Warnings and Precautions (5.3)].
`5
`WARNINGS AND PRECAUTIONS
`5.1
`Infections
`TALTZ may increase the risk of infection. In clinical trials in adult patients with plaque psoriasis, the TALTZ group
`had a higher rate of infections than the placebo group (27% vs. 23%). Upper respiratory tract infections, oral candidiasis,
`conjunctivitis and tinea infections occurred more frequently in the TALTZ group than in the placebo group. A similar
`increase in risk of infection was seen in placebo-controlled trials in patients with pediatric psoriasis, psoriatic arthritis,
`ankylosing spondylitis, and non-radiographic axial spondyloarthritis [see Adverse Reactions (6.1)].
`Instruct patients treated with TALTZ to seek medical advice if signs or symptoms of clinically important chronic or
`acute infection occur. If a patient develops a serious infection or is not responding to standard therapy, monitor the patient
`closely and discontinue TALTZ until the infection resolves.
`5.2
`Pre-treatment Evaluation for Tuberculosis
`
`
`
`
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`Reference ID: 5019857
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`
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`

`

`Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with TALTZ. Do not administer to
`patients with active TB infection. Initiate treatment of latent TB prior to administering TALTZ. Consider anti-TB therapy
`prior to initiating TALTZ in patients with a past history of latent or active TB in whom an adequate course of treatment
`cannot be confirmed. Patients receiving TALTZ should be monitored closely for signs and symptoms of active TB during
`and after treatment.
`5.3
`Hypersensitivity
`Serious hypersensitivity reactions, including angioedema and urticaria (each ≤0.1%), occurred in the TALTZ group
`in clinical trials. Anaphylaxis, including cases leading to hospitalization, has been reported in post marketing use with
`TALTZ [see Adverse Reactions (6.1, 6.3)]. If a serious hypersensitivity reaction occurs, discontinue TALTZ immediately
`and initiate appropriate therapy.
`5.4
`Inflammatory Bowel Disease
`Patients treated with TALTZ may be at increased risk of inflammatory bowel disease. In clinical trials, Crohn’s
`disease and ulcerative colitis, including exacerbations, occurred at a greater frequency in the TALTZ group than the
`placebo control group [see Adverse Reactions (6.1)]. During TALTZ treatment, monitor for onset or exacerbation of
`inflammatory bowel disease and if IBD occurs, discontinue TALTZ and initiate appropriate medical management.
`5.5
`Immunizations
`Prior to initiating therapy with TALTZ, consider completion of all age-appropriate immunizations according to
`current immunization guidelines. Avoid use of live vaccines in patients treated with TALTZ. No data are available on the
`response to live vaccines.
`6
`ADVERSE REACTIONS
`The following adverse drug reactions are discussed in greater detail in other sections of the label:
`•
`Infections [see Warnings and Precautions (5.1)]
`• Hypersensitivity Reactions [see Contraindications (4) and Warnings and Precautions (5.3)]
`•
`Inflammatory Bowel Disease [see Warnings and Precautions (5.4)]
`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.
`
`Adult Plaque Psoriasis
`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 2 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 (14)].
`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 2 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 2: Adverse Reactions Occurring in ≥1% of the TALTZ Group and More Frequently than in the Placebo
`Group in the Plaque Psoriasis Clinical Trials through Week 12
`TALTZ 80 mg Q2W
`Etanerceptb
`(N=1167) n (%)
`(N=287) n (%)
`Injection site reactions
`196 (17)
`32 (11)
`Upper respiratory tract infectionsa
`163 (14)
`23 (8)
`Nausea
`23 (2)
`1 (<1)
`Tinea infections
`17 (2)
`0
`a Upper respiratory tract infections cluster includes nasopharyngitis and rhinovirus infection.
`b U.S. approved etanercept.
`
`
`6.1
`
`Adverse Reactions
`
`4
`
`Placebo
`(N=791) n (%)
`26 (3)
`101 (13)
`5 (1)
`1 (<1)
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`Reference ID: 5019857
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`5
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`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
`Injection Site Reactions
`The most frequent injection site reactions were erythema and pain. Most injection site reactions were mild-to-
`moderate in severity and did not lead to discontinuation of TALTZ.
`Infections
`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 (5.1)].
`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).
`Inflammatory Bowel Disease
`In adult subjects with plaque psoriasis, Crohn’s disease and ulcerative colitis, including exacerbations, occurred at
`a greater frequency in the TALTZ 80 mg Q2W group (Crohn’s disease 0.1%, ulcerative colitis 0.2%) than the placebo
`group (0%) during the 12-week, placebo-controlled period in clinical trials [see Warnings and Precautions (5.4)].
`Laboratory Assessment of Cytopenia
`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
`
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`6
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`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.
`
`Pediatric Plaque Psoriasis
`TALTZ was evaluated in a placebo-controlled trial in pediatric subjects with moderate-to-severe psoriasis 6 to less
`than 18 years of age. A total of 171 subjects were studied (115 subjects on TALTZ and 56 subjects on placebo). Overall,
`the safety profile observed in pediatric subjects with plaque psoriasis treated with TALTZ every 4 weeks is consistent with
`the safety profile in adult subjects with plaque psoriasis with the exception of the frequencies of conjunctivitis (2.6%),
`influenza (1.7%), and urticaria (1.7%).
`In this clinical trial, Crohn’s disease occurred at a greater frequency in the TALTZ group (0.9%) than the placebo
`group (0%) during the 12-week, placebo-controlled period. Crohn’s disease occurred in a total of 4 TALTZ treated
`subjects (2.0%) in the clinical trial [see Warnings and Precautions (5.4)].
`
`Psoriatic Arthritis
`TALTZ was studied in two placebo-controlled trials in patients with psoriatic arthritis. A total of 678 patients were
`studied (454 patients on TALTZ and 224 on placebo). A total of 229 patients in these trials received TALTZ 160 mg at
`Week 0, followed by 80 mg every 4 weeks (Q4W). Overall, the safety profile observed in patients with psoriatic arthritis
`treated with TALTZ Q4W is consistent with the safety profile in adult patients with plaque psoriasis with the exception of
`the frequencies of influenza (1.3%) and conjunctivitis (1.3%).
`
`Ankylosing Spondylitis
`TALTZ was studied in two placebo-controlled trials in patients with ankylosing spondylitis. A total of 566 patients
`were studied (376 patients on TALTZ and 190 on placebo). A total of 195 patients in these trials received TALTZ 80 or
`160 mg at Week 0, followed by 80 mg every 4 weeks (Q4W). Overall, the safety profile observed in patients with
`ankylosing spondylitis treated with TALTZ Q4W is consistent with the safety profile in adult patients with plaque psoriasis.
`In adult patients with ankylosing spondylitis, Crohn’s disease and ulcerative colitis, including exacerbations,
`occurred in 2 patients (1.0%) and 1 patient (0.5%), respectively, in the TALTZ 80 mg Q4W group and 1 patient (0.5%) and
`0%, respectively, in the placebo group during the 16-week, placebo-controlled period in clinical trials. Of these patients,
`serious events occurred in 1 patient in the TALTZ 80 mg Q4W group and 1 patient in the placebo group [see Warnings
`and Precautions (5.4)].
`
`Non-radiographic Axial Spondyloarthritis
`TALTZ was studied in a placebo-controlled trial in patients with non-radiographic axial spondyloarthritis. A total of
`303 patients were studied (198 patients on TALTZ and 105 on placebo). A total of 96 patients in this trial received TALTZ
`80 or 160 mg at Week 0, followed by 80 mg every 4 weeks (Q4W). Overall, the safety profile observed in patients with
`non-radiographic axial spondyloarthritis treated with TALTZ 80 mg Q4W up to Week 16 is consistent with the previous
`experience of TALTZ in other indications.
`6.2
`Immunogenicity
`As with all therapeutic proteins there is the potential for immunogenicity with TALTZ. 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.
`
`Plaque Psoriasis Population
`By Week 12, approximately 9% of adult 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 adult 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.
`In pediatric psoriasis subjects treated with ixekizumab at the recommended dosing regimen up to 12 weeks,
`21 subjects (18%) developed anti-drug antibodies, 5 subjects (4%) had confirmed neutralizing antibodies associated with
`low drug concentrations. No conclusive evidence could be obtained on the potential association of neutralizing antibodies
`and clinical response and/or adverse events due to small number of pediatric subjects in the study.
`
`Psoriatic Arthritis Population
`
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`Reference ID: 5019857
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`7
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`8
`8.1
`
`For subjects treated with TALTZ 80 mg every 4 weeks for up to 52 weeks (PsA1), 11% developed anti-drug
`antibodies, and 8% had confirmed neutralizing antibodies.
`
`Ankylosing Spondylitis Population
`For patients treated with TALTZ 80 mg every 4 weeks for up to 16 weeks (AS1, AS2), 5.2% developed anti-drug
`antibodies, and 1.5% had neutralizing antibodies.
`
`Non-radiographic Axial Spondyloarthritis Population
`Of patients treated with TALTZ 80 mg every 4 weeks for up to 52 weeks (nr-axSpA1), 8.9% developed anti-drug
`antibodies, all of which were low titer. No patient had neutralizing antibodies.
`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 across indications or with the
`incidences of antibodies to other products may be misleading.
`6.3
`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 (4) and Warnings and Precautions (5.3)].
`USE IN SPECIFIC POPULATIONS
`Pregnancy
`Pregnancy Exposure Registry
`There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to TALTZ during
`pregnancy. Pregnant women exposed to TALTZ are encouraged to enroll in the TALTZ Pregnancy Registry by calling
`1-800-284-1695. Contact information for the registry is also available on https://www.taltz.com.
`
`Risk Summary
`Available data from the published literature and the pharmacovigilance database with TALTZ use in pregnant
`women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal
`or fetal outcomes.
`Human IgG is known to cross the placental barrier; therefore, TALTZ may be transmitted from the mother to the
`developing fetus. An embryofetal development study conducted in pregnant monkeys during organogenesis at doses up
`to 19 times the maximum recommended human dose (MRHD) revealed no evidence of harm to the developing fetus.
`When dosing was continued until parturition, neonatal deaths were observed at 1.9 times the MRHD [see Data]. The
`clinical significance of these nonclinical findings is unknown.
`The background risk of major birth defects and miscarriage for the indicated population is unknown. All
`pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the
`estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to
`20%, respectively.
`Data
`Animal Data
`An embryofetal development study was conducted in cynomolgus monkeys administered ixekizumab. No
`malformations or embryofetal toxicity were observed in fetuses from pregnant monkeys administered ixekizumab weekly
`by subcutaneous injection during organogenesis to near parturition at doses up to 19 times the MRHD (on a mg/kg basis
`of 50 mg/kg/week). Ixekizumab crossed the placenta in monkeys.
`In a pre- and post-natal development toxicity study, pregnant cynomolgus monkeys were administered weekly
`subcutaneous doses of ixekizumab up to 19 times the MRHD from the beginning of organogenesis to parturition. Neonatal
`deaths occurred in the offspring of two monkeys administered ixekizumab at 1.9 times the MRHD (on a mg/kg basis of
`5 mg/kg/week) and two monkeys administered ixekizumab at 19 times the MRHD (on a mg/kg basis of 50 mg/kg/week).
`These neonatal deaths were attributed to early delivery, trauma, or congenital defect. The clinical significance of these
`findings is unknown. No ixekizumab-related effects on functional or immunological development were observed in the
`surviving infants from birth through 6 months of age.
`8.2
`Lactation
`Risk Summary
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`Reference ID: 5019857
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`There are no available data on the presence of ixekizumab in human milk, the effects on the breastfed infant, or
`the effects on milk production. Ixekizumab was detected in the milk of lactating cynomolgus monkeys. When a drug is
`present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of
`breastfeeding should be considered along with the mother’s clinical need for TALTZ and any potential adverse effects on
`the breastfed infant from TALTZ or from the underlying maternal condition.
`8.4
`Pediatric Use
`The safety and effectiveness of TALTZ have been established in pediatric subjects aged 6 years to less than 18
`years with moderate-to-severe plaque psoriasis. The safety and effectiveness of TALTZ in other pediatric indications and
`for pediatric subjects less than 6 years of age have not been established.
`8.5
`Geriatric Use
`Of the 4204 adult psoriasis subjects exposed to TALTZ, a total of 301 were 65 years or older, and 36 subjects
`were 75 years or older. Although no differences in safety or efficacy were observed between older and younger subjects,
`the number of subjects aged 65 and over is not sufficient to determine whether they respond differently from younger
`subjects [see Clinical Pharmacology (12.3)].
`11
`DESCRIPTION
`Ixekizumab is a humanized immunoglobulin G subclass 4 (IgG4) monoclonal antibody (mAb) with neutralizing
`activity against IL-17A. Ixekizumab is produced by recombinant DNA technology in a recombinant mammalian cell line
`and purified using stand