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TALTZ- ixekizumab injection, solution 
Eli Lilly and Company


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-HIGHLIGHTS OF PRESCRIBING INFORMATION


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

Indications and Usage:      Non-radiographic Axial Spondyloarthritis (1.4)
05/2020 Dosage and Administration:      Non-radiographic Axial Spondyloarthritis
(2.5) 05/2020 Warnings and Precautions:      Infections (5.1) 05/2020




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 (2.1)

 * Recommended dose 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 (2.2)

 * For patients weighing greater than 50 kg, recommended dose is 160 mg (two
   80 mg injections) at Week 0, followed by 80 mg every 4 weeks.
 * For patients weighing 25-50 kg, recommended dose is 80 mg at Week 0, followed
   by 40 mg every 4 weeks.
 * For patients weighing less than 25 kg, recommended dose is 40 mg at Week 0,
   followed by 20 mg every 4 weeks.

Psoriatic Arthritis (2.3)

 * Recommended dose 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. (2.1)
 * TALTZ may be administered alone or in combination with a conventional DMARD
   (e.g., methotrexate).

Ankylosing Spondylitis (2.4)

 * Recommended dose is 160 mg by subcutaneous injection (two 80 mg injections)
   at Week 0, followed by 80 mg every 4 weeks.

Non-radiographic Axial Spondyloarthritis (2.5)

 * Recommended dose 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)








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 Medication Guide.

Revised: 3/2021

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+FULL PRESCRIBING INFORMATION: CONTENTS*


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 ADULT PLAQUE PSORIASIS


2.2 PEDIATRIC PLAQUE PSORIASIS


2.3 PSORIATIC ARTHRITIS


2.4 ANKYLOSING SPONDYLITIS


2.5 NON-RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS


2.6 TUBERCULOSIS ASSESSMENT PRIOR TO INITIATION OF TALTZ


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


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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+1 INDICATIONS AND USAGE


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.


1.3 ANKYLOSING SPONDYLITIS

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


1.4 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.

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+2 DOSAGE AND ADMINISTRATION


2 DOSAGE AND ADMINISTRATION


2.1 ADULT PLAQUE PSORIASIS

TALTZ is administered by subcutaneous injection. The recommended dose 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.


2.2 PEDIATRIC PLAQUE PSORIASIS

TALTZ is administered by subcutaneous injection every 4 weeks (Q4W). The
recommended dose 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.

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


2.3 PSORIATIC ARTHRITIS

The recommended dose 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 (2.1)].

TALTZ may be administered alone or in combination with a conventional
disease-modifying antirheumatic drug (cDMARD) (e.g., methotrexate).


2.4 ANKYLOSING SPONDYLITIS

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


2.5 NON-RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS

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


2.6 TUBERCULOSIS ASSESSMENT PRIOR TO INITIATION OF TALTZ

Evaluate patients for tuberculosis (TB) infection prior to initiating treatment
with TALTZ [see Warnings and Precautions (5.2)].


2.7 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.

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 (2.2)] 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.

 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.

Storage

If necessary, the prepared TALTZ may be stored at room temperature for up to 4
hours from first puncturing the sterile vial.

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+3 DOSAGE FORMS AND STRENGTHS


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

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+4 CONTRAINDICATIONS


4 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)].

Hide


+5 WARNINGS AND PRECAUTIONS


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

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.

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+6 ADVERSE REACTIONS


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)]


6.1 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

a Upper respiratory tract infections cluster includes nasopharyngitis and
rhinovirus infection.

b U.S. approved etanercept.

Adverse Reactions TALTZ 80 mg Q2W
(N=1167) n (%) Etanerceptb
(N=287) n (%) Placebo
(N=791) n (%) Injection site reactions 196 (17) 32 (11) 26 (3) Upper respiratory
tract infectionsa 163 (14) 23 (8) 101 (13) Nausea 23 (2) 1 (<1) 5 (1) Tinea
infections 17 (2) 0 1 (<1)

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 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

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)].

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+8 USE IN SPECIFIC POPULATIONS


8 USE IN SPECIFIC POPULATIONS


8.1 PREGNANCY

Risk Summary

There are no available data on TALTZ use in pregnant women to inform any drug
associated risks. 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 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. 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 infants
from birth through 6 months of age.


8.2 LACTATION

Risk Summary

There are no 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. 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)].

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+11 DESCRIPTION


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 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. 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.

Each mL is composed of ixekizumab (80 mg); Citric Acid Anhydrous, USP (0.51 mg);
Polysorbate 80, USP (0.3 mg); Sodium Chloride, USP (11.69 mg); Sodium Citrate
Dihydrate, USP (5.11 mg); and Water for Injection, USP. The TALTZ solution has a
pH of 5.3 – 6.1.

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+12 CLINICAL PHARMACOLOGY


12 CLINICAL PHARMACOLOGY


12.1 MECHANISM OF ACTION

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.


12.2 PHARMACODYNAMICS

No formal pharmacodynamic studies have been conducted with TALTZ.


12.3 PHARMACOKINETICS

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

Absorption

Following a single subcutaneous dose of 160 mg in subjects with plaque
psoriasis, ixekizumab reached peak mean (±SD) serum concentrations (Cmax) of
16.2 ±6.6 mcg/mL by approximately 4 days post dose.

Steady-state concentrations were achieved by Week 8 following the 160 mg
starting dose and 80 mg every 2 weeks dosing regimen; the mean ±SD steady-state
trough concentration was 9.3 ±5.3 mcg/mL. Steady-state concentrations were
achieved approximately 10 weeks after switching from the 80 mg every 2 weeks
dosing regimen to the 80 mg every 4 weeks dosing regimen at Week 12. The mean
±SD steady-state trough concentration was 3.5 ±2.5 mcg/mL.

In studies of subjects with plaque psoriasis, ixekizumab bioavailability ranged
from 60% to 81% following subcutaneous injection. Administration of ixekizumab
via injection in the thigh achieved a higher bioavailability relative to that
achieved using other injection sites including the arm and abdomen.

Distribution

The mean (geometric CV%) volume of distribution at steady-state was 7.11 L (29%)
in subjects with plaque psoriasis.

Elimination

The metabolic pathway of ixekizumab has not been characterized. As a humanized
IgG4 monoclonal antibody ixekizumab is expected to be degraded into small
peptides and amino acids via catabolic pathways in the same manner as endogenous
IgG.

The mean systemic clearance was 0.39 L/day (37%) and the mean (geometric CV%)
half-life was 13 days (40%) in subjects with plaque psoriasis.

Weight

Ixekizumab clearance and volume of distribution increase as body weight
increases.

Dose Linearity

Ixekizumab exhibited dose-proportional pharmacokinetics in subjects with plaque
psoriasis over a dose range from 5 mg (not the recommended dose) to 160 mg
following subcutaneous administration.

Specific Populations

Age:

Geriatric Population

Population pharmacokinetic analysis indicated that age did not significantly
influence the clearance of ixekizumab in adult subjects with plaque psoriasis.
Subjects who are 65 years or older had a similar ixekizumab clearance as
compared to subjects less than 65 years old.

Pediatric Population

Pediatric psoriasis subjects (6 to less than 18 years of age) were administered
ixekizumab at the recommended pediatric dosing regimen for 12 weeks. Subjects
weighing >50 kg and 25 to 50 kg had a mean ±SD steady-state trough concentration
of 3.8 ±2.2 mcg/mL and 3.9 ±2.4 mcg/mL at Week 12, respectively. There were
limited PK data (n=2) in subjects weighing <25 kg at Week 12.

Drug Interaction Studies

Population PK data analyses indicated that the clearance of ixekizumab was not
impacted by concomitant administration of methotrexate, or by prior exposure to
methotrexate or adalimumab in patients with psoriatic arthritis.

Population PK data analyses indicated that the clearance of ixekizumab was not
impacted by concomitant administration of oral corticosteroids, NSAIDs, or
cDMARDs (sulfasalazine and methotrexate) in patients with ankylosing spondylitis
and non-radiographic axial spondyloarthritis.

Cytochrome P450 Substrates

No clinically significant changes in exposure of caffeine (CYP1A2 substrate),
warfarin (CYP2C9 substrate), omeprazole (CYP2C19 substrate) or midazolam (CYP3A
substrate) were observed in subjects with plaque psoriasis when used
concomitantly with a single 160 mg dose of ixekizumab, or multiple doses of 80
mg every 2 weeks. The potential effect of ixekizumab on the CYP2D6 activity
cannot be ruled out due to high variability in exposure (approximately ±2-fold)
of dextromethorphan and its CYP2D6 metabolite dextrorphan in psoriasis subjects.

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+13 NONCLINICAL TOXICOLOGY


13 NONCLINICAL TOXICOLOGY


13.1 CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY

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.

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+14 CLINICAL STUDIES


14 CLINICAL STUDIES


14.1 ADULT PLAQUE PSORIASIS

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.

Clinical Response at Week 12

The results of Trials 1, 2, and 3 are presented in Table 3.

Table 3: Efficacy Results at Week 12 in Adults with Plaque Psoriasis in Trials
1, 2, and 3; NRIa

a Abbreviations: N = number of patients in the intent-to-treat population; NRI =
Non-Responder Imputation.

b At Week 0, subjects received 160 mg of TALTZ.

c Co-primary endpoints.

d Itch NRS (≥4 improvement) in subjects with baseline Itch NRS ≥4. The number of
ITT subjects with baseline Itch NRS Score ≥4 are as follows: Trial 1, TALTZ
n=391, PBO n=374; Trial 2, TALTZ n=303, PBO n=135; Trial 3, TALTZ n=320, PBO
n=158.

Trial 1 Trial 2 Trial 3 TALTZ 80 mgb
Q2W (N=433)
n (%) Placebo
(N=431)
n (%) TALTZ 80 mgb
Q2W (N=351)
n (%) Placebo
(N=168)
n (%) TALTZ 80 mgb
Q2W (N=385)
n (%) Placebo
(N=193)
n (%) sPGA of “0” (clear) or “1” (minimal)c 354 (82) 14 (3) 292 (83) 4 (2) 310
(81) 13 (7) sPGA of “0” (clear) 160 (37) 0 147 (42) 1 (1) 155 (40) 0 PASI 75c
386 (89) 17 (4) 315 (90) 4 (2) 336 (87) 14 (7) PASI 90 307 (71) 2 (1) 248 (71) 1
(1) 262 (68) 6 (3) PASI 100 153 (35) 0 142 (40) 1 (1) 145 (38) 0 Itch NRS (≥4
point improvement)d 336 (86) 58 (16) 258 (85) 19 (14) 264 (83) 33 (21)

Examination of age, gender, race, body weight, and previous treatment with a
biologic did not identify differences in response to TALTZ among these subgroups
at Week 12.

An integrated analysis of the U.S. sites in the two active comparator studies
using U.S. approved etanercept, TALTZ demonstrated superiority to U.S. approved
etanercept (50 mg twice weekly) on sPGA and PASI scores during the 12 week
treatment period. The respective response rates for TALTZ 80 mg Q2W and U.S.
approved etanercept 50 mg twice weekly were: sPGA of 0 or 1 (73% and 27%); PASI
75 (87% and 41%); sPGA of 0 (34% and 5%); PASI 90 (64% and 18%), and PASI 100
(34% and 4%).

Maintenance and Durability of Response

To evaluate the maintenance and durability of response, subjects originally
randomized to TALTZ and who were responders at Week 12 (i.e., sPGA of 0 or 1) in
Trial 1 and Trial 2 were re-randomized to an additional 48 weeks of either a
maintenance dose of TALTZ 80 mg Q4W (every 4 weeks) or placebo. Non-responders
(sPGA >1) at Week 12 and subjects who relapsed (sPGA ≥3) during the maintenance
period were placed on TALTZ 80 mg Q4W.

For responders at Week 12, the percentage of subjects who maintained this
response (sPGA 0 or 1) at Week 60 (48 weeks following re-randomization) in the
integrated trials (Trial 1 and Trial 2) was higher for subjects treated with
TALTZ 80 mg Q4W (75%) compared to those treated with placebo (7%).

For responders at Week 12 who were re-randomized to treatment withdrawal (i.e.,
placebo), the median time to relapse (sPGA ≥3) was 164 days in the integrated
trials. Among these subjects, 66% regained a response of at least 0 or 1 on the
sPGA within 12 weeks of restarting treatment with TALTZ 80 mg Q4W.

Psoriasis Involving the Genital Area

A randomized, double-blind, placebo-controlled trial (Trial 4) was conducted in
149 adult subjects with plaque psoriasis who had a minimum body surface area
(BSA) involvement of 1%, a sPGA score of ≥3 (moderate psoriasis), a sPGA of
Genitalia score of ≥3 (moderate psoriasis involving the genital area), who
failed to respond to or were intolerant of at least one topical therapy used for
treatment of psoriasis affecting the genital area, and who were candidates for
phototherapy and/or systemic therapy.

Subjects had a median baseline PASI score of approximately 12. Baseline BSA
involvement was at least 10% for approximately 60% of the enrolled subjects.
Baseline sPGA of Genitalia score was severe or very severe in approximately 42%
of the subjects; baseline sPGA score was severe or very severe in approximately
47% of the subjects.

Subjects randomized to TALTZ received an initial dose of 160 mg followed by
80 mg every 2 weeks for 12 weeks. The trial evaluated the primary endpoint of
the proportion of subjects who achieved a “0” (clear) or “1” (minimal) response
at Week 12 on sPGA of Genitalia. Other evaluated outcomes at Week 12 included
the proportion of subjects who achieved a sPGA score of “0” (clear) or “1”
(minimal), improvement of genital itch severity as measured by a reduction of at
least 4 points in the 11-point Genital Psoriasis Symptoms Scale (GPSS) score
Itch numeric rating scale (NRS), and the patient-perceived impact of psoriasis
affecting the genital area on limiting frequency of sexual activity (intercourse
or other activities) as measured by the Genital Psoriasis Sexual Frequency
Questionnaire (GenPs-SFQ) Item 2 (In the past week how often did your genital
psoriasis limit the frequency of your sexual activity?). SFQ Item 2 score ranges
from 0 to 4 (0=never, 1=rarely, 2=sometimes, 3=often, 4=always); where higher
scores indicate greater limitations on the frequency of sexual activity in the
past week.

The results of Trial 4 are presented in Table 4.

Table 4: Efficacy Results at Week 12 in Adults with Genital Psoriasis in Trial
4; NRIa

a Abbreviations: NRI = Non-Responder Imputation; GPSS = Genital Psoriasis
Symptoms Scale; GenPs-SFQ = Genital Psoriasis Sexual Frequency Questionnaire.

b At Week 0, subjects received 160 mg of TALTZ, followed by 80 mg every 2 weeks
for 12 weeks.

Endpoints TALTZ 80 mg Q2Wb
n (%) Placebo
n (%) Number of subjects randomized N=75 N=74        sPGA of Genitalia “0”
(clear) or “1” (minimal) 55 (73%) 6 (8%)        sPGA “0” (clear) or “1”
(minimal) 55 (73%) 2 (3%) Number of subjects with baseline GPSSa Itch NRS Score
≥4 N=56 N=51        GPSS Genital Itch (≥4 point improvement) 31 (55%) 3 (6%)
Number of subjects with baseline GenPs-SFQa Item 2 Score ≥2 N=37 N=42      
 GenPs-SFQ Item 2 score “0” (never) or “1” (rarely) 29 (78%) 9 (21%)


14.2 PEDIATRIC PLAQUE PSORIASIS

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.

Clinical Response

The efficacy results of IXORA-Peds are presented in Table 5.

Table 5: Efficacy Results in Pediatric Subjects with Plaque Psoriasis in
IXORA-Peds, NRIa

a Abbreviations: N = Number of subjects in the intent-to-treat population; NRI =
Non-Responder Imputation.

b At Week 0, subjects received 160 mg, 80 mg, or 40 mg of TALTZ, followed by
80 mg, 40 mg, or 20 mg every 4 weeks, depending on weight category, for 12
weeks.

c Co-primary endpoints.

d Itch NRS (≥4 improvement) in subjects with baseline Itch NRS ≥4. The number of
ITT subjects with baseline Itch NRS Score ≥4 are as follows: TALTZ, n = 83; PBO,
n = 40.

TALTZb
(N=115)
n (%) Placebo
(N=56)
n (%) Week 12    sPGA “0” (clear) or “1” (minimal)c 93 (81%) 6 (11%)    sPGA “0”
(clear) 60 (52%) 1 (2%)    PASI 75c 102 (89%) 14 (25%)    PASI 90 90 (78%) 3
(5%)    PASI 100 57 (50%) 1 (2%)    Itch NRS (≥4 point improvement)d 59 (71%) 8
(20%) Week 4    sPGA “0” (clear) or “1” (minimal) 55 (48%) 4 (7%)    PASI 75 62
(54%) 5 (9%)


14.3 PSORIATIC ARTHRITIS

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.

Clinical Response

In both studies, patients treated with TALTZ 80 mg Q4W demonstrated a greater
clinical response including ACR20, ACR50, and ACR70 compared to placebo at Week
24 (Table 6). In PsA2, responses were seen regardless of prior anti-TNFα
exposure.

Table 6: Responsesa at Week 12 and 24; NRIb

a Patients who met escape criteria (less than 20% improvement in tender and
swollen joint counts) at Week 16 or had missing data at Week 24 were considered
non-responders at Week 24.

b Abbreviations: N = number of patients in the intent-to-treat population; NRI =
Non-Responder Imputation.

c At Week 0, patients received 160 mg of TALTZ.

PsA1 – anti-TNFα naive PsA2 – anti-TNFα – experienced TALTZ
80 mgc
Q4W
(N=107) Placebo (N=106) Difference from placebo (95% CI) TALTZ
80 mgc
Q4W
(N=122) Placebo (N=118) Difference from placebo (95% CI) ACR20 response Week 12
(%) 57 31 26 (13, 39) 50 22 28 (16, 40) Week 24 (%) 58 30 28 (15, 41) 53 20 34
(22, 45) ACR50 response Week 12 (%) 34 5 29 (19, 39) 31 3 28 (19, 37) Week 24
(%) 40 15 25 (14, 37) 35 5 30 (21, 40) ACR70 response Week 12 (%) 15 0 15 (8,
22) 15 2 13 (6, 20) Week 24 (%) 23 6 18 (9, 27) 22 0 22 (15, 30)

The percentage of patients achieving ACR20 response by visit is shown in Figure
1.

Figure 1: Percent of Patients Achieving ACR20 Responsea in PsA1 Through Week 24



a Patients who met escape criteria (less than 20% improvement in tender and
swollen joint counts) at Week 16 or had missing data at Week 24 were considered
non-responders at Week 24.

The improvements in the components of the ACR response criteria are shown in
Table 7.

Table 7: Efficacy results in ACR Components at Week 12 and 16

a At Week 0, subjects received 160 mg of TALTZ.

b Disability Index of the Health Assessment Questionnaire; 0 = best, 3 = worst,
measures the patient's ability to perform the following: dress/groom, arise,
eat, walk, reach, grip, maintain hygiene, and maintain daily activity.

PsA1 PsA2 TALTZ 80 mga
Q4W (N=107) Placebo
(N=106) TALTZ 80 mga
Q4W (N=122) Placebo
(N=118) No. of Swollen Joints      Baseline 11.4 10.6 13.1 10.3      Mean Change
at Week 12 -6.2 -3.2 -5.8 -2.6      Mean Change at Week 16 -6.2 -3.0 -7.4 -2.6
No. of Tender Joints      Baseline 20.5 19.2 22.0 23.0      Mean Change at Week
12 -10.3 -3.5 -9.4 -5.4      Mean Change at Week 16 -9.7 -4.0 -10.1 -3.0
Patient's Assessment of Pain      Baseline 60.1 58.5 63.9 63.9      Mean Change
at Week 12 -26.6 -9.1 -29.8 -11.9      Mean Change at Week 16 -26.1 -10.6 -30.1
-12.3 Patient Global Assessment      Baseline 62.7 61.1 66.4 64.1      Mean
Change at Week 12 -29.7 -11.1 -34.5 -10.7      Mean Change at Week 16 -30.4
-13.2 -35.3 -15.7 Physician Global Assessment      Baseline 57.6 55.9 60.3 58.9
     Mean Change at Week 12 -34.0 -16.6 -34.4 -15.9      Mean Change at Week 16
-35.5 -16.5 -32.9 -9.7 Disability Index (HAQ-DI)b      Baseline 1.2 1.2 1.2 1.2
     Mean Change at Week 12 -0.4 -0.1 -0.4 -0.1      Mean Change at Week 16 -0.4
-0.1 -0.5 -0.1 CRP (mg/L)      Baseline 12.8 15.1 17.0 12.1      Mean Change at
Week 12 -8.8 -3.2 -11.4 -4.3      Mean Change at Week 16 -9.3 -3.2 -11.2 -5.9

Treatment with TALTZ resulted in improvement in dactylitis and enthesitis in
patients with pre-existing dactylitis or enthesitis.

Treatment with TALTZ 80 mg Q4W resulted in an improvement in psoriatic skin
lesions in patients with PsA.

Radiographic Response

Radiographic changes were assessed in PsA1. Inhibition of progression of
structural damage was assessed radiographically and expressed as the change in
modified total Sharp score (mTSS) at Week 16, compared to baseline. The total
Sharp score was modified for psoriatic arthritis by addition of hand distal
interphalangeal (DIP) joints.

TALTZ 80 mg Q4W inhibited the progression of structural joint damage (mTSS)
compared to placebo at Week 16. The adjusted mean change from baseline in the
mTSS was 0.13 for TALTZ 80 mg Q4W and 0.36 for placebo (difference in means
TALTZ minus placebo: -0.23, 95% CI: (-0.42, -0.04)).

Physical Function

TALTZ treated patients showed improvement in physical function compared to
patients treated with placebo as assessed by the Health Assessment
Questionnaire-Disability Index (HAQ-DI) at Week 12 and 24. In both studies, the
proportion of HAQ-DI responders (≥0.35 improvement in HAQ-DI score) was greater
in the TALTZ 80 mg Q4W groups compared to placebo at week 12 and 24.

Other Health-Related Outcomes

General health status was assessed by the Short Form health survey (SF-36). At
Week 12 in PsA1 and PsA2, patients treated with TALTZ showed greater improvement
from baseline in the SF-36 physical component summary (PCS) score compared to
patients treated with placebo but this improvement was not consistent in both
studies for the SF-36 mental component summary (MCS) score. At Week 12, there
was consistent evidence of effect in the physical-functioning, role-physical,
bodily-pain, and general health domains but not in the social-functioning,
role-emotional, vitality, and mental health domains.


14.4 ANKYLOSING SPONDYLITIS

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.

Clinical Response

In both studies, patients treated with TALTZ 80 mg Q4W demonstrated greater
improvements in ASAS40 and ASAS20 responses compared to placebo at Week 16
(Table 8). Responses were seen regardless of concomitant therapies. In AS2,
responses were seen regardless of prior TNF-inhibitor exposure.

Table 8: ASAS20 and ASAS40 Responses at Week 16, NRIa,b

a Abbreviations: N = number of patients in the intent-to-treat population; NRI =
Non-responder Imputation.

b Patients with missing data were counted as non-responders.

c At Week 0, patients received 80 mg or 160 mg of TALTZ.

d An ASAS20 response is defined as a ≥20% improvement and an absolute
improvement from baseline of ≥1 units (range 0 to 10) in ≥3 of 4 domains
(Patient Global, Spinal Pain, Function, and Inflammation), and no worsening of
≥20% and ≥1 unit (range 0 to 10) in the remaining domain. An ASAS40 response is
defined as a ≥40% improvement and an absolute improvement from baseline of ≥2
units in ≥3 of 4 domains without any worsening in the remaining domain.

e Primary endpoint.

AS1 – biologic-naive AS2 – TNF-inhibitor experienced TALTZ
80 mg
Q4Wc
(N=81) Placebo (N=87) Difference from placebo (95% CI) TALTZ
80 mg
Q4Wc
(N=114) Placebo (N=104) Difference from placebo (95% CI) ASAS20 responsed, % 64
40 24 (9, 39) 48 30 18 (6, 31) ASAS40 responsed,e, % 48 18 30 (16, 43) 25 13 13
(3, 23)

The percent of patients achieving ASAS40 response by visit in AS1 is shown in
Figure 2.

Figure 2: ASAS40 Response through Week 16, NRIa



a Patients with missing data were counted as non-responders.

The improvement in the main components of the ASAS40 response criteria and other
measures of disease activity are shown in Table 9.

Table 9: ASAS Components and Other Measures of Disease Activity at Week 16a,b

a Abbreviations: ASDAS = Ankylosing Spondylitis Disease Activity Score; BASDAI =
Bath Ankylosing Spondylitis Disease Activity Index; BASFI = Bath Ankylosing
Spondylitis Functional Index; BASMI = Bath Ankylosing Spondylitis Metrology
Index; hsCRP = High sensitivity C-reactive protein.

b Mean changes are least-squares mean changes from baseline at Week 16.

c At Week 0, patients received 80 or 160 mg of TALTZ.

d Inflammation is the mean of patient-reported stiffness self-assessments
(questions 5 and 6) in BASDAI.

AS1 – biologic-naive AS2 – TNF-inhibitor experienced TALTZ 80 mg
Q4Wc (N=81) Placebo
(N=87) TALTZ 80 mg
Q4Wc (N=114) Placebo
(N=104) ASAS Components      Patient Global Assessment (0-10)          
 Baseline 6.9 7.1 8.0 7.8            Mean Change from Baseline -2.5 -1.4 -2.4
-0.7      Total Spinal Pain (0-10)            Baseline 7.2 7.4 7.9 7.8          
 Mean Change from Baseline -3.2 -1.7 -2.4 -1.0      BASFI (0-10)          
 Baseline 6.1 6.4 7.4 7.0            Mean Change from Baseline -2.4 -1.2 -1.7
-0.6      Inflammation (0-10)d            Baseline 6.5 6.8 7.2 7.2          
 Mean Change from Baseline -3.2 -1.3 -2.4 -0.7 Other Measures of Disease
Activity      BASDAI Score            Baseline 6.8 6.8 7.5 7.3            Mean
Change from Baseline -2.9 -1.4 -2.2 -0.9      BASMI            Baseline 3.9 4.5
4.7 4.9            Mean Change from Baseline -0.5 -0.1 -0.3 -0.0      hsCRP
(mg/L)            Baseline 12.2 16.0 20.2 16.0            Mean Change from
Baseline -5.2 1.4 -11.1 9.7

Health-Related Outcomes

General health status and quality of life was assessed by the Short Form health
survey (SF-36). At Week 16, in AS1 and AS2, compared to placebo, patients
treated with TALTZ showed greater improvement from baseline in the SF-36
physical component summary (PCS) score and the physical functioning, role
physical, bodily pain, vitality, and general health domains, with no consistent
improvements in the mental component summary (MCS), social functioning, role
emotional, and mental health domains.


14.5 NON-RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS

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 sacroilitis 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.

Clinical Response

At both Weeks 16 and 52, a greater proportion of patients treated with TALTZ
80 mg Q4W had ASAS40 response compared to patients treated with placebo (Table
10). The components of ASAS response criteria and CRP are shown in Table 11.

Table 10: ASAS40 Responses at Week 16 and Week 52, NRIa,b

a Abbreviations: N = number of patients in the intent-to-treat population; NRI =
Non-responder Imputation.

b Patients who initiated open-label TALTZ 80 mg Q2W, or discontinued initially
randomized treatment and remained in the study, or were missing Week 16 or Week
52 data were counted as non-responders.

c Starting at Week 16 and up to Week 44, patients who were determined as
inadequate responders by investigators were given the option to make changes in
their background therapy and/or transition to open label TALTZ 80 mg Q2W.

d At Week 0, patients received 80 mg or 160 mg of TALTZ.

e An ASAS40 response is defined as a ≥40% improvement and an absolute
improvement from baseline of ≥2 units in ≥3 of 4 domains without any worsening
in the remaining domain.

Week 16 Week 52 TALTZ
80 mg
Q4Wc,d
(N=96) Placebo (N=105) Difference from placebo (95% CI) TALTZ
80 mg
Q4Wc,d
(N=96) Placebo (N=105) Difference from placebo (95% CI) ASAS40 responsee, % 35.4
19.0 16.4 (4.2, 28.5) 30.2 13.3 16.9 (5.6, 28.1)

The improvement in the main components of the ASAS40 response criteria and other
measures of disease activity at Week 16 are shown in Table 11.

Table 11: ASAS Components and Other Measures of Disease Activity at Week 16a

a Abbreviations: BASDAI = Bath Ankylosing Spondylitis Disease Activity Index;
BASFI = Bath Ankylosing Spondylitis Functional Index; BASMI = Bath Ankylosing
Spondylitis Metrology Index; hsCRP = High sensitivity C-reactive protein; NRI =
Non-responder Imputation.

b At Week 0, patients received 80 or 160 mg of TALTZ.

c Mean changes are least-squares mean changes from baseline at Week 16 using a
mixed model for repeated measures adjusting for treatment group, screening
MRI/CRP classification, visit, continuous baseline, interaction of visit with
treatment, interaction of continuous baseline with visit.

d Inflammation is the mean of patient-reported stiffness self-assessments
(questions 5 and 6) in BASDAI questionnaire.

TALTZ 80 mg
Q4Wb (N=96) Placebo
(N=105) ASAS Components      Patient Global Assessment (0-10)          
 Baseline 7.1 7.4            Mean Change from Baselinec -2.3 -1.3      Total
Spinal Pain (0-10)            Baseline 7.3 7.4            Mean Change from
Baselinec -2.4 -1.5      BASFI (0-10)            Baseline 6.4 6.7          
 Mean Change from Baselinec -2.0 -1.3      Inflammation (0-10)d          
 Baseline 6.8 7.0            Mean Change from Baselinec -2.5 -1.5 Other Measures
of Disease Activity      BASDAI Score (0-10)            Baseline 7.0 7.2        
   Mean Change from Baselinec -2.2 -1.5      BASMI (0-10)            Baseline
3.2 3.2            Mean Change from Baselinec -0.4 -0.2      hsCRP (mg/L)      
     Baseline 12.4 14.3            Mean Change from Baselinec -8.0 -3.0

The percent of patients achieving ASAS40 responses by visit is shown in Figure
3.



Figure 3: ASAS40 Responses through Week 16, NRIa



a Patients with missing data were counted as non-responders.

Health-Related Outcomes

General health status and quality of life was assessed by the Short Form health
survey (SF-36). At Week 16, compared to placebo, nr-axSpA patients treated with
TALTZ 80 mg Q4W showed greater improvement from baseline in the SF-36 physical
component summary (PCS) score and physical functioning, bodily pain, vitality,
and social functioning domains, with no consistent improvements in the mental
component summary (MCS), role physical, general health, role emotional, and
mental health domains.

Hide


+16 HOW SUPPLIED/STORAGE AND HANDLING


16 HOW SUPPLIED/STORAGE AND HANDLING


16.1 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.

TALTZ is supplied as:

Pack Size NDC Code Autoinjector      80 mg single-dose Carton of 1 0002-1445-11
     80 mg single-dose Carton of 2 0002-1445-27      80 mg single-dose Carton of
3 0002-1445-09 Prefilled syringe      80 mg single-dose Carton of 1 0002-7724-11


16.2 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.

Hide


+17 PATIENT COUNSELING INFORMATION


17 PATIENT COUNSELING INFORMATION

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

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

Infection: Inform patients that TALTZ may lower the ability of their immune
system to fight infections. Instruct patients of the importance of communicating
any history of infections to the healthcare provider, and contacting their
healthcare provider if they develop any symptoms of infection [see Warnings and
Precautions (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)].

Eli Lilly and Company, Indianapolis, IN 46285, USA
US License Number 1891
Product of Ireland

Copyright © 2016, 2021, Eli Lilly and Company. All rights reserved.

TAL-0010-USPI-20210310

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+MEDICATION GUIDE

This Medication Guide has been approved by the U.S. Food and Drug
Administration.

Revised: May 2020

Medication Guide
TALTZ® (tolts)
(ixekizumab)
injection, for subcutaneous use

What is the most important information I should know about TALTZ?
TALTZ is a medicine that affects your immune system. TALTZ may lower the ability
of your immune system to fight infections and may increase your risk of
infections, which can sometimes become serious.


 * Your healthcare provider should check you for tuberculosis (TB) before you
   start treatment with TALTZ.
 * Your healthcare provider may treat you with medicine for TB before you begin
   treatment with TALTZ if you have a past history of TB or have TB.
 * Your healthcare provider should watch you closely for signs and symptoms of
   TB during and after treatment with TALTZ.

Before starting TALTZ, tell your healthcare provider if you:

 * are being treated for an infection
 * have an infection that does not go away or that keeps coming back
 * have TB or have been in close contact with someone with TB
 * think you have an infection or have symptoms of an infection such as:
   

 * fever, sweats, or chills
 * muscle aches
 * cough
 * shortness of breath
 * blood in your phlegm (mucus)

 * weight loss
 * warm, red, or painful skin or sores on your body
 * diarrhea or stomach pain
 * burning when you urinate or urinate more often than normal

After starting TALTZ, call your healthcare provider right away if you have any
of the symptoms of infection listed above.
Do not use TALTZ if you have any symptoms of infection unless you are instructed
to by your healthcare provider.
See “What are the possible side effects of TALTZ?” for more information about
side effects. What is TALTZ?
TALTZ is a prescription medicine used to treat:

 * people 6 years of age and older with moderate-to-severe plaque psoriasis who
   may benefit from taking injections or pills (systemic therapy) or
   phototherapy (treatment using ultraviolet or UV light).
 * adults with active psoriatic arthritis. TALTZ can be used alone or with the
   medicine methotrexate.
 * adults with active ankylosing spondylitis.
 * adults with active non-radiographic axial spondyloarthritis with objective
   signs of inflammation.

It is not known if TALTZ is safe and effective in children for conditions other
than plaque psoriasis or in children under 6 years of age. Do not use TALTZ if
you have had a severe allergic reaction to ixekizumab or any of the other
ingredients in TALTZ.
See the end of this Medication Guide for a complete list of ingredients in
TALTZ. Before using TALTZ, tell your healthcare provider about all of your
medical conditions, including if you:

 * have any of the conditions or symptoms listed in the section “What is the
   most important information I should know about TALTZ?”
 * have Crohn's disease or ulcerative colitis
 * have recently received or are scheduled to receive an immunization (vaccine).
   You should avoid receiving live vaccines during treatment with TALTZ.
 * are pregnant or plan to become pregnant. It is not known if TALTZ can harm
   your unborn baby.
 * are breastfeeding or plan to breastfeed. It is not known if TALTZ passes into
   your breast milk.

Tell your healthcare provider about all the medicines you take, including
prescription and over-the-counter medicines, vitamins, and herbal supplements.
How should I use TALTZ?
See the detailed “Instructions for Use” that comes with your TALTZ for
information on how to prepare and inject a dose of TALTZ, and how to properly
throw away (dispose of) used TALTZ autoinjectors and prefilled syringes.

 * Use TALTZ exactly as prescribed by your healthcare provider.
 * For children weighing 110 pounds (50 kg) or less, TALTZ must be given by a
   healthcare provider. TALTZ will be given every 4 weeks.
 * For children weighing more than 110 pounds (50 kg), if your healthcare
   provider decides that your caregiver may give your injections of TALTZ at
   home, your caregiver should ask and receive training from the healthcare
   provider on the right way to prepare and inject TALTZ. TALTZ will be given
   every 4 weeks.
 * For adults, if your healthcare provider decides that you or a caregiver may
   give your injections of TALTZ at home, you should receive training on the
   right way to prepare and inject TALTZ. Do not try to inject TALTZ yourself,
   until you or your caregiver have been shown how to inject TALTZ.
 * TALTZ comes in an autoinjector and a prefilled syringe that you or your
   caregiver may use at home to give injections. Your healthcare provider will
   decide which type of TALTZ is best for you to use at home.
 * TALTZ is given as an injection under your skin (subcutaneous injection), in
   your thighs or stomach area (abdomen) by you or a caregiver. A caregiver may
   also give you an injection of TALTZ in the back of your arm.
 * Do not give an injection in an area of the skin that is tender, bruised, red
   or hard, or in an area of skin that is affected by psoriasis.
 * Each TALTZ injection should be given at a different site. Do not use the 1
   inch area around your navel (belly button).

If you forget to take your dose:

 * Do not miss any doses of TALTZ unless your healthcare provider says it is
   okay. If you forget to take your TALTZ dose, inject a dose as soon as you
   remember. Then, take your next dose at your regular scheduled time.
 * If you inject more TALTZ than prescribed, call your healthcare provider or go
   to the nearest emergency room right away.

What are the possible side effects of TALTZ?
TALTZ may cause serious side effects, including:


 * See “What is the most important information I should know about TALTZ?”
 * Serious allergic reactions. If you have a severe allergic reaction, do not
   give another injection of TALTZ. Get emergency medical help right away if you
   get any of the following symptoms of a serious allergic reaction:
   

 * feel faint
 * swelling of your face, eyelids, lips, mouth, tongue, or throat

 * trouble breathing or throat tightness
 * chest tightness
 * skin rash

 * Crohn's disease or ulcerative colitis (inflammatory bowel disease) can happen
   during treatment with TALTZ, including worsening symptoms. Tell your
   healthcare provider if you have new or worsening symptoms of inflammatory
   bowel disease during treatment with TALTZ, including:
   * stomach (abdomen) pain
   * diarrhea with or without blood
   * weight loss

The most common side effects of TALTZ in adults and children include:

 * injection site reactions
 * upper respiratory infections

 * nausea
 * fungal infections

These are not all of the possible side effects of TALTZ. Tell your healthcare
provider about any side effect that bothers you or that does not go away. Call
your doctor for medical advice about side effects. You may report side effects
to FDA at 1-800-FDA-1088. How should I store TALTZ?

 * Protect TALTZ from light.
 * Store TALTZ in the refrigerator between 36°F to 46°F (2°C to 8°C).
   * If needed, you or a caregiver may store TALTZ at room temperature up to
     86°F (30°C) 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. Throw away TALTZ if it is not used within 5 days at room
     temperature.
   * 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. Make sure the unrefrigerated TALTZ is protected from light.
 * Do not freeze TALTZ. Do not use if TALTZ has been frozen.
 * Do not shake TALTZ.

Keep TALTZ and all medicines out of the reach of children. General information
about the safe and effective use of TALTZ.
Medicines are sometimes prescribed for purposes other than those listed in a
Medication Guide. Do not use TALTZ for a condition for which it was not
prescribed. Do not give TALTZ to other people, even if they have the same
symptoms you have. It may harm them. You can ask your healthcare provider or
pharmacist for information about TALTZ that is written for health professionals.
What are the ingredients in TALTZ?
Active ingredient: ixekizumab
Inactive ingredients: Citric Acid Anhydrous, Polysorbate 80, Sodium Chloride,
Sodium Citrate Dihydrate, and Water for Injection
Not made with natural rubber latex.

For more information about TALTZ, call 1-800-545-5979 (1-800-LillyRx) or go to
the following website: www.taltz.com.

TALTZ® (ixekizumab) injection is a registered trademark of Eli Lilly and
Company.
Eli Lilly and Company Indianapolis, IN 46285, USA, US License Number 1891,
Product of Ireland
Copyright © 2016, 2020, Eli Lilly and Company. All rights reserved.
TAL-0006-MG-20200529

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+INSTRUCTIONS FOR USE

INSTRUCTIONS FOR USE TALTZ® (tol(t)s)
(ixekizumab)
injection, for subcutaneous use
Autoinjector
Before you use the TALTZ autoinjector, read and carefully follow all the
step-by-step instructions. Important information:
 * Your healthcare provider or nurse should show you how to prepare and inject
   TALTZ using the autoinjector. Do not inject yourself or someone else until
   you have been shown how to inject TALTZ.

 * You and your caregiver should read this Instructions for Use before you start
   using TALTZ and each time you get a refill. Keep the Instructions for Use and
   refer to them as needed.

 * Each TALTZ autoinjector contains 1 dose of TALTZ. The autoinjector is for
   one-time use only.

 * The autoinjector contains glass parts. Handle autoinjector carefully. If you
   drop it on a hard surface, do not use it. Use a new TALTZ autoinjector for
   your injection.

 * Your healthcare provider may help you decide where on your body to inject
   your dose. Do not give an injection in an area of the skin that is tender,
   bruised, red or hard, or in an area of skin that is affected by psoriasis.
   Read the “Choose your injection site” section of these instructions to help
   you choose which area can work best for you.

 * If you have vision or hearing problems, do not use TALTZ autoinjector without
   help from a caregiver.

INSTRUCTIONS FOR USE
Before you use the TALTZ autoinjector, read and carefully follow all the
step-by-step instructions. Parts of the TALTZ autoinjector 1 Get Ready
1a

 * Take the TALTZ autoinjector from the refrigerator.
 * Remove the autoinjector from the package. Put the original package with any
   unused autoinjectors back in the refrigerator.
 * Leave the base cap on until you are ready to inject.
 * Wait 30 minutes to let the autoinjector warm to room temperature before you
   use it.
 * Do not microwave the autoinjector, run hot water over it, or leave it in
   direct sunlight.
 * Do not shake the autoinjector.


1b Gather the supplies needed for your injection:

 * 1 alcohol wipe
 * 1 cotton ball or piece of gauze
 * 1 sharps disposal container. See “Dispose of the used autoinjector.”


1c
Inspect the autoinjector.

 * Make sure the name TALTZ appears on the label.
 * The medicine inside should be clear. Its color may be colorless to slightly
   yellow.

Do not use the autoinjector, and dispose of as directed by your healthcare
provider or pharmacist if:

 * the expiration date printed on the label has passed.
 * it looks damaged.
 * the medicine is frozen.
 * the medicine is cloudy, discolored, or has small particles. The medicine
   should look clear and colorless to slightly yellow.


1d
Wash your hands with soap and water before you inject TALTZ.
1e



Choose your injection site.


You may inject in your stomach area (abdomen) or in your thigh, or in the back
of your arm. To inject in your arm, you will need someone to help you.
Do not give an injection into areas where the skin is tender, bruised, red or
hard, or in an area of skin that is affected by psoriasis.
Do not inject within 1 inch of the navel (belly button).
Alternate your injection sites.

 * Do not inject in the exact same spot every time. For example, if your last
   injection was in your left thigh, your next injection should be in your right
   thigh, your abdomen, or the back of either arm.
 * Talk with your healthcare provider about where on your body to best inject
   TALTZ.


1f
Prepare your skin. Clean your injection site with an alcohol wipe. Let the
injection site dry before you inject TALTZ.

2 Inject TALTZ
2a

Make sure the lock ring is in the lock position.

 * Leave the base cap on until you are ready to inject.
 * Do not touch the needle.

Twist off the base cap in the direction of the arrows.
 * Throw the base cap in the trash. You will not need to put the base cap back
   on. If you do, you could damage the needle or stick yourself by accident.


2b

Place the clear base flat and firmly against your skin at the injection site.
2c

While holding the clear base against your skin, turn the lock ring to the unlock
position. You are now ready to inject.
2d
Press the green injection button. There will be a loud click.

 * Keep holding the clear base firmly against your skin.
 * You will hear a second click in about 10 seconds after the first one. The
   second click tells you that your injection is complete.
 * You will see the gray plunger at the top of the clear base.

Remove the autoinjector from your skin.
 * Press a cotton ball or gauze over the injection site. Do not rub the
   injection site, as this may cause bruising. You may have slight bleeding.
   This is normal.
   

Do not put the base cap back on the autoinjector.
3


Dispose of (throw away) the used autoinjector.


3a

 * Put the used TALTZ autoinjector in a FDA-cleared sharps disposal container
   right away after use. Do not throw away (dispose of) the TALTZ autoinjector
   in your household trash.

 * If you do not have a FDA-cleared sharps disposal container, you may use a
   household container that is:
   * made of a heavy-duty plastic,
   * can be closed with a tight-fitting, puncture-resistant lid, without sharps
     being able to come out,
   * upright and stable during use,
   * leak-resistant, and
   * properly labeled to warn of hazardous waste inside the container.

 * When your sharps disposal container is almost full, you will need to follow
   your community guidelines for the right way to dispose of your sharps
   disposal container. There may be state or local laws about how you should
   throw away needles and syringes. For more information about safe sharps
   disposal, and for specific information about sharps disposal in the state you
   live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal

 * Do not recycle your used sharps disposal container.

Commonly asked questions and answers.   Q. What if I see bubbles in the TALTZ
autoinjector? A. It is normal to have air bubbles in the autoinjector.   Q. What
if there is a drop of liquid on the tip of the needle when I remove the base
cap? A. It is okay to see a drop of liquid on the tip of the needle.   Q. What
if I unlocked the autoinjector and pressed the green injection button before I
twisted off the base cap? A. Do not remove the base cap. Dispose of the
autoinjector and get a new one.   Q. Do I need to hold the injection button down
until the injection is complete? A. You do not need to hold the injection button
down, but it may help you keep the autoinjector steady and firm against your
skin.   Q. What if the needle did not retract after my injection or I am not
sure that the autoinjector worked in the right way? A. Do not touch the needle
or replace the base cap. Store the autoinjector in a safe place (e.g., a
household container as described in “Dispose of the used autoinjector.”) to
avoid an accidental needlestick and contact Lilly (1-800-545-5979) for
instructions on how to return the autoinjector.   Q. What if I hear more than 2
clicks during my injection? Did I get my complete dose? A. You may hear a soft
click right before the second loud click. This is the normal operation of the
autoinjector. Do not remove the autoinjector from your skin until you hear the
second loud click.   Q. How can I tell if my injection is complete? A. After you
press the green injection button, you will hear 2 loud clicks. The second click
tells you that your injection is complete. You will also see the gray plunger at
the top of the clear base.   Q. What if the autoinjector is left at room
temperature for longer than 30 minutes? A. If needed, the autoinjector may be
left out of the refrigerator at room temperature up to 86°F (30°C) for up to 5
days if protected from light. Throw away TALTZ if not used within the 5-day
period at room temperature. See "How should I store TALTZ autoinjector?" for
more detail.   If you have more questions about how to use the TALTZ
autoinjector:
 * Call your healthcare provider
 * Call Lilly at 1-800-545-5979 (1-800-Lilly-Rx)

 * Visit www.taltz.com       

 

How should I store TALTZ autoinjector?
 * Protect TALTZ from light.

 * Store TALTZ in the refrigerator between 36°F to 46°F (2°C to 8°C).
   * If needed, you or a caregiver may store TALTZ at room temperature up to
     86°F (30°C) 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. Throw away TALTZ if it is not used within 5 days at room
     temperature.
   * 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 TALTZ. Do not use if TALTZ has been frozen.

 * Do not shake TALTZ.

Keep TALTZ and all medicines out of the reach of children.   Read the full
Prescribing Information and Medication Guide for TALTZ inside this box to learn
more about your medicine.

This Instructions for Use has been approved by the U.S. Food and Drug
Administration.




Eli Lilly and Company

Indianapolis, IN 46285, USA

US License Number 1891

TALTZ is a trademark of Eli Lilly and Company.

Copyright © 2016, 2021, Eli Lilly and Company. All rights reserved.

The TALTZ autoinjector meets the current dose accuracy and functional
requirements of ISO 11608-1 and 11608-5.

TALAI-0007-IFU-20210622

Revised: June 2021

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+INSTRUCTIONS FOR USE

INSTRUCTIONS FOR USE TALTZ® (tol(t)s)
(ixekizumab)
injection, for subcutaneous use
Prefilled Syringe
Before you use the TALTZ prefilled syringe, read and carefully follow all the
step-by-step instructions. Important information:
 * Your healthcare provider or nurse should show you how to prepare and inject
   TALTZ using the prefilled syringe. Do not inject yourself or someone else
   until you have been shown how to inject TALTZ.

 * You and your caregiver should read this Instructions for Use before you start
   using TALTZ and each time you get a refill. Keep the Instructions for Use and
   refer to them as needed.

 * Each TALTZ prefilled syringe contains 1 dose of TALTZ. The syringe is for
   one-time use only. Do not share or reuse your TALTZ prefilled syringe. You
   may give or get an infection.

 * Your healthcare provider may help you decide where on your body to inject
   your dose. Do not give an injection in an area of the skin that is tender,
   bruised, red or hard, or in an area of skin that is affected by psoriasis.
   Read the “Choose your injection site” section of these instructions to help
   you choose which area can work best for you.

 * If you have vision problems, do not use TALTZ prefilled syringe without help
   from a caregiver.

INSTRUCTIONS FOR USE
Before you use the TALTZ prefilled syringe, read and carefully follow all the
step-by-step instructions. Parts of the TALTZ prefilled syringe     1 Get Ready
 
1a

 * Take the TALTZ prefilled syringe from the refrigerator.
 * Remove the prefilled syringe from the package. Put the original package with
   any unused syringes back in the refrigerator.
 * Leave the needle cap on the syringe until you are ready to inject.
 * Wait 30 minutes to let the prefilled syringe warm to room temperature before
   you use it.
 * Do not microwave the syringe, run hot water over it, or leave it in direct
   sunlight.
 * Do not shake the prefilled syringe.

  1b Gather the supplies needed for your injection:

 * 1 alcohol wipe
 * 1 cotton ball or piece of gauze
 * 1 sharps disposal container. See “Dispose of the used prefilled syringe.”

  1c Inspect the syringe. Leave the needle cap on the syringe until you are
ready to inject.

 * Make sure the name TALTZ appears on the label.
 * The medicine inside should be clear. Its color may be colorless to slightly
   yellow.

Do not use the prefilled syringe, and dispose of as directed by your healthcare
provider or pharmacist if:

 * the expiration date printed on the label has passed.
 * it looks damaged.
 * the medicine is frozen.
 * the medicine is cloudy, discolored, or has small particles. The medicine
   should look clear and colorless to slightly yellow.

  1d Wash your hands with soap and water before you inject TALTZ.   1e

Choose your injection site.


You may inject in your stomach area (abdomen) or in your thigh, or in the back
of your arm. To inject in your arm, you will need someone to help you.
Do not give an injection into areas where the skin is tender, bruised, red or
hard, or in an area of skin that is affected by psoriasis.
Do not inject within 1 inch of the navel (belly button).
Alternate your injection sites.

 * Do not inject in the exact same spot every time. For example, if your last
   injection was in your left thigh, your next injection should be in your right
   thigh, your abdomen, or the back of either arm.
 * Talk with your healthcare provider about where on your body to best inject
   TALTZ.

  1f Prepare your skin. Clean your injection site with an alcohol wipe. Let the
injection site dry before you inject TALTZ.   2 Inject TALTZ  
2a

Pull the needle cap off and throw it away.

 * Do not put the needle cap back on. You could damage the needle or stick
   yourself by accident.
 * Do not touch the needle.

 
2b

Gently pinch and hold a fold of skin where you will inject.  
2c



Insert the needle at a 45-degree angle. Then gently let go of your skin. Make
sure to keep the needle in place.

Let go of your skin before you push the plunger in.

  2d Push in the plunger.

 * Slowly push on the thumb pad to push the plunger all the way in until all the
   medicine is injected.
 * The gray syringe plunger should be pushed all the way to the needle end of
   the syringe.
 * You should see the green plunger rod show through the syringe body when the
   injection is complete.
 * Gently remove the needle from your skin.
 * Press a cotton ball or gauze over the injection site. Do not rub the
   injection site, as this may cause bruising. You may have slight bleeding.
   This is normal.

Do not put the needle cap back on the prefilled syringe.
  3

Dispose of (throw away) the used prefilled syringe.

 
3a

 * Put the used TALTZ prefilled syringe in a FDA-cleared sharps disposal
   container right away after use. Do not throw away (dispose of) the TALTZ
   prefilled syringe in your household trash.

 * If you do not have a FDA-cleared sharps disposal container, you may use a
   household container that is:
   * made of a heavy-duty plastic,
   * can be closed with a tight-fitting, puncture-resistant lid, without sharps
     being able to come out,
   * upright and stable during use,
   * leak-resistant, and
   * properly labeled to warn of hazardous waste inside the container.

 * When your sharps disposal container is almost full, you will need to follow
   your community guidelines for the right way to dispose of your sharps
   disposal container. There may be state or local laws about how you should
   throw away needles and syringes. For more information about safe sharps
   disposal, and for specific information about sharps disposal in the state you
   live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal

 * Do not recycle your used sharps disposal container.

  Commonly asked questions and answers.   Q. What if I see air bubbles in my
TALTZ prefilled syringe? A. It is normal to have air bubbles in the prefilled
syringe.   Q. What if there is a drop of liquid on the tip of the needle when I
remove the needle cap? A. It is okay to see a drop of liquid on the tip of the
needle.   Q. What if I cannot push in the plunger? A. If the plunger is stuck or
damaged:
 * Do not continue to use the syringe

 * Remove the needle from your skin

 * Dispose of the syringe and get a new one

  Q. How can I tell if my injection is complete? A. When your injection is
complete:
 * The green plunger rod should show through the body of the syringe.

 * The gray syringe plunger should be pushed all the way to the needle end of
   the syringe.

  Q. What if the syringe is left at room temperature for longer than 30 minutes?
A. If needed, the syringe may be left out of the refrigerator at room
temperature up to 86°F (30°C) for up to 5 days if protected from light. Throw
away TALTZ if not used within the 5-day period at room temperature. See "How
should I store TALTZ prefilled syringe?" for more detail.

If you have more questions about how to use the TALTZ prefilled syringe:
 * Call your healthcare provider
 * Call Lilly at 1-800-545-5979 (1-800-Lilly-Rx)

 * Visit www.taltz.com       

  How should I store TALTZ prefilled syringe?
 * Protect TALTZ from light.

 * Store TALTZ in the refrigerator between 36°F to 46°F (2°C to 8°C).
   * If needed, you or a caregiver may store TALTZ at room temperature up to
     86°F (30°C) 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. Throw away TALTZ if it is not used within 5 days at room
     temperature.
   * Record the date when TALTZ is first removed from the refrigerator in the
     spaces provided on the carton.

 * Do not freeze TALTZ. Do not use if TALTZ has been frozen.

 * Do not shake TALTZ.

Keep TALTZ and all medicines out of the reach of children.   Read the full
Prescribing Information and Medication Guide for TALTZ inside this box to learn
more about your medicine.

This Instructions for Use has been approved by the U.S. Food and Drug
Administration.




Eli Lilly and Company

Indianapolis, IN 46285, USA

US License Number 1891

TALTZ is a trademark of Eli Lilly and Company.

Copyright © 2016, 2021, Eli Lilly and Company. All rights reserved.

TALPFS-0005-IFU-20210622

Revised: June 2021

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Revised: 6/2021
Document Id: 15a3096a-9d04-4af3-8feb-4df823e6878e
34391-3
Set id: ac96658a-d7dc-4c7c-8928-2adcdf4318b2
Version: 27
Effective Time: 20210622
Eli Lilly and Company
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