Taltz (ixekizumab) - 4 indications

Scroll down for information on each indication:

• for the treatment of patients aged 6 years or older with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy; approved March 2016 for adults, approval expanded March 2020 to include pediatrics
• for the treatment of adults with active psoriatic arthritis; approved December 2017
• for the treatment of active ankylosing spondylitis; approved August 2019
• for the treatment of active non-radiographic axial spondyloarthritis; approved June of 2020

General Information

Taltz (ixekizumab) a humanized interleukin-17A antagonist.

Taltz is specifically indicated for the following conditions:

• 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
• for the treatment of adult patients with active psoriatic arthritis
• for the treatment of adult patients with active ankylosing spondylitis
• for the treatment of adult patients with active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation

Taltz is supplied as an injection for subcutaneous administration. Scroll down for the recommended dosing/administration for each indication.

Mechanism of Action

Taltz (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. 

Side effects

Adverse effects associated with the use of Taltz may include, but are not limited to, the following:

• injection site reactions
• upper respiratory tract infections
• nausea
• tinea infections

Indication 1 - patients aged 6 years or older with moderate to severe plaque psoriasis

approved March 2016 for adults, approval expanded March 2020 to include pediatrics

Dosing/Administration

Adults: 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.

Pediatrics:  The recommended dose in pediatric patients from 6 to less than 18 years of age is based on the following weight categories.

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

 

Clinical Trial Results

Adults: The FDA approval of Taltz was based on three phase III trials conducted in over 3,800 subjects with moderate-to-severe plaque psoriasis from 21 countries. The three double-blind, multicenter studies, UNCOVER-1, UNCOVER-2 and UNCOVER-3, evaluated the safety and efficacy of Taltz (80 mg every two weeks, following a 160-mg starting dose) compared to placebo after 12 weeks. UNCOVER-2 and UNCOVER-3 included an additional comparator arm in which patients received U.S.-approved etanercept (50 mg twice a week) for 12 weeks. UNCOVER-1 and UNCOVER-2 also evaluated response rates with Taltz during the maintenance period through 60 weeks. In these studies, the co-primary efficacy endpoints at 12 weeks were a 75 percent improvement in the composite Psoriasis Area Severity Index (PASI) score and static Physician's Global Assessment (sPGA) 0 or 1 and at least a 2-point improvement from baseline. In all three studies, at 12 weeks, 87 to 90 percent of patients treated with Taltz saw a significant improvement of their psoriasis plaques (PASI 75). In addition, 81 to 83 percent of patients treated with Taltz achieved sPGA 0 or 1. The majority of patients treated with Taltz, 68 to 71 percent, achieved virtually clear skin (PASI 90) and 35 to 42 percent of patients saw complete resolution of their psoriasis plaques (PASI 100, sPGA 0). Among those patients treated with placebo, 7 percent or fewer achieved PASI 75, 7 percent or fewer achieved sPGA 0 or 1, 3 percent or fewer achieved PASI 90 and 1 percent or fewer achieved PASI 100 and sPGA 0. In UNCOVER-1 and UNCOVER-2, of patients who responded to Taltz (sPGA 0 or 1 and at least a 2-point improvement from baseline) at 12 weeks, 75 percent consistently maintained that response at the 60-week endpoint. Taltz was also statistically superior to etanercept at all skin clearance levels, including PASI 75 and sPGA 0 or 1 at 12 weeks. In an integrated analysis of the U.S. sites in the two active comparator studies, UNCOVER-2 and UNCOVER-3, the respective response rates for Taltz vs. etanercept were 87% vs. 41% for PASI 75 and 73% vs. 27% for sPGA 0 or 1.

Pediatrics: A randomized, double-blind, multicenter, placebo-controlled trial (IXORA-Peds) 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. sPGA score was reached by 81% of the Taltz treatment group versus 11% of the placebo group. PASI75 was reached by 89% of the Taltz arm versus 25% of the placebo arm. 

Indication 2- adults with active psoriatic arthritis

approved December 2017

Dosing/Administration

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.

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

Clinical Trial Results

The FDA approval of Taltz for psoriatic arthritis was based on two randomized, double-blind, placebo-controlled studies (PsA1 and PsA2) in adults, 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. PsA1 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 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. In both studies, patients treated with Taltz 80 mg Q2W or 80 mg Q4W demonstrated a greater clinical response including ACR20, ACR50, and ACR70 compared to placebo at Week 24. In PsA2, responses were seen regardless of prior anti-TNFα exposure.

Indication 3 - adults with active ankylosing spondylitis

approved August 2019

Dosing/Administration

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

Clinical Trial Results

The FDA approval of Taltz for Ankylosing Spondylitis was based on two randomized, double-blind, placebo-controlled Phase 3 studies that included 657 adult patients with active AS: COAST-V in patients who are biologic disease-modifying antirheumatic drug (bDMARD)-naïve and COAST-W in patients who previously had an inadequate response or were intolerant to tumor necrosis factor (TNF) inhibitors.

In both studies, the primary efficacy endpoint was the proportion of patients at 16 weeks achieving Assessment of Spondyloarthritis International Society 40 (ASAS40) response compared to placebo. ASAS40 measures disease signs and symptoms such as pain, inflammation and function. Results from both studies demonstrated that patients treated with Taltz achieved statistically significant and clinically meaningful improvements in signs and symptoms, as defined by ASAS40 response, compared to placebo. At 16 weeks, patients achieved ASAS40 at the following response rates:

• COAST-V: 48 percent of patients treated with Taltz every four weeks versus 18 percent of patients treated with placebo
• COAST-W: 25 percent of patients treated with Taltz every four weeks versus 13 percent of patients treated with placebo

Additionally, patients treated with Taltz demonstrated statistically significant improvements in key secondary endpoints in both studies, including the proportion of patients at 16 weeks achieving ASAS20 at the following response rates:

• COAST-V: 64 percent of patients treated with Taltz every four weeks versus 40 percent of patients treated with placebo
• COAST-W: 48 percent of patients treated with Taltz every four weeks versus 30 percent of patients treated with placebo

Indication 4 - adults with active non-radiographic axial spondyloarthritis

approved June of 2020

Dosing/Administration

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

Clinical Trial Results

The FDA Approval of Taltz for nr-axSpA was based on the results from the Phase 3, multicenter, randomized, double-blind, placebo-controlled 52-week study of adult patients with active nr-axSpA with objective signs of inflammation. The primary endpoint of the study was the proportion of patients achieving ASAS40 at Week 52. The proportion of Taltz patients (n=96) achieving the primary endpoint was superior to placebo (n=105), with 30 percent of patients treated with Taltz 80 mg every four weeks achieving ASAS40 response compared to 13 percent of patients treated with placebo at Week 52. A major secondary endpoint was ASAS40 response at Week 16, with 35 percent of Taltz patients reaching that endpoint compared to 19 percent of placebo patients.