Taltz

How Supplied

TALTZ injection is a sterile, preservative free, clear and colorless to slightly yellow solution available in:

• a single-dose prefilled autoinjector or a single-dose prefilled syringe to deliver 80 mg ixekizumab.
• a single-dose prefilled syringe to deliver 40 mg ixekizumab.
• a single-dose prefilled syringe to deliver 20 mg ixekizumab.

TALTZ is supplied as:

If the 20 mg/0.25 mL or 40 mg/0.5 mL prefilled syringe is unavailable, TALTZ doses of 20 mg or 40 mg for pediatric patients with plaque psoriasis [see Dosage and Administration (2.3)] must be manually prepared according to the steps below using only the TALTZ 80 mg/mL prefilled syringe. The preparation and administration of the 20 mg and 40 mg doses should only be performed by a qualified healthcare professional. For additional preparation and administration instructions, [see Dosage and Administration (2.7)].

• 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.
• Expel the entire contents of the prefilled syringe into the sterile vial. DO NOT shake or swirl the vial. Do not add other medications to solutions containing TALTZ.
• 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).
• Remove the needle from the syringe and replace it with a 27-gauge needle prior to administering TALTZ.

Storage of Prepared TALTZ

If necessary, TALTZ 20 mg or 40 mg doses prepared from an 80 mg/mL prefilled syringe may be stored at room temperature for up to 4 hours from first puncturing the sterile vial.

Storage and Handling

TALTZ is sterile and preservative-free. Discard any unused portion.

• TALTZ must be protected from light until use.
• Store refrigerated at 2°C to 8°C (36°F to 46°F).
  • If needed, patients/caregivers may store TALTZ at room temperature up to 30°C (86°F) for up to 5 days in the original carton to protect from light. Once TALTZ has been stored at room temperature, do not return to the refrigerator and discard, if unused, within 5 days.
  • Record the date when TALTZ is first removed from the refrigerator in the spaces provided on the carton.
  • For the 2 or 3 autoinjector pack, remove a single autoinjector at a time leaving the remaining autoinjector(s) in the original carton in the refrigerator. Ensure the unrefrigerated TALTZ is protected from light.
• Do not freeze. Do not use TALTZ if it has been frozen.
• Do not shake.
• Discard the TALTZ single-dose autoinjector or syringe after use in a puncture-resistant container.
• Not made with natural rubber latex.

Risk Summary

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.

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 standard technology for bioprocessing. Ixekizumab is comprised of two identical light chain polypeptides of 219 amino acids each and two identical heavy chain polypeptides of 445 amino acids each and has a molecular weight of 146,158 Daltons for the protein backbone of the molecule.

TALTZ injection is a sterile, preservative free, clear and colorless to slightly yellow solution, for subcutaneous use available as 80 mg of ixekizumab in a 1 mL single-dose prefilled autoinjector or a single-dose prefilled syringe, 40 mg of ixekizumab in a 0.5 mL single-dose prefilled syringe, or 20 mg of ixekizumab in a 0.25 mL single-dose prefilled syringe. The prefilled autoinjector and prefilled syringe each contain a 1 mL glass syringe with a fixed 27 gauge ½ inch needle. The TALTZ 80 mg prefilled autoinjector and prefilled syringe are manufactured to deliver 80 mg of ixekizumab. The TALTZ 40 mg prefilled syringe is manufactured to deliver 40 mg of ixekizumab. The TALTZ 20 mg prefilled syringe is manufactured to deliver 20 mg of ixekizumab.

Each TALTZ 80 mg/mL single-dose autoinjector or TALTZ 80 mg/mL single-dose prefilled syringe is composed of ixekizumab (80 mg); Polysorbate 80, USP (0.3 mg); Sucrose, USP (80 mg); and Water for Injection, USP. Sodium Hydroxide, USP-NF, may have been added to adjust pH. The TALTZ solution has a pH of 5.2 –  6.2.

Each TALTZ 40 mg/0.5 mL single-dose prefilled syringe is composed of ixekizumab (40 mg); Polysorbate 80, USP (0.15 mg); Sucrose, USP (40 mg); and Water for Injection, USP. Sodium Hydroxide, USP-NF, may have been added to adjust pH. The TALTZ solution has a pH of 5.2 –  6.2.

Each TALTZ 20 mg/0.25 mL single-dose prefilled syringe is composed of ixekizumab (20 mg); Polysorbate 80, USP (0.08 mg); Sucrose, USP (20 mg); and Water for Injection, USP. Sodium Hydroxide, USP-NF, may have been added to adjust pH. The TALTZ solution has a pH of 5.2 –  6.2.

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)].

In the postmarketing setting, serious bacterial, viral, and fungal opportunistic infections have been reported in patients receiving IL-17 inhibitors including TALTZ. 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.

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.

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.

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)].

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.

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)].

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)]
• Eczematous Eruptions [see Warnings and Precautions (5.4)]
• Inflammatory Bowel Disease [see Warnings and Precautions (5.5)]

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.

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.

No formal pharmacodynamic studies have been conducted with TALTZ.

The pharmacokinetic (PK) properties of ixekizumab were similar across the adult plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, and non-radiographic axial spondyloarthritis indications.

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)

TALTZ is indicated for the treatment of adult patients with active psoriatic arthritis.

Ixekizumab is a humanized IgG4 monoclonal antibody that selectively binds with the interleukin 17A (IL-17A) cytokine and inhibits its interaction with the IL-17 receptor. IL-17A is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Ixekizumab inhibits the release of proinflammatory cytokines and chemokines.

The safety and efficacy of TALTZ were assessed in 679 patients, in 2 randomized, double-blind, placebo-controlled studies (PsA1 and PsA2) in adult patients, age 18 years and older with active psoriatic arthritis (at least 3 swollen and at least 3 tender joints) despite non-steroidal anti-inflammatory drug (NSAID), corticosteroid or disease modifying anti-rheumatic drug (DMARD) therapy. Patients in these studies had a diagnosis of PsA for at least 6 months across both studies. At baseline, 60% and 23% of the patients had enthesitis and dactylitis, respectively. In PsA2, all patients discontinued previous treatment with anti-TNFα agents due to either inadequate response or intolerance. In addition, approximately 47% of patients from both studies had concomitant methotrexate (MTX) use.

PsA1 Study (NCT 01695239) evaluated 417 biologic-naive patients, who were treated with either TALTZ 160 mg at Week 0 followed by 80 mg every 2 weeks (Q2W) or 4 weeks (Q4W), adalimumab 40 mg every 2 weeks, or placebo. PsA2 Study (NCT 02349295) evaluated 363 anti-TNFα experienced patients, who were treated with TALTZ 160 mg at Week 0 followed by 80 mg every 2 or 4 weeks, or placebo. Patients receiving placebo were re-randomized to receive TALTZ (80 mg every 2 or 4 weeks) at Week 16 or Week 24 based on responder status. The primary endpoint was the percentage of patients achieving an ACR20 response at Week 24.

TALTZ is indicated for the treatment of adult patients with active ankylosing spondylitis.

• 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)
• Eczematous Eruptions: In the postmarketing setting, cases of severe eczematous eruptions were reported in patients receiving TALTZ. Treatment may need to be discontinued to resolve the eczematous eruption. (5.4)
• 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. (5.5)
• Immunizations: Avoid use of live vaccines. (5.6)

Three multicenter, randomized, double-blind, placebo-controlled trials, Trials 1, 2, and 3 (NCT 01474512, NCT 01597245, NCT 01646177), enrolled a total of 3866 subjects 18 years of age and older with plaque psoriasis who had a minimum body surface area involvement of 10%, a static Physician Global Assessment (sPGA) score of ≥3 in the overall assessment (plaque thickness/induration, erythema, and scaling) of psoriasis on a severity scale of 0 to 5, a Psoriasis Area and Severity Index (PASI) score ≥12, and who were candidates for phototherapy or systemic therapy.

In all three trials, subjects were randomized to either placebo or TALTZ (80 mg every 2 weeks [Q2W]) for 12 weeks, following a 160 mg starting dose. In the two active comparator trials (Trials 2 and 3), subjects were also randomized to receive U.S. approved etanercept 50 mg twice weekly for 12 weeks.

All three trials assessed the changes from baseline to Week 12 in the two co-primary endpoints: 1) PASI 75, the proportion of subjects who achieved at least a 75% reduction in the PASI composite score that takes into consideration both the percentage of body surface area affected and the nature and severity of psoriatic changes (induration, erythema and scaling) within the affected regions, and 2) sPGA of “0” (clear) or “1” (minimal), the proportion of subjects with an sPGA 0 or 1 and at least a 2-point improvement.

Other evaluated outcomes included the proportion of subjects with an sPGA score of 0 (clear), a reduction of at least 90% in PASI (PASI 90), a reduction of 100% in PASI (PASI 100), and an improvement of itch severity as measured by a reduction of at least 4 points on an 11-point itch Numeric Rating Scale.

Subjects in all treatment groups had a median baseline PASI score ranging from approximately 17 to 18. Baseline sPGA score was severe or very severe in 51% of subjects in Trial 1, 50% in Trial 2, and 48% in Trial 3.

Of all subjects, 44% had received prior phototherapy, 49% had received prior conventional systemic therapy, and 26% had received prior biologic therapy for the treatment of psoriasis. Of the subjects who had received prior biologic therapy, 15% had received at least one anti-TNF alpha agent, and 9% had received an anti-IL 12/IL23. A total of 23% of study subjects had a history of psoriatic arthritis.

The safety and efficacy of TALTZ were assessed in 567 patients, in 2 randomized, double-blind, placebo-controlled studies (AS1 and AS2) in adult patients, age 18 years and older with active ankylosing spondylitis. Patients had active disease as defined by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥4 despite non-steroidal anti-inflammatory drug (NSAID), corticosteroid, or disease modifying anti-rheumatic drug (DMARD) therapy. At baseline, patients had symptoms of AS for an average of 17 years across both studies. At baseline, approximately 32% of the patients were on a concomitant cDMARD. In AS2, all patients discontinued previous treatment with 1 or 2 TNF inhibitors due to either inadequate response or intolerance.

AS1 Study (NCT 02696785) evaluated 341 biologic-naive patients, who were treated with either TALTZ 80 mg or 160 mg at Week 0 followed by 80 mg every 2 weeks (Q2W) or 4 weeks (Q4W), adalimumab 40 mg every 2 weeks, or with placebo. Patients receiving placebo were re-randomized at Week 16 to receive TALTZ (160 mg starting dose, followed by 80 mg Q2W or Q4W). Patients receiving adalimumab were re-randomized at Week 16 to receive TALTZ (80 mg Q2W or Q4W). AS2 Study (NCT 02696798) evaluated 316 TNF-inhibitor experienced patients (90% were inadequate responders and 10% were intolerant to TNF inhibitors). All patients were treated with TALTZ 80 or 160 mg at Week 0 followed by 80 mg Q2W or Q4W, or with placebo. Patients receiving placebo were re-randomized at Week 16 to receive TALTZ (160 mg initial dose, followed by 80 mg Q2W or Q4W). The primary endpoint in both studies was the percentage of patients achieving an Assessment of Spondyloarthritis International Society 40 (ASAS40) response at Week 16.

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).

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.

TALTZ is a clear and colorless to slightly yellow solution available as:

• Injection: 80 mg/mL solution of TALTZ in a single-dose prefilled autoinjector
• Injection: 80 mg/mL solution of TALTZ in a single-dose prefilled syringe
• Injection: 40 mg/0.5 mL solution of TALTZ in a single-dose prefilled syringe
• Injection: 20 mg/0.25 mL solution of TALTZ in a single-dose prefilled syringe

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)].

Infections: bacterial, viral, and fungal opportunistic infections, including cryptococcal meningoencephalitis, esophageal and disseminated mucocutaneous candidiasis, pulmonary tuberculosis, toxoplasmosis, varicella zoster virus reactivation, cytomegalovirus colitis, pulmonary aspergillosis.

Skin and subcutaneous tissue disorders: Eczematous eruptions (erythroderma, atopic dermatitis-like eruptions, and dyshidrotic eczema).

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.

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.

A randomized, double-blind, multicenter, placebo-controlled trial (IXORA-Peds, NCT03073200) enrolled 171 pediatric subjects 6 to less than 18 years of age, with moderate-to-severe plaque psoriasis (as defined by a sPGA score ≥3, involving ≥10% of the body surface area, and a PASI score ≥12) who were candidates for phototherapy or systemic therapy or were inadequately controlled on topical therapy.

Subjects were randomized to placebo or TALTZ with dosing stratified by weight.

• <25 kg: 40 mg at Week 0 followed by 20 mg Q4W
• 25 kg to 50 kg: 80 mg at Week 0 followed by 40 mg Q4W
• >50 kg: 160 mg at Week 0 followed by 80 mg Q4W

Response to treatment was assessed at 12 weeks of therapy and was defined by the proportion of subjects who achieved an sPGA score of “0” (clear) or “1” (almost clear) with at least a 2-point improvement from baseline and the proportion of subjects that achieved a reduction in PASI score of at least 75% (PASI 75) from baseline.

Other evaluated outcomes included the proportion of subjects who achieved PASI 90, PASI 100, sPGA of “0” and an improvement of itch severity as measured by a reduction of at least 4 points on an 11-point itch Numeric Rating Scale.

Subjects had a median baseline PASI score of 17 (range 12-49). Baseline sPGA score was severe or very severe in 49%. Of all subjects, 22% had received prior phototherapy and 32% had received prior conventional systemic therapy for the treatment of psoriasis.

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, and that serious infections, including opportunistic infections, may occur with the use of TALTZ. 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 (5.1)].

Allergic Reactions: Advise patients to seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions [see Warnings and Precautions (5.3)].

Eczematous Eruptions: Inform patients that skin reactions resembling eczema may occur with the use of TALTZ. Instruct patients to seek medical advice if they develop signs or symptoms of eczema [see Warnings and Precautions (5.4)].

Pregnancy: Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to TALTZ during pregnancy. Advise patients to contact the registry at 1-800-284-1695 to enroll [see Use in Specific Populations (8.1)].

Eli Lilly and Company, Indianapolis, IN 46285, USA

US License Number 1891

Copyright © 2016, 2024, Eli Lilly and Company. All rights reserved.

TAL-0016-USPI-20240820

taltz^®

(ixekizumab)

injection

80 mg/mL

For Subcutaneous Use Only

1 Single-Dose prefilled autoinjector

Discard any unused product.

NDC 0002-1445-11

1 x 1 mL Single-Dose prefilled autoinjector

Rx Only

Dispense enclosed Medication Guide to each patient.

Lilly

TALTZ is indicated for the treatment of adult patients with active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation.

The efficacy and safety of TALTZ were assessed in a randomized, double-blind, 52-week placebo-controlled study (nr-axSpA1) (NCT 02757352) in patients ≥18 years of age with active axial spondyloarthritis for at least 3 months. Patients must have had objective signs of inflammation indicated by elevated C-reactive protein (CRP) (defined as greater than 5 mg/L), and/or sacroiliitis on magnetic resonance imaging (MRI), and no definitive radiographic evidence of structural damage on sacroiliac joints. Patients had active disease as defined by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥4, and spinal pain ≥4 on a 0 to 10 Numerical Rating Scale (NRS). Patients must have been intolerant to or had an inadequate response to at least two NSAIDs. Patients were treated with either placebo or TALTZ 80 mg or 160 mg at Week 0, followed by either 80 mg every 2 weeks (Q2W) or 80 mg every 4 weeks (Q4W). Initiation and/or dose adjustment of concomitant medications (NSAIDs, cDMARDs, corticosteroids, analgesics) were permitted starting at Week 16. Patients were allowed to transition to use of open-label TALTZ 80 mg Q2W starting at Week 16 up to Week 44 at the discretion of the investigator.

At baseline, patients had symptoms of nr-axSpA for an average of 11 years. Approximately 39% of the patients were on a concomitant cDMARD.

The primary endpoint was the percentage of patients achieving an Assessment of Spondyloarthritis International Society 40 (ASAS40) response at Week 52. The ASAS40 response was also evaluated at Week 16 as a major secondary endpoint.

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).

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.

TALTZ is intended for use under the guidance and supervision of a healthcare provider. Adult patients may self-inject or caregivers may give injections of TALTZ after training in subcutaneous injection technique using the autoinjector or prefilled syringe. Safety and effectiveness of pediatric self-administration has not been established. Therefore, TALTZ should be administered to pediatric patients by a healthcare provider or by a caregiver who has received training and demonstrated proper subcutaneous injection technique.

TALTZ 20 mg and 40 mg doses prepared from the TALTZ 80 mg/mL prefilled syringe should only be administered by a qualified healthcare professional [see Dosage and Administration (2.8)].

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.

TALTZ is administered by subcutaneous injection. The recommended dosage in adults with moderate-to-severe plaque psoriasis 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.

The recommended dosage is 160 mg by subcutaneous injection (two 80 mg injections) at Week 0, followed by 80 mg every 4 weeks.

taltz^®

(ixekizumab)

injection

20 mg/0.25 mL

For Subcutaneous Use Only

1 Single-Dose prefilled syringe

Discard any unused product.

NDC 0002-8900-11

1 x 0.25 mL Single-Dose prefilled syringe

Rx Only

Dispense enclosed Medication Guide to each patient.

Lilly

taltz^®

(ixekizumab)

injection

40 mg/0.5 mL

For Subcutaneous Use Only

1 Single-Dose prefilled syringe

Discard any unused product.

NDC 0002-8905-11

1 x 0.5 mL Single-Dose prefilled syringe

Rx Only

Dispense enclosed Medication Guide to each patient.

Lilly

taltz^®

(ixekizumab)

injection

80 mg/mL

For Subcutaneous Use Only

1 Single-Dose prefilled syringe

Discard any unused product.

NDC 0002-7724-11

1 x 1 mL Single-Dose prefilled syringe

Rx Only

Dispense enclosed Medication Guide to each patient.

Lilly

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.

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 (5.6)].

Animal studies have not been conducted to evaluate the carcinogenic or mutagenic potential of TALTZ. Moreover published literature is mixed on potential effects on malignancy risk due to the inhibition of IL-17A activity, the pharmacological action of TALTZ. Some published literature suggests that IL-17A directly promotes cancer cell invasion, suggesting a potential beneficial effect by TALTZ, whereas other reports indicate IL-17A promotes T-cell mediated tumor rejection, suggesting a potential adverse effect by TALTZ. However, neutralization of IL-17A with TALTZ has not been studied in these models. Depletion of IL-17A with a neutralizing antibody inhibited tumor development in mice, suggesting a potential beneficial effect by TALTZ. The relevance of experimental findings in mouse models for malignancy risk in humans is unknown.

No effects on fertility parameters such as reproductive organs, menstrual cycle length, or sperm analysis were observed in sexually mature cynomolgus monkeys that were administered ixekizumab for 13 weeks at a subcutaneous dose of 50 mg/kg/week (19 times the MRHD on a mg/kg basis). The monkeys were not mated to evaluate fertility.

The recommended dosage is 80 mg by subcutaneous injection every 4 weeks.

How Supplied

TALTZ injection is a sterile, preservative free, clear and colorless to slightly yellow solution available in:

• a single-dose prefilled autoinjector or a single-dose prefilled syringe to deliver 80 mg ixekizumab.
• a single-dose prefilled syringe to deliver 40 mg ixekizumab.
• a single-dose prefilled syringe to deliver 20 mg ixekizumab.

TALTZ is supplied as:

If the 20 mg/0.25 mL or 40 mg/0.5 mL prefilled syringe is unavailable, TALTZ doses of 20 mg or 40 mg for pediatric patients with plaque psoriasis [see Dosage and Administration (2.3)] must be manually prepared according to the steps below using only the TALTZ 80 mg/mL prefilled syringe. The preparation and administration of the 20 mg and 40 mg doses should only be performed by a qualified healthcare professional. For additional preparation and administration instructions, [see Dosage and Administration (2.7)].

• 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.
• Expel the entire contents of the prefilled syringe into the sterile vial. DO NOT shake or swirl the vial. Do not add other medications to solutions containing TALTZ.
• 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).
• Remove the needle from the syringe and replace it with a 27-gauge needle prior to administering TALTZ.

Storage of Prepared TALTZ

If necessary, TALTZ 20 mg or 40 mg doses prepared from an 80 mg/mL prefilled syringe may be stored at room temperature for up to 4 hours from first puncturing the sterile vial.

Storage and Handling

TALTZ is sterile and preservative-free. Discard any unused portion.

• TALTZ must be protected from light until use.
• Store refrigerated at 2°C to 8°C (36°F to 46°F).
  • If needed, patients/caregivers may store TALTZ at room temperature up to 30°C (86°F) for up to 5 days in the original carton to protect from light. Once TALTZ has been stored at room temperature, do not return to the refrigerator and discard, if unused, within 5 days.
  • Record the date when TALTZ is first removed from the refrigerator in the spaces provided on the carton.
  • For the 2 or 3 autoinjector pack, remove a single autoinjector at a time leaving the remaining autoinjector(s) in the original carton in the refrigerator. Ensure the unrefrigerated TALTZ is protected from light.
• Do not freeze. Do not use TALTZ if it has been frozen.
• Do not shake.
• Discard the TALTZ single-dose autoinjector or syringe after use in a puncture-resistant container.
• Not made with natural rubber latex.

Risk Summary

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.

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 standard technology for bioprocessing. Ixekizumab is comprised of two identical light chain polypeptides of 219 amino acids each and two identical heavy chain polypeptides of 445 amino acids each and has a molecular weight of 146,158 Daltons for the protein backbone of the molecule.

TALTZ injection is a sterile, preservative free, clear and colorless to slightly yellow solution, for subcutaneous use available as 80 mg of ixekizumab in a 1 mL single-dose prefilled autoinjector or a single-dose prefilled syringe, 40 mg of ixekizumab in a 0.5 mL single-dose prefilled syringe, or 20 mg of ixekizumab in a 0.25 mL single-dose prefilled syringe. The prefilled autoinjector and prefilled syringe each contain a 1 mL glass syringe with a fixed 27 gauge ½ inch needle. The TALTZ 80 mg prefilled autoinjector and prefilled syringe are manufactured to deliver 80 mg of ixekizumab. The TALTZ 40 mg prefilled syringe is manufactured to deliver 40 mg of ixekizumab. The TALTZ 20 mg prefilled syringe is manufactured to deliver 20 mg of ixekizumab.

Each TALTZ 80 mg/mL single-dose autoinjector or TALTZ 80 mg/mL single-dose prefilled syringe is composed of ixekizumab (80 mg); Polysorbate 80, USP (0.3 mg); Sucrose, USP (80 mg); and Water for Injection, USP. Sodium Hydroxide, USP-NF, may have been added to adjust pH. The TALTZ solution has a pH of 5.2 –  6.2.

Each TALTZ 40 mg/0.5 mL single-dose prefilled syringe is composed of ixekizumab (40 mg); Polysorbate 80, USP (0.15 mg); Sucrose, USP (40 mg); and Water for Injection, USP. Sodium Hydroxide, USP-NF, may have been added to adjust pH. The TALTZ solution has a pH of 5.2 –  6.2.

Each TALTZ 20 mg/0.25 mL single-dose prefilled syringe is composed of ixekizumab (20 mg); Polysorbate 80, USP (0.08 mg); Sucrose, USP (20 mg); and Water for Injection, USP. Sodium Hydroxide, USP-NF, may have been added to adjust pH. The TALTZ solution has a pH of 5.2 –  6.2.

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)].

In the postmarketing setting, serious bacterial, viral, and fungal opportunistic infections have been reported in patients receiving IL-17 inhibitors including TALTZ. 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.

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.

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.

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)].

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.

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)].

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)]
• Eczematous Eruptions [see Warnings and Precautions (5.4)]
• Inflammatory Bowel Disease [see Warnings and Precautions (5.5)]

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.

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.

No formal pharmacodynamic studies have been conducted with TALTZ.

The pharmacokinetic (PK) properties of ixekizumab were similar across the adult plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, and non-radiographic axial spondyloarthritis indications.

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)

TALTZ is indicated for the treatment of adult patients with active psoriatic arthritis.

Ixekizumab is a humanized IgG4 monoclonal antibody that selectively binds with the interleukin 17A (IL-17A) cytokine and inhibits its interaction with the IL-17 receptor. IL-17A is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Ixekizumab inhibits the release of proinflammatory cytokines and chemokines.

The safety and efficacy of TALTZ were assessed in 679 patients, in 2 randomized, double-blind, placebo-controlled studies (PsA1 and PsA2) in adult patients, age 18 years and older with active psoriatic arthritis (at least 3 swollen and at least 3 tender joints) despite non-steroidal anti-inflammatory drug (NSAID), corticosteroid or disease modifying anti-rheumatic drug (DMARD) therapy. Patients in these studies had a diagnosis of PsA for at least 6 months across both studies. At baseline, 60% and 23% of the patients had enthesitis and dactylitis, respectively. In PsA2, all patients discontinued previous treatment with anti-TNFα agents due to either inadequate response or intolerance. In addition, approximately 47% of patients from both studies had concomitant methotrexate (MTX) use.

PsA1 Study (NCT 01695239) evaluated 417 biologic-naive patients, who were treated with either TALTZ 160 mg at Week 0 followed by 80 mg every 2 weeks (Q2W) or 4 weeks (Q4W), adalimumab 40 mg every 2 weeks, or placebo. PsA2 Study (NCT 02349295) evaluated 363 anti-TNFα experienced patients, who were treated with TALTZ 160 mg at Week 0 followed by 80 mg every 2 or 4 weeks, or placebo. Patients receiving placebo were re-randomized to receive TALTZ (80 mg every 2 or 4 weeks) at Week 16 or Week 24 based on responder status. The primary endpoint was the percentage of patients achieving an ACR20 response at Week 24.

TALTZ is indicated for the treatment of adult patients with active ankylosing spondylitis.

• 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)
• Eczematous Eruptions: In the postmarketing setting, cases of severe eczematous eruptions were reported in patients receiving TALTZ. Treatment may need to be discontinued to resolve the eczematous eruption. (5.4)
• 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. (5.5)
• Immunizations: Avoid use of live vaccines. (5.6)

Three multicenter, randomized, double-blind, placebo-controlled trials, Trials 1, 2, and 3 (NCT 01474512, NCT 01597245, NCT 01646177), enrolled a total of 3866 subjects 18 years of age and older with plaque psoriasis who had a minimum body surface area involvement of 10%, a static Physician Global Assessment (sPGA) score of ≥3 in the overall assessment (plaque thickness/induration, erythema, and scaling) of psoriasis on a severity scale of 0 to 5, a Psoriasis Area and Severity Index (PASI) score ≥12, and who were candidates for phototherapy or systemic therapy.

In all three trials, subjects were randomized to either placebo or TALTZ (80 mg every 2 weeks [Q2W]) for 12 weeks, following a 160 mg starting dose. In the two active comparator trials (Trials 2 and 3), subjects were also randomized to receive U.S. approved etanercept 50 mg twice weekly for 12 weeks.

All three trials assessed the changes from baseline to Week 12 in the two co-primary endpoints: 1) PASI 75, the proportion of subjects who achieved at least a 75% reduction in the PASI composite score that takes into consideration both the percentage of body surface area affected and the nature and severity of psoriatic changes (induration, erythema and scaling) within the affected regions, and 2) sPGA of “0” (clear) or “1” (minimal), the proportion of subjects with an sPGA 0 or 1 and at least a 2-point improvement.

Other evaluated outcomes included the proportion of subjects with an sPGA score of 0 (clear), a reduction of at least 90% in PASI (PASI 90), a reduction of 100% in PASI (PASI 100), and an improvement of itch severity as measured by a reduction of at least 4 points on an 11-point itch Numeric Rating Scale.

Subjects in all treatment groups had a median baseline PASI score ranging from approximately 17 to 18. Baseline sPGA score was severe or very severe in 51% of subjects in Trial 1, 50% in Trial 2, and 48% in Trial 3.

Of all subjects, 44% had received prior phototherapy, 49% had received prior conventional systemic therapy, and 26% had received prior biologic therapy for the treatment of psoriasis. Of the subjects who had received prior biologic therapy, 15% had received at least one anti-TNF alpha agent, and 9% had received an anti-IL 12/IL23. A total of 23% of study subjects had a history of psoriatic arthritis.

The safety and efficacy of TALTZ were assessed in 567 patients, in 2 randomized, double-blind, placebo-controlled studies (AS1 and AS2) in adult patients, age 18 years and older with active ankylosing spondylitis. Patients had active disease as defined by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥4 despite non-steroidal anti-inflammatory drug (NSAID), corticosteroid, or disease modifying anti-rheumatic drug (DMARD) therapy. At baseline, patients had symptoms of AS for an average of 17 years across both studies. At baseline, approximately 32% of the patients were on a concomitant cDMARD. In AS2, all patients discontinued previous treatment with 1 or 2 TNF inhibitors due to either inadequate response or intolerance.

AS1 Study (NCT 02696785) evaluated 341 biologic-naive patients, who were treated with either TALTZ 80 mg or 160 mg at Week 0 followed by 80 mg every 2 weeks (Q2W) or 4 weeks (Q4W), adalimumab 40 mg every 2 weeks, or with placebo. Patients receiving placebo were re-randomized at Week 16 to receive TALTZ (160 mg starting dose, followed by 80 mg Q2W or Q4W). Patients receiving adalimumab were re-randomized at Week 16 to receive TALTZ (80 mg Q2W or Q4W). AS2 Study (NCT 02696798) evaluated 316 TNF-inhibitor experienced patients (90% were inadequate responders and 10% were intolerant to TNF inhibitors). All patients were treated with TALTZ 80 or 160 mg at Week 0 followed by 80 mg Q2W or Q4W, or with placebo. Patients receiving placebo were re-randomized at Week 16 to receive TALTZ (160 mg initial dose, followed by 80 mg Q2W or Q4W). The primary endpoint in both studies was the percentage of patients achieving an Assessment of Spondyloarthritis International Society 40 (ASAS40) response at Week 16.

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).

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.

TALTZ is a clear and colorless to slightly yellow solution available as:

• Injection: 80 mg/mL solution of TALTZ in a single-dose prefilled autoinjector
• Injection: 80 mg/mL solution of TALTZ in a single-dose prefilled syringe
• Injection: 40 mg/0.5 mL solution of TALTZ in a single-dose prefilled syringe
• Injection: 20 mg/0.25 mL solution of TALTZ in a single-dose prefilled syringe

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)].

Infections: bacterial, viral, and fungal opportunistic infections, including cryptococcal meningoencephalitis, esophageal and disseminated mucocutaneous candidiasis, pulmonary tuberculosis, toxoplasmosis, varicella zoster virus reactivation, cytomegalovirus colitis, pulmonary aspergillosis.

Skin and subcutaneous tissue disorders: Eczematous eruptions (erythroderma, atopic dermatitis-like eruptions, and dyshidrotic eczema).

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.

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.

A randomized, double-blind, multicenter, placebo-controlled trial (IXORA-Peds, NCT03073200) enrolled 171 pediatric subjects 6 to less than 18 years of age, with moderate-to-severe plaque psoriasis (as defined by a sPGA score ≥3, involving ≥10% of the body surface area, and a PASI score ≥12) who were candidates for phototherapy or systemic therapy or were inadequately controlled on topical therapy.

Subjects were randomized to placebo or TALTZ with dosing stratified by weight.

• <25 kg: 40 mg at Week 0 followed by 20 mg Q4W
• 25 kg to 50 kg: 80 mg at Week 0 followed by 40 mg Q4W
• >50 kg: 160 mg at Week 0 followed by 80 mg Q4W

Response to treatment was assessed at 12 weeks of therapy and was defined by the proportion of subjects who achieved an sPGA score of “0” (clear) or “1” (almost clear) with at least a 2-point improvement from baseline and the proportion of subjects that achieved a reduction in PASI score of at least 75% (PASI 75) from baseline.

Other evaluated outcomes included the proportion of subjects who achieved PASI 90, PASI 100, sPGA of “0” and an improvement of itch severity as measured by a reduction of at least 4 points on an 11-point itch Numeric Rating Scale.

Subjects had a median baseline PASI score of 17 (range 12-49). Baseline sPGA score was severe or very severe in 49%. Of all subjects, 22% had received prior phototherapy and 32% had received prior conventional systemic therapy for the treatment of psoriasis.

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, and that serious infections, including opportunistic infections, may occur with the use of TALTZ. 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 (5.1)].

Allergic Reactions: Advise patients to seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions [see Warnings and Precautions (5.3)].

Eczematous Eruptions: Inform patients that skin reactions resembling eczema may occur with the use of TALTZ. Instruct patients to seek medical advice if they develop signs or symptoms of eczema [see Warnings and Precautions (5.4)].

Pregnancy: Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to TALTZ during pregnancy. Advise patients to contact the registry at 1-800-284-1695 to enroll [see Use in Specific Populations (8.1)].

Eli Lilly and Company, Indianapolis, IN 46285, USA

US License Number 1891

Copyright © 2016, 2024, Eli Lilly and Company. All rights reserved.

TAL-0016-USPI-20240820

taltz^®

(ixekizumab)

injection

80 mg/mL

For Subcutaneous Use Only

1 Single-Dose prefilled autoinjector

Discard any unused product.

NDC 0002-1445-11

1 x 1 mL Single-Dose prefilled autoinjector

Rx Only

Dispense enclosed Medication Guide to each patient.

Lilly

TALTZ is indicated for the treatment of adult patients with active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation.

The efficacy and safety of TALTZ were assessed in a randomized, double-blind, 52-week placebo-controlled study (nr-axSpA1) (NCT 02757352) in patients ≥18 years of age with active axial spondyloarthritis for at least 3 months. Patients must have had objective signs of inflammation indicated by elevated C-reactive protein (CRP) (defined as greater than 5 mg/L), and/or sacroiliitis on magnetic resonance imaging (MRI), and no definitive radiographic evidence of structural damage on sacroiliac joints. Patients had active disease as defined by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥4, and spinal pain ≥4 on a 0 to 10 Numerical Rating Scale (NRS). Patients must have been intolerant to or had an inadequate response to at least two NSAIDs. Patients were treated with either placebo or TALTZ 80 mg or 160 mg at Week 0, followed by either 80 mg every 2 weeks (Q2W) or 80 mg every 4 weeks (Q4W). Initiation and/or dose adjustment of concomitant medications (NSAIDs, cDMARDs, corticosteroids, analgesics) were permitted starting at Week 16. Patients were allowed to transition to use of open-label TALTZ 80 mg Q2W starting at Week 16 up to Week 44 at the discretion of the investigator.

At baseline, patients had symptoms of nr-axSpA for an average of 11 years. Approximately 39% of the patients were on a concomitant cDMARD.

The primary endpoint was the percentage of patients achieving an Assessment of Spondyloarthritis International Society 40 (ASAS40) response at Week 52. The ASAS40 response was also evaluated at Week 16 as a major secondary endpoint.

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).

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.

TALTZ is intended for use under the guidance and supervision of a healthcare provider. Adult patients may self-inject or caregivers may give injections of TALTZ after training in subcutaneous injection technique using the autoinjector or prefilled syringe. Safety and effectiveness of pediatric self-administration has not been established. Therefore, TALTZ should be administered to pediatric patients by a healthcare provider or by a caregiver who has received training and demonstrated proper subcutaneous injection technique.

TALTZ 20 mg and 40 mg doses prepared from the TALTZ 80 mg/mL prefilled syringe should only be administered by a qualified healthcare professional [see Dosage and Administration (2.8)].

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.

TALTZ is administered by subcutaneous injection. The recommended dosage in adults with moderate-to-severe plaque psoriasis 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.

The recommended dosage is 160 mg by subcutaneous injection (two 80 mg injections) at Week 0, followed by 80 mg every 4 weeks.

taltz^®

(ixekizumab)

injection

20 mg/0.25 mL

For Subcutaneous Use Only

1 Single-Dose prefilled syringe

Discard any unused product.

NDC 0002-8900-11

1 x 0.25 mL Single-Dose prefilled syringe

Rx Only

Dispense enclosed Medication Guide to each patient.

Lilly

taltz^®

(ixekizumab)

injection

40 mg/0.5 mL

For Subcutaneous Use Only

1 Single-Dose prefilled syringe

Discard any unused product.

NDC 0002-8905-11

1 x 0.5 mL Single-Dose prefilled syringe

Rx Only

Dispense enclosed Medication Guide to each patient.

Lilly

taltz^®

(ixekizumab)

injection

80 mg/mL

For Subcutaneous Use Only

1 Single-Dose prefilled syringe

Discard any unused product.

NDC 0002-7724-11

1 x 1 mL Single-Dose prefilled syringe

Rx Only

Dispense enclosed Medication Guide to each patient.

Lilly

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.

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 (5.6)].

Animal studies have not been conducted to evaluate the carcinogenic or mutagenic potential of TALTZ. Moreover published literature is mixed on potential effects on malignancy risk due to the inhibition of IL-17A activity, the pharmacological action of TALTZ. Some published literature suggests that IL-17A directly promotes cancer cell invasion, suggesting a potential beneficial effect by TALTZ, whereas other reports indicate IL-17A promotes T-cell mediated tumor rejection, suggesting a potential adverse effect by TALTZ. However, neutralization of IL-17A with TALTZ has not been studied in these models. Depletion of IL-17A with a neutralizing antibody inhibited tumor development in mice, suggesting a potential beneficial effect by TALTZ. The relevance of experimental findings in mouse models for malignancy risk in humans is unknown.

No effects on fertility parameters such as reproductive organs, menstrual cycle length, or sperm analysis were observed in sexually mature cynomolgus monkeys that were administered ixekizumab for 13 weeks at a subcutaneous dose of 50 mg/kg/week (19 times the MRHD on a mg/kg basis). The monkeys were not mated to evaluate fertility.

The recommended dosage is 80 mg by subcutaneous injection every 4 weeks.