Taltz

Pregnancy

There are no available data regarding use in pregnant women to inform any drug-associated risks

Human IgG is known to cross the placental barrier; therefore, ixekizumab may be transmitted from the mother to the developing fetus

Animal studies

• Unknown if distributed in human breast milk
• Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

Lactation

Unknown if distributed in human breast milk

Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

• Solution for injection: 80 mg/ml single-dose prefilled autoinjector or prefilled syringe.

• This drug should be refrigerated at 2 C - 8 C (36 F - 46 F) and it should not be frozen.
• The single-dose autoinjector or syringe should be discarded in a puncture-resistant container after use.

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, US (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.

See the detailed Instructions for Use that comes with your prescription for information on how to prepare and inject a dose of Taltz, and how to properly throw away (dispose of) the used autoinjectors and prefilled syringes.

• Use Taltz exactly as prescribed by your healthcare provider.
• 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 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 the 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 injection should be given at an alternate site. Do not use the one inch area around your navel (belly button).

If you forget to take your dose:

• Do not miss any doses unless your healthcare provider says it is okay. If you forget to take your 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.

In the U.S.

• Taltz

Available Dosage Forms:

• Solution

Therapeutic Class: Antipsoriatic

Pharmacologic Class: Monoclonal Antibody

In the event of overdosage, monitor the patient for any signs or symptoms of adverse reactions and institute appropriate symptomatic treatment immediately.

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.

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.

Pharmacodynamics

No formal pharmacodynamic studies have been conducted with Taltz.

Pharmacokinetics

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.

Renal or Hepatic Impairment

No formal trial of the effect of hepatic or renal impairment on the pharmacokinetics of ixekizumab was conducted.

Drug Interaction Studies

Drug interaction studies have not been conducted with Taltz.

Three multicenter, randomized, double-blind, placebo-controlled trials (Trials 1, 2, and 3) 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 two 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 2.

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.

Subjects treated with Taltz 80 mg Q2W experienced improvement in itch severity when compared to placebo 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 four 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.

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:

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).
• 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.

Taltz (ixekizumab) is an immunosuppressant that reduces the effects of a chemical substance in the body that can cause inflammation.

Taltz is used to treat moderate to severe plaque psoriasis (raised, silvery flaking of the skin) in adults.

Taltz may also be used for purposes not listed in this medication guide.