Consumer medicine information

Ilumya

Tildrakizumab

BRAND INFORMATION

Brand name

Ilumya

Active ingredient

Tildrakizumab

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Ilumya.

What is in this leaflet

This leaflet answers some common questions about ILUMYA (pronounced e-loom-e-a).

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking ILUMYA against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist. Keep this leaflet with the medicine, you may need to read it again.

What ILUMYA is used for

ILUMYA is used to treat a skin condition called plaque psoriasis in adults with moderate to severe disease who are candidates for systemic therapy. Plaque psoriasis causes inflammation of the skin. ILUMYA reduces the inflammation and other symptoms of the disease, and promotes skin clearance.

ILUMYA contains the active substance tildrakizumab.

Tildrakizumab is a humanized monoclonal antibody and belongs to a group of medicines called interleukin (IL) inhibitors. This medicine works by neutralising the activity of a protein called IL-23, a substance found in the body which is involved in normal inflammatory and immune responses. In patients with plaque psoriasis, the body produces increased amounts of this protein. This may lead to symptoms such as itching, pain and scaling.

Your doctor may have prescribed it for another reason.

ILUMYA has not been studied in patients under 18 years of age.

ILUMYA may be used in elderly patients aged 65 years and over.

ILUMYA is available only with a doctor’s prescription. It is not addictive.

If you have any questions about how ILUMYA works or why this medicine has been prescribed for you, ask your doctor, pharmacist or nurse.

Before you take ILUMYA

Tell your doctor if you have any of the conditions mentioned below or if you have ever experienced any of these conditions.

When you must not take it

Do not take ILUMYA If:

  • you have had a severe allergic reaction to tildrakizumab or any of the other ingredients listed at the end of this leaflet. (see Product description)
    Some of the symptoms of an allergic reaction may include:
    - shortness of breath
    - wheezing or difficulty breathing
    - swelling of the face, lips, tongue or other parts of the body
    - rash, itching or hives on the skin
    If you think you may be allergic, ask your doctor for advice before using ILUMYA.
  • you have an active infection which your doctor thinks is important.
  • the product appears cloudy, discolored or contains particles.
  • the expiry date on the pack has passed or if packaging is torn or shows signs of tampering. Return expired or damaged stock to your pharmacist.
  • you are not sure whether you should start taking this medicine, talk to your doctor.

Before you start to take it

Tell your doctor before taking ILUMYA if:

  • you currently have an infection or if you have long-term or repeated infections.
  • you have tuberculosis or have been in contact recently with someone who has.
  • you had a recent vaccination or someone close to you has had a vaccination or if you will receive a live vaccine during treatment with ILUMYA. Live vaccines such as oral polio vaccine, should not be given while receiving ILUMYA.
  • You have or have had any type of cancer.
  • you are pregnant, think that you may be pregnant or are planning to have a baby.
  • The effects of ILUMYA in pregnancy are unknown. It is preferable to avoid the use of ILUMYA in pregnancy.
    If you are a woman of childbearing potential, you are advised to avoid becoming pregnant and must use an effective method of contraception whilst having treatment with ILUMYA and for at least 17 weeks after treatment.
    Talk to your doctor about the benefits to you using ILUMYA verses the potential risk to your unborn child.
  • you are breast-feeding or plan to breast-feed.

If you have not told your doctor about any of the above, tell them before you start taking ILUMYA.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including:

  • any that you get without a prescription from your pharmacy, supermarket or health food shop.
  • If you have had or are due to have a vaccination. You should not receive certain types of vaccines (live vaccines) while taking ILUMYA.

How ILUMYA is given

ILUMYA may be given to you by your doctor or nurse, or you or a caregiver may be taught how to inject yourself with the medicine.

You and your doctor, nurse or pharmacist should decide if you should inject ILUMYA yourself. Do not inject yourself if you have not been properly trained by your doctor, nurse or pharmacist. A caregiver may also give you your ILUMYA injection after proper training.

How much is given

Your doctor will decide how much ILUMYA you need. The usual dose of ILUMYA is 100mg given by subcutaneous injection.

After the first dose you will need to take the same dose 4 weeks later and then all future doses once every 12 weeks.

If your doctor gives you different dosing instructions follow your doctors instructions.

Inject the whole content of the syringe.

Do not shake the syringe.

Do not exceed the recommended dose.

Injecting ILUMYA yourself

Follow all directions given to you by your doctor, nurse or pharmacist carefully, if they differ from these instructions follow your healthcare professional’s instructions.

If you do not understand the instructions, ask your doctor, nurse or pharmacist for help.

ILUMYA is intended for subcutaneous use. This means that it is injected into the fatty tissue just under the skin.

How to use the pre-filled syringe

Read all of the instructions on how to use the pre-filled syringe before beginning the injection.

Keep the instructions and refer to them as needed. These instructions will help you to inject correctly using the pre-filled syringe.

Preparation

  • For a more comfortable injection, take the carton containing the ILUMYA pre-filled syringe out of the refrigerator and let it sit at room temperature for 30 minutes before injecting.

  • Check the expiration date on the carton and pre-filled syringe and discard if the date has passed.
  • Assemble other necessary supplies, not included in the ILUMYA pack:
    - an alcohol swab,
    - a cotton ball or gauze,
    - and a sharps container or similar puncture proof container of hard plastic or glass, for syringe disposal.
  • Remove the pre-filled syringe from the carton when ready to inject.
    DO NOT pull off the needle cover until you are ready to inject.
  • Inspect ILUMYA visually and discard if it contains particles, is cloudy or discoloured, or if the syringe is damaged.
    - ILUMYA is a clear to slightly opalescent (milky) and colorless to slightly yellow, solution.
    - Air bubbles may be present; there is no need to remove them.
  • Choose an injection site with clear skin and easy access such as front of thighs, or lower abdomen, but not the area five centimetres around the navel (belly button) (Fig. 1).

If a caregiver, or healthcare professional is giving you the injection, the outer upper arms may also be used (Fig. 2).

  • DO NOT administer where the skin is tender, bruised, abnormally red, hard or affected by psoriasis.
  • DO NOT inject into scars, stretch marks, or blood vessels.

Giving the Injection

Your Doctor, Pharmacist or Nurse will give you instructions on how to inject ILUMYA subcutaneously and their instructions might differ from these instructions.

  1. When you are ready to inject, wash your hands thoroughly with soap and water.
  2. Find a clean, comfortable area to give the injection.
  3. Using a circular motion, clean the injection site with the alcohol swab. Leave to dry and do not touch the cleaned area again before injecting (Fig. 3).

  1. While holding the body of the syringe, remove the needle cover as shown and discard (Fig. 4).

  1. To inject:
a. Gently press your skin between your thumb and index finger (Fig. 5a).

b. Insert the needle in to the skin at a 45-90 degree angle (Fig. 5b).

c. Release the skin before you push on the plunger (Fig. 5c).

d. Slowly press down the blue plunger with your thumb as far as it will go (Fig. 5d). (This will activate the safety mechanism that ensures full retraction of the needle after the injection is given.)
The whole of the Dose Window will be blue when the injection is complete

e. DO NOT LET GO OF THE PLUNGER until you have removed the needle from the skin (Fig. 5e).

f. When you release the plunger the safety lock will draw the needle inside the needle guard (Fig. 5f).

g. There may be a small amount of blood at the injection site. You can press a cotton ball or gauze over the injection site and hold it for 10 seconds.

Do not rub the injection site.

You may cover the injection site with a small adhesive bandage, if needed.

  1. Dispose of the syringe in a sharps disposal container right away after use (Fig. 6).

Never try to reuse the pre-filled syringe.

How long to take ILUMYA

ILUMYA is for long term treatment. Your doctor will regularly monitor your condition to check that the treatment is having the desired effect.

Do not stop taking ILUMYA just because you feel better. It is important that you do not stop unless your doctor tells you to. It is not dangerous to stop taking ILUMYA but if you stop your psoriasis symptoms may come back.

If you use more ILUMYA than you should (overdose)

If you accidentally inject more ILUMYA than you should or you take a dose sooner than according to the doctor’s prescription, immediately telephone your doctor or the Poisons Information Centre (telephone 13 11 26) for advice, or go to Accident and Emergency at the nearest hospital.

Do this even if there are no obvious signs of discomfort or poisoning.

If you miss a dose

If you have forgotten to inject a dose of ILUMYA, inject the next dose as soon as you remember. Then talk to your doctor to discuss when you should inject the next dose.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering to take your medicine, ask your pharmacist for some hints.

While you are taking ILUMYA

Things you must do

Keep all of your doctor’s appointments so that your progress can be checked.

Look out for infections and allergic reactions

ILUMYA can potentially cause serious side effects, including infections and allergic reactions. You must look out for signs of these conditions while you are taking ILUMYA.

Stop using ILUMYA and tell your doctor or seek medical help immediately if you notice any signs indicating a possible serious infection or an allergic reaction (see Side effects).

If you need to be vaccinated, tell your doctor you are taking ILUMYA before you have the vaccination.

You should not be given a live vaccination while being treated with ILUMYA.

As soon as you start taking ILUMYA tell all doctors, dentists and pharmacists who are treating you that you are taking ILUMYA.

Remind your doctor or pharmacist you are taking ILUMYA before you start any new medicine.

Tell your doctor if you become pregnant while taking ILUMYA.

Tell your doctor or pharmacists as soon as possible if you do not feel well, you think you have an infection or you have any unwanted side effects.

Things you must not do

Never leave the pre-filled syringe lying around where others might tamper with it.

Do not use this medicine if the liquid contains easily visible particles, is cloudy or is distinctly brown.

Do not use the pre-filled syringe if any of the outer packaging is damaged, the expiry date has passed or the seals are broken.

It may not be safe for you to use.

Do not shake the pre-filled syringe.

Do not use the syringe if it is damaged or cap has been removed.

Do not take it to treat any other complaints unless your doctor tells you to.

Do not give this medicine to anyone else, even if they have the same condition as you.

Things to be careful of

Dispose of the used ILUMYA pre-filled syringe immediately after use in a sharps container.

The ILUMYA pre-filled syringe should never be re-used.

If you stop using ILUMYA

Do not stop taking your medicine or change dosage without checking with your doctor first.

Side effects

Tell your doctor, pharmacist or nurse as soon as possible if you do not feel well while taking ILUMYA.

As with all medicines, patients treated with ILUMYA may experience side effects, although not everybody gets them.

All medicines can have side effects. Sometimes they are serious, most of the time they are not.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

Some side effects are common.

  • Upper respiratory tract infections with symptoms such as sore throat and stuffy nose (nasopharyngitis)
  • Headache
  • Injection site pain

Stop using ILUMYA and tell your doctor immediately or go to hospital as you may need urgent medical attention if you have an allergic reaction.

Symptoms of an allergic reaction may include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin

Your doctor will decide if and when you may restart treatments.

Ask your doctor, nurse or pharmacist to answer any questions you may have.

Other side effects not listed above may also occur in some people. Tell your doctor if you notice anything else that is making you feel unwell.

Many medicines like ILUMYA that may decrease the activity of your immune system, may increase the risk of cancer. Tell your doctor if you notice anything unusual or if you are concerned about any aspect of your health.

After taking ILUMYA

Storage

In general:
ILUMYA pre-filled syringe should be stored in a refrigerator (between 2°C and 8°C), out of the sight and reach of children.

If required:
For purposes of travel or transporting between refrigerated storage, ILUMYA can be stored for up to 30 days at or below 25°C. After 30 days out of the refrigerator, the ILUMYA prefilled syringe should be immediately used or discarded.

Keep the product in the original carton. Protect from light until the time of use.

Do not store ILUMYA or any other medicine in the bathroom, near a sink, or leave it in the car or on a window sill.

Do not shake.

Do not freeze.

Disposal

If your doctor tells you to stop using ILUMYA or you find your pre-filled syringe has passed its expiry date, please return it to your pharmacist.

Empty pre-filled syringes should be disposed of in a sharps container or similar puncture proof container composed of hard plastic or glass.

Ask your doctor, nurse or pharmacist where you can dispose of the container once it is full.

Product description

What it looks like

ILUMYA solution for injection is a clear to slightly opalescent (milky). The colour may vary from colourless to slightly yellow solution. It is supplied in a carton pack containing 1 single use pre-filled syringe.

Ingredients

Each ILUMYA pre-filled syringe contains 100 mg tildrakizumab as the active substance.

The other ingredients are: L-histidine, L-histidine hydrochloride monohydrate, polysorbate 80, sucrose and water for injection.

This medicine does not contain lactose, gluten, tartrazine or any other azo dyes.

Sponsor

ILUMYA is supplied in Australia by:

Sun Pharma ANZ Pty Ltd
ABN 17 110 871 826
Macquarie Park Sydney NSW 2113
Telephone 1 800 726 229

Australian Registration Number: 290683

This leaflet was prepared in Sep 2024.

Published by MIMS November 2024

BRAND INFORMATION

Brand name

Ilumya

Active ingredient

Tildrakizumab

Schedule

S4

 

1 Name of Medicine

Tildrakizumab (rch).

2 Qualitative and Quantitative Composition

The single-use pre-filled syringe contains 100 mg/mL of tildrakizumab.
Tildrakizumab is a humanised IgG1/kappa monoclonal antibody produced by recombinant DNA technology in a Chinese hamster ovary (CHO) cells.
For a full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Solution for injection in a single-use pre-filled syringe.
The solution is clear to slightly opalescent and colourless to slightly yellow.

4 Clinical Particulars

4.1 Therapeutic Indications

Ilumya is indicated for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy.

4.2 Dose and Method of Administration

Ilumya is intended for use under the guidance and supervision of a physician experienced in the diagnosis and treatment of psoriasis. It is administered by subcutaneous injection.

Dosage.

Adults.

The recommended dose of Ilumya is 100 mg by subcutaneous injection at weeks 0, 4 and every 12 weeks thereafter.
If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regularly scheduled interval.

Method of administration.

Ilumya (1 mL) is administered by subcutaneous injection. Full instructions for use are provided in the Consumer Medicine Information.
After proper training in subcutaneous injection technique, patients may self-inject Ilumya if a healthcare professional determines that it is appropriate. However, the physician should ensure appropriate follow-up of patients.
Sites for injection include abdomen, thighs, or upper arm. Do not administer 5 cm around the navel or where the skin is tender, bruised, abnormally red, indurated or affected by psoriasis. Do not inject into scars, stretch marks, or blood vessels.
The pre-filled syringe should be visually inspected for particulate matter and discolouration prior to administration. Product exhibiting particulate matter or discolouration must not be used. Do not shake.
Ilumya does not contain any antimicrobial preservatives. Discard any unused product remaining in the pre-filled syringe. Ilumya pre-filled syringes are for single-use in one patient only.

Dosage adjustments.

Renal or hepatic impairment.

Ilumya has not been studied in these patient populations. No dose recommendations can be made.

Elderly (≥ 65 years).

No dose adjustment is required (see Section 5.2 Pharmacokinetic Properties).

Paediatric population.

The safety and efficacy of Ilumya in children and adolescents under 18 years of age has not yet been evaluated.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients (see Section 4.4 Special Warnings and Precautions for Use; Section 6.1 List of Excipients).
Clinically important active infection (e.g. active tuberculosis, see Section 4.4 Special Warnings and Precautions for Use).

4.4 Special Warnings and Precautions for Use

Infections.

In clinical trials, there was no increased risk of infection in subjects treated with Ilumya, however patients with active infections or a history of recurrent infections were not included in clinical trials. Caution should be exercised when considering the use of Ilumya in patients with a chronic infection or a history of recurrent infection. If a patient develops a serious infection whilst on treatment with Ilumya, the patient should be closely monitored.
Ilumya must not be given to patients with active tuberculosis (TB).

Pre-treatment evaluation for tuberculosis.

Prior to initiating treatment with Ilumya, patients should be evaluated for tuberculosis (TB) infection. Patients receiving Ilumya should be monitored for signs and symptoms of active TB during and after treatment. Anti-TB therapy should be considered prior to initiating Ilumya in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed.

Hypersensitivity.

Non-serious cases of urticaria occurred in Ilumya-treated subjects in clinical trials. If a serious hypersensitivity reaction occurs, administration of Ilumya should be discontinued immediately and appropriate therapy initiated.

Immunisations.

Prior to initiating treatment with Ilumya, consider completion of all appropriate immunisations according to current immunisation guidelines. If a patient has received live viral or bacterial vaccination it is recommended to wait at least 4 weeks prior to starting treatment with tildrakizumab. Patients treated with Ilumya should not receive live vaccines during treatment and for at least 17 weeks after treatment (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Malignancy.

In the initial placebo-controlled period of the Phase 2 and Phase 3 studies, a non-significant numerical imbalance between tildrakizumab-treated patients and those receiving placebo with malignancies was reported (see Section 4.8 Adverse Effects (Undesirable Effects)). As patients with prior or concurrent malignancy were excluded from the clinical trials, caution should be observed when treating patients with a history of malignancy or those who develop a malignancy during therapy.

Use in the elderly.

See Section 5.2 Pharmacokinetic Properties.

Paediatric use.

The safety and efficacy of Ilumya in children and adolescents under 18 years of age has not yet been evaluated.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Live vaccines should not be given concurrently with Ilumya (see Section 4.4 Special Warnings and Precautions for Use).
Results from a drug-drug interactions study conducted in psoriasis subjects suggest that Ilumya had no clinically relevant effect on cytochrome p450 (CYP) enzymes CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 (see Section 5.2 Pharmacokinetic Properties, Drug interactions).
The safety of Ilumya in combination with other immunomodulatory agents or phototherapy has not been evaluated.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

The effect of Ilumya on human fertility has not been evaluated.
The effects of tildrakizumab were not directly assessed in dedicated animal fertility studies. However, no effects on fertility parameters such as reproductive organs, menstrual cycle length, and/or hormones were observed in male and female cynomolgus monkeys that were administered tildrakizumab at up to 100 mg/kg by subcutaneous injections once every 14 days (> 100 times the human exposure at the recommended dose based on AUC) for 9 months.
(Category B1)
There is limited information regarding the use of Ilumya in pregnant women. As a precautionary measure, it is preferable to avoid the use of Ilumya during pregnancy. Women of childbearing potential should use an effective method of contraception during treatment and for at least 17 weeks after treatment.
Animal studies do not indicate direct or indirect harmful effect with respect to pregnancy, embryonic/fetal development, parturition or post-natal development. In a pre- and postnatal development toxicity study in monkeys given up to 100 mg/kg tildrakizumab by subcutaneous injections once every 14 days (> 100 times the human exposure at the recommended dose), no related increase in pregnancy loss was observed.
Tildrakizumab was shown to distribute across the placental barrier. After repeated dosing to pregnant cynomolgus monkeys, serum concentrations were quantifiable in the fetus however the reproduction toxicity studies did not reveal any untoward effects. No harmful effects were noted in neonates at maternal exposures up to 19 times the human exposure at the recommended dose. Two neonatal deaths from monkeys administered tildrakizumab at maternal exposure of > 100 times the human exposure at the recommended dose were attributed to possible viral infection and considered of uncertain relationship to the treatment. The clinical significance of these findings is unknown.
 It is not known whether tildrakizumab is excreted in human milk. In a pre-/postnatal development study tildrakizumab was detected at low levels in breast milk in monkeys dosed with tildrakizumab from gestation day 50 to parturition. The milk/serum ratio was ≤ 0.002. In the same study, serum levels of tildrakizumab in infants up to 91 days old were similar to, or exceed maternal serum levels.
A decision should be made whether to discontinue breast-feeding or to discontinue Ilumya taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

4.7 Effects on Ability to Drive and Use Machines

Ilumya has no or negligible influence on the ability to drive and use machines.

4.8 Adverse Effects (Undesirable Effects)

The most common adverse reactions observed with Ilumya in the pooled data from one Phase 2 and two Phase 3 studies in psoriasis patients for the placebo controlled period (16 weeks for the Phase 2 study and 12 weeks for the Phase 3 studies) were nasopharyngitis, headache, and site injection pain.
Most adverse reactions were considered mild and no adverse reaction led to discontinuation of treatment in > 1% of patients. For clinical management of specific adverse reactions, see Section 4.4 Special Warnings and Precautions for Use.
The frequency of adverse reactions is defined using the following convention: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); and not known (cannot be estimated from available data).
Table 1 provides a summary of the adverse reactions that were reported at a frequency of > 1% and at a higher rate in the Ilumya group than in the placebo group.

Immunogenicity.

In the Phase 2 and Phase 3 psoriasis clinical studies 6.5% of patients treated continuously with Ilumya 100 mg developed antibodies to Ilumya. In the subset of these patients with treatment emergent neutralising antibodies, a small decrease in serum tildrakizumab concentrations and a corresponding increase in clearance was observed. Those patients who developed neutralising antibodies reported minor decreases in some efficacy parameters. No apparent association between the development of antibodies to Ilumya and the development of treatment emergent adverse events was seen.

Hypersensitivity reactions.

Non-serious cases of urticaria occurred in Ilumya-treated subjects in clinical trials. If a serious hypersensitivity reaction occurs, administration of Ilumya should be discontinued immediately and appropriate therapy initiated. See Section 4.4 Special Warnings and Precautions for Use, Hypersensitivity.

Malignancy.

In the initial placebo-controlled period of the Phase 2 and Phase 3 studies, a non-significant numerical imbalance in malignancy was reported between tildrakizumab-treated patients (0.2%) and those receiving placebo (0.0%). This imbalance was not observed in the controlled-data period (exposure-adjusted incidence rate of 1.2/100 patient years of exposure for tildrakizumab 100 mg, 1.7/100 patient years 200 mg, 2.6/100 patient years with etanercept, 0.9/100 patient years with placebo) or in the data collected in the open label extensions to the pivotal studies following up to 5 years of treatment (exposure adjusted rates of 0.7/100 patient with tildrakizumab 100 mg and 0.8/100 patient years with tildrakizumab 200 mg). The overall rate of malignancies reported with tildrakizumab across all studies was 0.422/100 patient years exposure (excluding non-melanoma skin cancer (NMSC)) and 0.348/100 patient years for non-melanoma skin cancer.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at http://www.tga.gov.au/reporting-problems.

4.9 Overdose

Intravenous doses up to 10 mg/kg have been safely administered in clinical trials.
In the event of overdose, it is recommended that the patient be monitored for any signs or symptoms of adverse reactions and appropriate symptomatic treatment be instituted immediately.
For information on the management of overdose, contact the Poison Information Centre on 131 126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

The expression of mRNA for IL-23p19 is elevated in psoriatic lesions compared to normal skin. In exploratory studies in patients with psoriasis, inflammatory infiltrates were decreased in lesional tissue biopsies after dosing with tildrakizumab. A decrease in expression of IL-23p19 was observed in lesional skin biopsies measured at baseline and up to two weeks post-treatment. Gene expression patterns of inflammation were normalised following treatment with tildrakizumab.

Mechanism of action.

Tildrakizumab is a humanized IgG1/kappa monoclonal antibody that specifically binds to the p19 protein subunit of the interleukin 23 (IL-23) cytokine and inhibits its interaction with the IL-23 receptor.
IL-23 is a naturally occurring cytokine composed of 2 subunits (IL-23p19 and IL-12/23p40), that is involved in inflammatory and immune responses. Tildrakizumab inhibits the release of proinflammatory cytokines and chemokines. In in vitro models, tildrakizumab was shown to disrupt IL-23 mediated signalling and cytokine cascades by disrupting the interaction of IL-23 binding to its specific receptor, IL-23R without binding to IL-12 (composed of 2 subunits IL-12p35 and IL-12/23p40).

Clinical trials.

The multicenter, randomized, double-blind, placebo-controlled trials reSURFACE 1 and reSURFACE 2 enrolled a total of 1862 patients 18 years of age and older with plaque psoriasis who had a minimum body surface area involvement of 10%, a Physician Global Assessment (PGA) score of ≥ 3 in the overall assessment (plaque thickness, 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 these studies, there was an initial 12 week placebo controlled period where patients were randomized to Ilumya (including 100 mg and 200 mg at 0, 4 and every twelve weeks thereafter [Q12W]) or placebo. In the active comparator study (reSURFACE 2), patients were also randomized to receive etanercept 50 mg twice weekly for 12 weeks, and weekly thereafter up to 28 weeks. After the initial 12 week treatment period, patients previously receiving placebo were randomized to either 100 mg or 200 mg Ilumya through week 28. After week 28, those patients receiving Ilumya from week 0 were eligible for dosage adjustment based on PASI response. In reSURFACE 2, non-responding or partial-responding patients receiving etanercept were switched to Ilumya 200 mg. The total treatment period was 52 or 64 weeks for the base studies, each study also incorporated an optional long-term extension phase.
Results obtained at Weeks 12, 28 and beyond (up to Week 64 in reSURFACE 1 and up to Week 52 in reSURFACE 2) are presented in Table 2.
Patients in all treatment groups (reSURFACE 1 and re SURFACE 2) had a median baseline PASI score ranging from 17.6 to 18.4. The baseline PGA score was marked or severe in 33.4% of patients. Of all patients enrolled, 35.8% had received prior phototherapy, 41.1% had received prior conventional systemic therapy, 16.7% had received prior biologic therapy for the treatment of psoriasis, and 7.7% had received at least one anti-TNF alpha agent. A total of 15.4% of study patients had a history of psoriatic arthritis. Baseline Dermatology Life Quality Index (DLQI) ranged from 13.2 to 14.8.
Studies reSURFACE 1 and reSURFACE 2 assessed the changes from baseline at Week 12 in the two co-primary endpoints: 1) PASI 75 and 2) PGA of "0" (cleared) or "1" (minimal), with at least a 2-point improvement from baseline. Other evaluated outcomes in reSURFACE 1 and reSURFACE 2 included the proportion of patients who achieved PASI 90 and PASI 100, the proportion of patients with DLQI 0 or 1, and maintenance of efficacy up to 64 weeks.
Examination of age, race, previous treatment with a biologic or traditional systemic therapy did not identify significant differences in PASI 75 response to Ilumya 100 mg among these subgroups at Week 12.
Maintenance of response. To evaluate the maintenance and durability of response, patients originally randomized to Ilumya who were responders at Week 28 (i.e. had achieved PASI 75 response) in reSURFACE 1 were re-randomized to an additional 36 weeks of either maintaining the same dose of Ilumya Q12W (every twelve weeks) or placebo.
Of the patients continuing with the same dose of Ilumya, 87.5% of patients treated with Ilumya 100 mg maintained PASI 75 response at week 64. Of the patients re-randomized to receive placebo, 49% of patients originally treated with 100 mg tildrakizumab maintained PASI 75 response at Week 64.
Retreatment after relapse. In patients re-randomized to placebo in reSURFACE 1, 54.4% (who were originally treated with 100 mg) experienced relapse (defined as a reduction in maximum PASI response by 50%). These patients were restarted on their original dose of Ilumya upon relapse. After a minimum of 12 weeks from re-initiation of therapy, over 85% had regained a PASI 75 response by Week 64.
Quality of life/patient-reported outcomes. At Week 12 and across studies, Ilumya was associated with statistically significant improvement in Health-related Quality of Life as assessed by the Dermatology Life Quality Index (DLQI). The proportion of patients treated with Ilumya who achieved DLQI 0 or 1 at W12 was 41% and 40%, in reSURFACE 1 and 2 respectively. Improvements were maintained over a year with DLQI 0/1 achieved by 64% and 69% of patients treated with 100 mg in reSURFACE 1 and 2 respectively. At Week 52, 82% (reSURFACE 1) and 87% (reSURFACE 2) of the patients on Ilumya 100 mg had a DLQI score < 5 points.
In reSURFACE 1, the physical and mental component summary scores of the Short Form Health Survey (SF-36) were significantly improved in patients treated with Ilumya compared with placebo.
Treatment maintenance in partial responders. 68.4% patients (reSURFACE 2) originally randomized to Ilumya 100 mg who achieved a PASI response of ≥ 50% but < 75% improvement from Baseline at Week 28 (3 doses) and remained on Ilumya 100 mg (n ~ 20), achieved a PASI 75 response at Week 52 (i.e. 3 additional doses).
Psoriasis of the scalp. In a multicenter, randomized, double-blind, placebo-controlled trial (Trial [NCT03897088]) 231 subjects with moderate to severe psoriasis of the scalp were treated with Ilumya 100 mg (n=117) or placebo (n=114) at Week 0 and 4 and every 12 weeks thereafter. Of the 231 randomized subjects, 217 subjects completed Part 1 (Day 1 to Week 16). For Week 16 to Week 52, subjects randomized to placebo were switched to Ilumya receiving 100 mg at Weeks 16, 20, 32, and 44. Those in the Tildrakizumab 100 mg arm continued to receive Tildrakizumab 100 mg at Weeks 16, 28, 40, and 52. After Week 52, the study treatments were stopped, and all subjects entered the 20-week observational treatment-free safety follow-up period to monitor safety and tolerability following the last dose of treatment.
The primary endpoint was the proportion of subjects with IGA score for the scalp of "clear" and "almost clear" with at least 2-point reduction from Baseline at Week 16.
Other evaluated outcomes included the proportion of subjects achieving a) Psoriasis Scalp Severity Index (PSSI) 90 (≥ 90% improvement from Baseline in PSSI) at Week 16; b) subjects achieving PSSI 90 at Week 12; and c) IGA for the scalp score of "clear" or "almost clear" with at a least a 2-point reduction from Baseline at Week 12.
Subjects in the Ilumya and placebo treatment groups were predominantly men (60.2%) and White (78.9), with a mean age of 44.8 years. At baseline, these subjects had a median affected scalp surface area (SSA) of 50%, a median PASI score of 16.7, and PGA score of 3 ("moderate") or 4 ("severe") in 87.1% and 12.3%, respectively.

Clinical response in trial.

The results from trial are presented in Table 3.
Both the groups were assessed for safety; no new safety signals were identified.

5.2 Pharmacokinetic Properties

Absorption.

The subcutaneous formulation of tildrakizumab was characterized with an absolute bioavailability of 73-90% and slow absorption with time to reach maximum concentration at 6.2 days after injection. Steady-state was achieved by 16 weeks with the clinical regimen of 0, 4, and every 12 weeks thereafter, with 1.1-fold accumulation in exposure between Week-1 and Week-12 independent of dose.
At steady state, following administration of 100 mg of tildrakizumab in subjects with moderate to severe psoriasis geometric means (% CV) of AUC0-T and Cmax values were 305 microgram*day/mL (41%) and 8.1 microgram/mL (34%), respectively.
Tildrakizumab pharmacokinetics exhibited low to moderate variability (33-41%).

Distribution.

Tildrakizumab has limited extravascular distribution with volume of distribution (Vd) values ranging from 76.9 to 106 mL/kg.

Metabolism.

Tildrakizumab is catabolized into component amino acids by general protein degradation processes.
Small-molecule metabolic pathways (e.g. cytochrome P450 enzymes (CYPs), glucuronosyltransferases) do not contribute to its clearance.

Excretion.

The geometric mean systemic clearance (CV %) was 0.32 L/day (38%) and the half-life was 23.4 days (23%) in subjects with plaque psoriasis.

Dose linearity.

Tildrakizumab exhibited dose-proportional pharmacokinetics in subjects with plaque psoriasis over a dose range from 50 mg to 200 mg, and in healthy subjects at doses from 50 mg to 400 mg following subcutaneous administration, with clearance being independent of dose.

Special populations.

Elderly.

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

Renal and hepatic impairment.

No formal trial on the effect of hepatic or renal impairment on the pharmacokinetics of tildrakizumab has been conducted.

Drug interactions.

A clinical pharmacology study, administering 200 mg of tildrakizumab subcutaneously on Day 1 and Day 29 demonstrated that tildrakizumab does not have a clinically relevant effect on the pharmacokinetics of caffeine (CYP1A2 probe substrate), warfarin (CYP2C9 probe substrate), omeprazole (2C19 probe substrate), dextromethorphan (CYP2D6 probe substrate) or midazolam (CYP3A4 probe substrate). (See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.)

5.3 Preclinical Safety Data

Genotoxicity.

Ilumya has not been evaluated for genotoxic potential.

Carcinogenicity.

Animal carcinogenicity studies have not been conducted with tildrakizumab. Studies in mouse tumour models showed that selective inhibition of IL-23p19 does not increase carcinogenic risk.

6 Pharmaceutical Particulars

6.1 List of Excipients

Histidine, histidine hydrochloride monohydrate, polysorbate 80, sucrose and water for injections.

6.2 Incompatibilities

Not known.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store at 2°C to 8°C. Refrigerate. Do not freeze.
Ilumya is stable for up to 30 days at 25°C.
Protect from light. Keep the pre-filled syringe in the outer carton until ready to use. Do not shake.

6.5 Nature and Contents of Container

Ilumya solution for injection is supplied as a single-use, pre-filled syringe comprising a clear glass barrel with a stainless-steel needle, latex-free rubber plunger stopper and needle shield. Each pre-filled syringe is assembled with a needle safety device for subcutaneous (sc) administration.
Pack size of 1 pre-filled syringe.

6.6 Special Precautions for Disposal

No special requirements for disposal.
In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Ilumya (tildrakizumab) is a humanised IgG1/kappa monoclonal antibody produced by recombinant DNA technology in a Chinese hamster ovary (CHO) cells. It is composed of two identical heavy chains of 446 amino acids each and two identical light chains of 214 amino acids each linked by interchain disulfide bonds, with an approximate molecular weight of 147.0 kDa.

Chemical structure.


CAS number.

CAS Registry No: 1326244-10-3.

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription Only Medicine.

Summary Table of Changes