Consumer medicine information

Bimzelx

Bimekizumab

BRAND INFORMATION

Brand name

Bimzelx

Active ingredient

Bimekizumab

Schedule

SUMMARY CMI

Bimzelx^®

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

▼ This medicine is new or being used differently. Please report side effects. See the full CMI for further details.

1. Why am I using Bimzelx^®?

Bimzelx^® contains the active ingredient bimekizumab. Bimzelx^® is used to treat adult patients with plaque psoriasis, psoriatic arthritis, ankylosing spondylitis and non‐radiographic axial spondyloarthritis.

For more information, see Section 1. Why am I using Bimzelx^®? in the full CMI.

2. What should I know before I use Bimzelx^®?

Do not use if you have ever had an allergic reaction to Bimzelx^® or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use Bimzelx^®? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Bimzelx^® and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use Bimzelx^®?

Your healthcare professional should show you how to prepare and inject Bimzelx^® using the pre‐filled syringe or pen. Do not inject yourself or someone else until you have been shown how to inject Bimzelx^® the right way.
You and your caregiver should read Section 4. How do I use Bimzelx^®? before each use of Bimzelx^®.
Depending on your prescribed dose, you will need 1 or 2 Bimzelx^® pre‐filled syringe(s) or pen(s) to receive your full dose

More instructions can be found in Section 4. How do I use Bimzelx^®? in the full CMI.

5. What should I know while using Bimzelx^®?

Things you should do	Remind any doctor, dentist or pharmacist you visit that you are using Bimzelx^®. Use the product once in one patient only and discard any residue after use.
Things you should not do	Do not stop using Bimzelx or change the dose unless your doctor tells you to. Do not inject yourself with this medicine unless you have been trained by a healthcare professional. Do not use this medicine after the expiry date which is stated on the label and carton after EXP.
Looking after your medicine	Keep this medicine out of the sight and reach of children. Store in a refrigerator between 2°C – 8°C. Do not freeze. Keep in the outer carton to protect from light. Bimzelx^® may be stored at room temperature (up to 25°C) for a single period of maximum 30 days with protection from light. Once removed from the refrigerator and stored under these conditions, discard after 30 days or by the expiry date, whichever occurs first.

For more information, see Section 5. What should I know while using Bimzelx^®? in the full CMI.

6. Are there any side effects?

Common side effects include: Upper respiratory tract infections (sore throat and stuffy nose), thrush in mouth or throat, athlete's foot, cold sores, gastroenteritis (symptoms may include diarrhoea; nausea; vomiting; stomach pain; indigestion; decrease in appetite), inflamed hair follicles, headache, acne, redness, pain or swelling at the site of injection and feeling tired.

Serious side effects include: Serious infections ‐ symptoms may include fever, flu like symptoms, night sweats, feeling tired or short of breath, cough which will not go away, warm, red and painful skin or a painful rash with blisters

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

▼ This medicine is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. You can report side effects to your doctor, or directly at www.tga.gov.au/reporting-problems.

FULL CMI

Bimzelx^®

Active ingredient(s): bimekizumab

Consumer Medicine Information (CMI)

This leaflet provides important information about using Bimzelx^®. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using Bimzelx^®.

Where to find information in this leaflet:

1. Why am I using Bimzelx^®?
2. What should I know before I use Bimzelx^®?
3. What if I am taking other medicines?
4. How do I use Bimzelx^®?
5. What should I know while using Bimzelx^®?
6. Are there any side effects?
7. Product details

1. Why am I using Bimzelx^®?

Bimzelx^® contains the active ingredient bimekizumab.
Bimzelx^® belongs to a group of medicines called interleukin (IL) inhibitors. Bimekizumab works by reducing the activity of two proteins called IL‐17A and IL‐17F. There are higher levels of these proteins in diseases such as psoriasis.

Bimzelx^® is used to treat the following inflammatory diseases in adults:

plaque psoriasis (red, itchy and inflamed skin)

psoriatic arthritis (joint pain, tenderness, swelling and stiffness and similar symptoms to plaque psoriasis)

ankylosing spondylitis and non‐radiographic axial spondyloarthritis (back pain and morning stiffness)

2. What should I know before I use Bimzelx^®?

Warnings

Do not use Bimzelx^® if:

you are allergic to bimekizumab, or any of the ingredients listed at the end of this leaflet.
Always check the ingredients to make sure you can use this medicine.

Check with your doctor if you:

have any other medical conditions such as ongoing infections or an infection that keeps coming back or tuberculosis.
have inflammatory bowel disease.
take any medicines for any other condition.
recently had or plan to have a vaccination. You should not be given certain types of vaccines, such as live vaccines while using Bimzelx^®.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

Bimzelx^® should be used in pregnancy only if the benefits clearly outweigh the potential risks.

Children and adolescents

Bimzelx^® is not recommended for children and young people under 18 years of age. This is because it has not been studied in this age group.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect Bimzelx^®.

4. How do I use Bimzelx^®?

How much to use

The recommended dose, given as injections under your skin is as follows:
Plaque Psoriasis:
- 320 mg (given as two pre‐filled syringes or pens, containing 160 mg each) at Weeks 0, 4, 8, 12, 16.
- From Week 16, you will use 320 mg given as two pre‐filled syringes or pens, containing 160 mg each) every 8 weeks. If you weigh more than 120 kg, your doctor may decide to continue every 4 weeks from Week 16
Psoriatic Arthritis, Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis:
- 160 mg (given as one pre‐filled syringe or pen) every 4 weeks.
- If you have psoriatic arthritis and plaque psoriasis, your doctor may decide to prescribe you the same dose outlined for plaque psoriasis.
Your healthcare professional should show you how to prepare and inject Bimzelx^® using the pre‐filled syringe or pen. Do not inject yourself or someone else until you have been shown how to inject Bimzelx^® the right way.
You and your caregiver should read 4. How do I use Bimzelx^®? before each use of Bimzelx^®.
Depending on your prescribed dose, you will need 1 or 2 Bimzelx^® pre‐filled syringe(s) or pen(s) to receive your full dose.
Tell your doctor before you stop using Bimzelx.

When to use Bimzelx^®

Bimzelx^® should be used as instructed by your doctor.

How to Inject Bimzelx^® pre‐filled syringe

Bimzelx^® pre‐filled syringe at a glance (see figure A):

The Bimzelx^® pre‐filled syringe has a needle safety feature. This will cover the needle automatically after the injection is finished. The needle safety feature will help to prevent the needle sticking into anyone who handles the pre‐filled syringe after injection.

For a more comfortable injection: Take the Bimzelx^® prefilled syringe(s) carton(s) out of the refrigerator and let it (them) sit on a flat surface at room temperature for 30 to 45 minutes before injecting.

Do not warm in any other way, such as in a microwave or in hot water.
Do not shake the pre‐filled syringe(s).
Do not uncap the pre‐filled syringe(s) until you are ready to inject.

Step 1: Setting up for your injection(s)

Depending on your prescribed dose, place the following items on a clean, flat, well‐lit work surface, like a table:

1 or 2 Bimzelx^® pre‐filled syringe(s)

You will also need (not included in the carton):

1 or 2 alcohol wipes
1 or 2 clean cotton balls
1 sharps disposal container.

Step 2: Choose injection site and prepare your injection

2a: Choose your injection site

The places you may chose for your injection are:
- your stomach (abdomen) or your thigh (see Figure B).
- the back of your arm may also be used if a caregiver is giving you the injection (see Figure C).

Do not inject into areas where the skin is tender, bruised, red, scaly, hard or areas with scars or stretch marks.
Do not inject within 5cm of the belly‐button (navel).
If a second injection is needed for your prescribed dose (320mg), you should use a different place for your second injection. Do not use the same place to inject twice in a row.

2b: Wash your hands well with soap and water and dry with a clean towel

2c: Prepare your skin

Clean the injection site with an alcohol wipe. Let the area dry completely. Do not touch the cleaned area again before injecting.

2d: Check the pre‐filled syringe (see Figure D)

Make sure the name Bimzelx^® and expiry date appear on the label.
Check the medicine through the viewing window. The medicine inside should be clear to slightly opalescent and free of particles. Its colour may vary from colourless to pale brownish‐yellow. You may see air bubbles in the liquid. This is normal.
Do not use the Bimzelx^® pre‐filled syringe if the medicine is cloudy, discoloured, or has particles.

Step 3: Inject Bimzelx^®

3a: Remove the pre‐filled syringe needle cap

Hold the pre‐filled syringe around the finger grip with one hand. Pull the cap straight off the pre‐filled syringe with the other hand (see Figure E). You may see a drop of liquid on the tip of the needle, this is normal.

Do not touch the needle or let the needle touch any surface.
Do not hold the plunger rod when you remove the cap. If you accidentally remove the plunger rod, throw the pre‐filled syringe in the sharps disposal container and get a new one.
Do not put the needle cap back on. If you do, you could damage the needle or prick yourself by accident.

3b: Gently pinch and hold with one hand a fold of skin that you cleaned for the injection. With the other hand, insert the needle into your skin at about 45 degree angle

Push the needle all the way in. Then gently let go of your skin. Make sure the needle is in place (see Figure F).

3c: Firmly push the plunger head all the way down until all the medicine is injected (see Figure G)

All the medicine is injected when you cannot push the plunger head any further (see Figure H).

3d: Lift your thumb off the plunger head (see Figure I). The needle will automatically move back in and lock in place

Press a dry cotton ball over the injection site for a few seconds. Do not rub the injection site. You may see slight bleeding or a drop of liquid. This is normal. You may cover the injection site with a small adhesive bandage, if needed.

Step 4: Throw away the used Bimzelx^® pre‐filled syringe

Put the used pre‐filled syringe in a sharps disposal container straight away after use (see Figure J).

If you need to have a second injection as prescribed by your doctor, use a new Bimzelx^® pre‐filled syringe and repeat steps 2 to 4.

Make sure to select a new injection site for your second injection.

How to Inject Bimzelx^® pre‐filled pen

Bimzelx^® pre‐filled pen at a glance (see figure A):

For a more comfortable injection: Take the Bimzelx^® pre-filled pen(s) carton(s) out of the refrigerator and let it (them) sit on a flat surface at room temperature for 30 to 45 minutes before injecting.

Do not warm in any other way, such as in a microwave or in hot water.
Do not shake the pre‐filled pen(s).
Do not uncap the pre‐filled pen(s) until you are ready to inject.

Step 1: Setting up for your injection(s)

Depending on your prescribed dose, place the following items on a clean, flat, well‐lit work surface, like a table:

1 or 2 Bimzelx^® pre‐filled pen(s)

You will also need (not included in the carton):

1 or 2 alcohol wipes
1 or 2 clean cotton balls
1 sharps disposal container.

Step 2: Choose injection site and prepare your injection

2a: Choose your injection site

The places you may chose for your injection are:
- your stomach (abdomen) or your thigh (see Figure B).
- the back of your arm may also be used if a caregiver is giving you the injection (see Figure C).

Do not inject into areas where the skin is tender, bruised, red, scaly, hard or areas with scars or stretch marks.
Do not inject within 5cm of the belly‐button (navel).
If a second injection is needed for your prescribed dose (320mg), you should use a different place for your second injection. Do not use the same place to inject twice in a row.

2b: Wash your hands well with soap and water and dry with a clean towel

2c: Prepare your skin

Clean the injection site with an alcohol wipe. Let the area dry completely. Do not touch the cleaned area again before injecting.

2d: Check the pre‐filled pen (see Figure D)

Make sure the name Bimzelx^® and expiry date appear on the label.
Check the medicine through the viewing window. The medicine inside should be clear to slightly opalescent and free of particles. Its colour may vary from colourless to pale brownish‐yellow. You may see air bubbles in the liquid. This is normal.
Do not use the Bimzelx^® pre‐filled pen if the medicine is cloudy, discoloured, or has particles.

Step 3: Inject Bimzelx^®

3a: Remove the pre‐filled pen cap

Hold the pre‐filled pen firmly with one hand around the handle. Pull the cap straight off the pre‐filled pen with the other hand (see Figure E). Although you cannot see the needle tip, it is now uncovered.
Do not touch the needle guard or put the cap back on. This is because it could activate the pre‐filled pen and you could prick yourself.

3b: Hold the pre‐filled pen at a 90 degree angle to the cleaned injection site (see Figure F)

3c: Place the pre‐filled pen flat against your skin, then firmly press the pre‐filled pen down against your skin

You will hear a click sound. Your injection begins when the first “click” is heard (see Figure G). Do not lift the pre‐filled pen away from the skin.

3d: Keep holding the pre‐filled pen in place and pressed firmly against your skin

You will hear a second “click” within 15 seconds after you hear the first click.
The second click tells you that all the medicine has been injected and your Bimzelx^® injection is finished. You should see the yellow colour indicator filling the viewing window (see Figure H).

3e: Remove the pre‐filled pen by carefully pulling it straight up from your skin. The needle guard will automatically cover the needle

Press a dry cotton ball over the injection site for a few seconds. Do not rub the injection site. You may see slight bleeding or drop of liquid. This is normal. You may cover the injection site with a small adhesive bandage, if needed.

Step 4: Throw away the used Bimzelx^® pre‐filled pen

Put the used pre‐filled pen in a sharps disposal container straight away after use (see Figure I).

If you need to have a second injection as prescribed by your doctor, use a new Bimzelx^® pre‐filled pen and repeat steps 2 to 4.

Make sure to select a new injection site for your second injection.

If you forget to use Bimzelx^®

If you miss your Bimzelx^® dose, inject a dose as soon as you remember. Then, take your next dose at your regular scheduled time. Call your doctor if you are not sure what to do.

Do not take a double dose to make up for the dose you missed.

If you use too much Bimzelx^®

If you think that you have used too much Bimzelx^®, you may need urgent medical attention.

You should immediately:

phone the Poisons Information Centre
(by calling 13 11 26), or
contact your doctor, or
go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using Bimzelx^®?

Things you should do

Remind any doctor, dentist or pharmacist you visit that you are using Bimzelx^®.
Use the product once in one patient only and discard any residue after use.

Call your doctor straight away if you:

have an infection or an infection that keeps coming back.
plan to have a vaccination. You should not get certain types of vaccines, such as live vaccines while using Bimzelx^®.
start to experience new symptoms or worsening of your existing symptoms of an inflammatory bowel disease.

Things you should not do

Do not stop using Bimzelx^® or change the dose unless your doctor tells you to.
Do not inject yourself with this medicine unless you have been trained by a healthcare professional.
Do not use this medicine after the expiry date which is stated on the label and carton after EXP.
Do not use this medicine if the carton seal is broken.
Do not use this medicine if the pre‐filled syringe/pen has been dropped or looks damaged.
Do not use this medicine if the liquid has ever been frozen (even if thawed).

Driving or using machines

Be careful before you drive or use any machines or tools until you know how Bimzelx^® affects you.

Bimzelx^® is not anticipated to have any influence on the ability to drive and use machines.

Looking after your medicine

Store in a refrigerator between 2°C – 8°C.
Do not freeze.
Keep the pre‐filled syringe or pen in the outer carton in order to protect from light.
The Bimzelx^® pre‐filled syringe and pre‐filled pen may be stored at room temperature (up to 25°C) for a single period of maximum 30 days with protection from light. Once removed from the refrigerator and stored under these conditions, discard after 30 days or by the expiry date, whichever occurs first. A field for the date is provided on the carton to record the date removed from the refrigerator.

Follow the instructions in the carton on how to take care of your medicine properly.

Keep it where young children cannot reach it.

When to discard your medicine (as relevant)

Discard after the expiry date, or 30 days after removed from the refrigerator.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effects

What to do

Infection:

upper respiratory infections with symptoms such as sore throat and stuffy nose
cold sores
thrush in mouth, throat or vagina
inflamed hair follicles
acne
athlete's foot
urinary tract infection
eye infection

Injection site reactions:

redness, pain or swelling at the site of injection

Stomach and gut:

gastroenteritis (symptoms may include diarrhoea, nausea, vomiting, stomach pain, indigestion, decrease in appetite)

General:

headache
feeling tired
dry skin
changes in some blood tests such as liver function tests

Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effects

What to do

Serious infections, symptoms may include:

fever, flu‐like symptoms, night sweats
feeling tired or short of breath, cough which will not go away
warm, red and painful skin, or a painful skin rash with blisters

Allergic reaction:

difficulty breathing or swallowing
low blood pressure, which can make you dizzy or light‐headed
swelling of the face, lips, tongue or throat
severe itching of the skin, with a red rash or raised bumps.

Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What Bimzelx^® contains

Active ingredient (main ingredient)	Bimekizumab
Other ingredients (inactive ingredients)	glycine, sodium acetate trihydrate, acetic acid, polysorbate 80 and water for injections

Do not take this medicine if you are allergic to any of these ingredients.

What Bimzelx^® looks like

Bimzelx^® is a clear to slightly opalescent and pale brownish‐yellow liquid. It comes in a single use disposable pre‐filled syringe or pen.

Bimzelx^® is available in unit packs containing 2 pre‐filled syringes/pens. (AUST R 353269/353268).

Who distributes Bimzelx^®

UCB Pharma
A division of UCB Australia Pty Ltd
Level 1, 1155 Malvern Road
Malvern VIC 3144, Australia
Phone: +613 9828 1800
Website: www.ucbaustralia.com.au
E‐mail: [email protected]

This leaflet was prepared in April 2024

Published by MIMS June 2024

BRAND INFORMATION

Brand name

Bimzelx

Active ingredient

Bimekizumab

Schedule

1 Name of Medicine

Bimekizumab.

2 Qualitative and Quantitative Composition

Each pre-filled syringe or pen contains 160 mg bimekizumab in 1 mL.
Bimekizumab is a recombinant humanized full-length monoclonal antibody of the IgG1 sub-class, expressed in a genetically engineered Chinese hamster ovary cell line.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Solution for injection.
The solution is clear to slightly opalescent and colourless to pale brownish-yellow.

4 Clinical Particulars

4.1 Therapeutic Indications

Plaque psoriasis.

Bimzelx is indicated for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy.

Psoriatic arthritis.

Bimzelx is indicated for the treatment of adult patients with active psoriatic arthritis who have had an inadequate response to or who have been intolerant to previous disease modifying antirheumatic drug (DMARD) therapy.

Axial spondyloarthritis.

Non-radiographic axial spondyloarthritis (nr-axSpA).

Bimzelx is indicated for the treatment of adult patients with active non-radiographic axial spondyloarthritis with objective signs of inflammation as indicated by elevated C reactive protein (CRP) and/or magnetic resonance imaging (MRI) who have had an inadequate response to or are intolerant to nonsteroidal anti-inflammatory drugs (NSAIDs).

Ankylosing spondylitis (AS, radiographic axial spondyloarthritis).

Bimzelx is indicated for the treatment of adult patients with active ankylosing spondylitis who have responded inadequately or are intolerant to conventional therapy.

4.2 Dose and Method of Administration

The Instructions for Use included as a pack insert must be followed carefully.

Plaque psoriasis.

The recommended dose of Bimzelx for adult patients with plaque psoriasis is 320 mg (given as 2 subcutaneous injections of 160 mg each) at Week 0, 4, 8, 12, 16 and every 8 weeks thereafter.

Psoriatic arthritis.

The recommended dose of Bimzelx for adult patients with active psoriatic arthritis is 160 mg (given as one subcutaneous injection) every 4 weeks.
For psoriatic arthritis patients with coexistent moderate to severe plaque psoriasis, the use of the dose applicable to plaque psoriasis may be considered [i.e. 320 mg (given as 2 subcutaneous injections of 160 mg each) at Week 0, 4, 8, 12, 16 and every 8 weeks thereafter]. After 16 weeks, regular assessment of efficacy is recommended and if a sufficient clinical response in joints cannot be maintained, a switch to 160 mg every 4 weeks can be considered.

Axial spondyloarthritis (nr-axSpA and AS).

The recommended dose of Bimzelx for adult patients with active axial spondyloarthritis is 160 mg (given as one subcutaneous injection) every 4 weeks.

Method of administration.

Bimzelx is administered by subcutaneous injection. Suitable areas for injection include thigh, abdomen and upper arm. Injection sites should be rotated and injections should not be given into psoriasis plaques or areas where the skin is tender, bruised, erythematous, or indurated.
Bimzelx is for single use in one patient only. Discard any residue.

Special populations.

Overweight patients (plaque psoriasis).

For some patients with plaque psoriasis (including psoriatic arthritis with coexistent moderate to severe psoriasis) and a body weight ≥ 120 kg, 320 mg every 4 weeks after Week 16 may be considered (see Section 5.1 Pharmacodynamic Properties, Clinical trials).

Elderly population.

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

Renal and hepatic impairment.

Bimzelx has not been studied in these patient populations. Dose adjustments are not considered necessary based on pharmacokinetics (see Section 5.2 Pharmacokinetic Properties). No specific PK studies using Bimzelx have been pursued in patients with underlying impaired hepatic function.

Paediatric population.

The safety and efficacy of Bimzelx in children and adolescents below the age of 18 years has not been established. No data are available.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients (see Section 6.1 List of Excipients).
Live vaccines should not be given in patients treated with Bimzelx. No data are available on the response to live vaccines.

4.4 Special Warnings and Precautions for Use

Infections.

Bimzelx increases the risk of infections such as upper respiratory tract infections and mucocutaneous candidiasis (mostly oral, less frequent vulvovaginal, oesophageal) (see Section 4.8 Adverse Effects (Undesirable Effects)).
Caution should be exercised when considering the use of Bimzelx in patients with a chronic infection or a history of recurrent infection. Treatment with Bimzelx should not be initiated in patients with any clinically important active infection until the infection resolves or is adequately treated.
Patients treated with Bimzelx should be instructed to seek medical advice if signs or symptoms of clinically important chronic or acute infection and/or fungal infection occur. If a patient develops a clinically important infection or is not responding to standard therapy, the patient should be closely monitored and Bimzelx should not be administered until the infection resolves.

Pre-treatment evaluation for tuberculosis (TB).

No increased susceptibility to tuberculosis was reported from clinical studies. Prior to initiating treatment with Bimzelx, patients should be evaluated for TB infection. Bimzelx should not be given in patients with active TB. Patients receiving Bimzelx should be monitored for signs and symptoms of active TB. Anti-TB therapy should be considered prior to initiating Bimzelx in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed.

Inflammatory bowel disease.

Cases of new onset or exacerbations of inflammatory bowel disease have been reported during bimekizumab treatment. Caution should be exercised when prescribing Bimzelx to patients with inflammatory bowel disease. Patients should be monitored closely.

Hypersensitivity.

If a serious hypersensitivity reaction occurs, administration of Bimzelx should be discontinued immediately and appropriate therapy initiated.

Vaccinations.

Prior to initiating therapy with Bimzelx, consider completion of all appropriate immunizations according to current immunization guidelines.
Patients treated with Bimzelx may receive inactivated or non-live vaccinations. Healthy individuals who received a single 320 mg dose of Bimzelx two weeks prior to vaccination with an inactivated seasonal influenza vaccine had similar antibody responses compared to individuals who did not receive Bimzelx prior to vaccination.

Use in hepatic impairment.

Bimzelx has not been studied in these patient populations. Dose adjustments are not considered necessary based on pharmacokinetics (see Section 5.2 Pharmacokinetic Properties).

Use in renal impairment.

Bimzelx has not been studied in these patient populations. Dose adjustments are not considered necessary based on pharmacokinetics (see Section 5.2 Pharmacokinetic Properties).

Use in the elderly.

Based on population pharmacokinetic analysis with a limited number of elderly patients (n = 110 for age ≥ 65 years and n = 14 for age ≥ 75 years), apparent clearance (CL/F) in elderly patients and patients less than 65 years of age was similar. No dose adjustment is required.

Paediatric use.

The safety and efficacy of Bimzelx in children and adolescents below the age of 18 years has not be established. No data are available.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No CYP450 interaction studies have been performed in humans. There is no direct evidence for the role of IL-17A or IL-17F in the expression of CYP450 enzymes. Given that (1) bimekizumab, as an IgG1K mAb, is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG and (2) formation of some CYP450 enzymes which is suppressed by elevated levels of cytokines during inflammation (as in psoriasis), will be reversed by inflammatory suppressors, like IL-17A and IL-17F inhibitor bimekizumab, the resultant outcome will be a normalisation of CYP450 levels/activity. Extrapolation of the latter means that drugs metabolized by the CYP450 system may be co-administered with bimekizumab. However, monitoring of therapeutic plasma level and clinical effect of drugs with narrow therapeutic index (e.g. warfarin) metabolized via CYP450 system should be considered.
Population pharmacokinetic (PK) data analyses indicated that the clearance of bimekizumab was not impacted by concomitant administration of conventional disease modifying antirheumatic drugs (cDMARDs) including methotrexate or by prior exposure to biologics.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

The effect of bimekizumab on human fertility has not been evaluated. In animal studies, bimekizumab did not indicate harmful effects with respect to fertility as assessed by a lack of effects on reproductive organs, menstrual cycles or sperm in sexually mature cynomolgus monkeys that received bimekizumab for 26 weeks at a weekly SC dose of 200 mg/kg (dose resulting in 109 times the human exposure at 320 mg every 4 weeks based on AUC). The monkeys were not mated to evaluate functional fertility.
(Category C)
There are no adequate and well controlled studies in pregnant women to establish the safety of Bimzelx during pregnancy. Based on the mechanism of action of bimekizumab, the theoretical risk that use during pregnancy may affect neonatal immunity cannot be excluded. In an enhanced pre/postnatal development study in the cynomolgus monkey, bimekizumab showed no effects on gestation, parturition, infant survival, fetal or postnatal development when administered throughout organogenesis until parturition at a maternal dose of 50 mg/kg SC weekly resulting in 27 times the human exposure at 320 mg every 4 weeks based on AUC. At birth, serum bimekizumab concentrations in infant monkeys were comparable to those of mothers indicating placental transfer of bimekizumab. Bimzelx should be used in pregnancy only if the benefits clearly outweigh the potential risks.
It is not known whether bimekizumab is excreted in human milk or absorbed systemically after ingestion. As immunoglobulins can be excreted in human milk, caution should be exercised when Bimzelx is administered to a woman who is breast-feeding and a decision on whether to discontinue breast-feeding during treatment should be made.

4.7 Effects on Ability to Drive and Use Machines

Bimekizumab is not anticipated to have any influence on the ability to drive and use machines.

4.8 Adverse Effects (Undesirable Effects)

A total of 4821 patients have been treated with bimekizumab in blinded and open-label clinical studies in plaque psoriasis, psoriatic arthritis and axial spondyloarthritis (nr-axSpA and AS) representing 8733.0 patient-years of exposure. Of these, over 3900 patients were exposed to bimekizumab for at least one year.
Overall, the safety profile of bimekizumab is consistent across all indications.

Plaque psoriasis.

The most frequently reported adverse drug reactions (ADRs) were upper respiratory tract infections (most frequently nasopharyngitis) and oral candidiasis. See Table 1.

Psoriatic arthritis.

See Table 2 and Table 3.

Axial spondyloarthritis (axSpA).

See Table 4 and Table 5.

Other adverse reactions (< 1%).

Adverse drug reactions that occurred in < 1% but > 0.1% of subjects in the Bimzelx group and at a higher rate than in the placebo group through Week 16 were, tinea infection, herpes simplex, eczema, dermatitis contact, dyshidrotic eczema, intertrigo, dermatitis, otitis externa, otitis media, cutaneous and other mucosal candidiasis (including oesophageal).

Description of selected adverse reactions.

Infections. In the placebo-controlled period of Phase III clinical studies in plaque psoriasis, infections were reported in 36.0% of patients treated with bimekizumab for up to 16 weeks compared with 22.5% of patients treated with placebo. The majority of infections consisted of non-serious mild to moderate upper respiratory tract infections such as nasopharyngitis. There were higher rates of oral and oropharyngeal candidiasis in patients treated with bimekizumab consistent with the mechanism of action (7.3% and 1.2% respectively compared to 0% for placebo-treated patients). In the PS0015 study over the 48-week comparator controlled period, a higher incidence rate of oral candidiasis was observed in BKZ (19.3%) compared to secukinumab (3.0%) in PSO patients. The vast majority of cases were non-serious, mild or moderate in severity, and did not require treatment discontinuation.
Serious infections occurred in 0.3% of patients treated with bimekizumab and 0% treated with placebo.
Over the entire treatment period of Phase III studies in plaque psoriasis, infections were reported in 63.2% of patients treated with bimekizumab (120.4 per 100 patient-years). Serious infections were reported in 1.5% of patients treated with bimekizumab (1.6 per 100 patient-years) (see Section 4.4).
Infection rates observed in PsA and axSpA (nr-axSpA and AS) Phase III clinical studies were similar to those observed in plaque psoriasis.
In the placebo-controlled period, oral and oropharyngeal candidiasis rates in patients treated with bimekizumab were 2.3% and 0% respectively in PsA and 3.7% and 0.3% respectively in axSpA compared to 0% with placebo.
Neutropenia. Neutropenia was observed with bimekizumab in phase III clinical studies in plaque psoriasis. In the 16 weeks placebo-controlled period neutropenia grade 3/4 were observed at the same frequency of 0.6% in patients receiving bimekizumab or placebo. Over the entire treatment period of Phase III studies, neutropenia grade 3/4 were observed in 1% of patients treated with bimekizumab.
The frequency of neutropenia in PsA and axSpA (nr-axSpA and AS) clinical studies was similar to that observed in plaque psoriasis studies.
Most cases of neutropenia were transient and did not require treatment discontinuation. No serious infections were associated with neutropenia.
Hepatic transaminases.

Psoriatic arthritis.

During the placebo-controlled period, increased incidence of elevated hepatic transaminases was observed in psoriatic arthritis patients treated with bimekizumab compared to placebo.
Increase > 3 x upper limit of normal (ULN) and > 5 x ULN in hepatic transaminase levels were observed in the bimekizumab group (> 3-5 x ULN ALT: 0.9%, AST: 0.3%; > 5 x ULN ALT: 0.1%, AST: 0.4%), while no elevated ALT and AST was seen in the placebo group.
Elevations (mainly > 3 x ULN) in ALT and AST were also observed during the long-term treatment with bimekizumab.
The majority of ALT or AST elevations had confounding factors or alternative explanations, were transient and resolved.

Axial spondyloarthritis.

During the placebo-controlled period, hepatic transaminases elevations were observed in axial spondyloarthritis patients at a similar uncommon incidence in the bimekizumab and placebo group (> 3-5 x ULN ALT: 0.3% vs. 0.8%, AST: 0.9% vs. 0.4%; > 5 x ULN ALT: 0.6% vs. 0.4%, AST: 0.6% vs. 0.4%, respectively in the bimekizumab and placebo group).
Elevations (mainly > 3 x ULN) in ALT and AST were also observed during the long-term treatment with bimekizumab.
The majority of ALT or AST elevations had confounding factors or alternative explanations, were transient and resolved.
Immunogenicity. As with all therapeutic proteins, there is the potential for immunogenicity with bimekizumab. The detection of anti-drug antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of anti-drug 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 the incidence of antibodies to bimekizumab with the incidence of antibodies to other products may be misleading.

Plaque psoriasis.

Approximately 45% of plaque psoriasis patients treated with bimekizumab up to 56 weeks at the recommended dosing regimen (320 mg every 4 weeks up to Week 16 and 320 mg every 8 weeks thereafter) developed anti-drug antibodies. Of the patients who developed anti-drug antibodies, approximately 34% (16% of all patients treated with bimekizumab) had antibodies that were classified as neutralizing.

Psoriatic arthritis.

Approximately 31% of patients with psoriatic arthritis treated with bimekizumab at the recommended dosing regimen (160 mg every 4 weeks) up to 16 weeks had anti-drug antibodies. Of the patients with anti-drug antibodies, about 33% (10% of all patients treated with bimekizumab) had antibodies that were classified as neutralizing. By Week 52, approximately 47% of patients with PsA in the BE OPTIMAL study treated with bimekizumab at the recommended dosing regimen (160 mg every 4 weeks) had anti-drug antibodies. Of the patients in the BE OPTIMAL study with anti-drug antibodies, about 38% (18% of all patients treated with bimekizumab) had antibodies that were classified as neutralizing.

Axial spondyloarthritis.

nr-axSpA.

Approximately 57% of patients with nr-axSpA treated with bimekizumab up to 52 weeks at the recommended dosing regimen (160 mg every 4 weeks) had anti-drug antibodies. Of the patients with anti-drug antibodies, approximately 44% (25% of all patients treated with bimekizumab) had antibodies that were classified as neutralizing.

AS.

Approximately 44% of patients with AS treated with bimekizumab up to 52 weeks at the recommended dosing regimen (160 mg every 4 weeks) had anti-drug antibodies. Of the patients with anti-drug antibodies, approximately 44% (20% of all patients treated with bimekizumab) had antibodies that were classified as neutralizing.
Across all indications, no clinically meaningful impact on clinical response or safety profile was associated with anti-bimekizumab antibodies development.

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

Single doses of 640 mg intravenously or 640 mg subcutaneously, followed by 320 mg subcutaneously every two weeks for five doses have been administered in clinical studies without dose-limiting toxicity. In the event of overdose, it is recommended that the patient be monitored for any signs and symptoms of adverse reactions and appropriate symptomatic treatment be instituted immediately.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Bimekizumab is a humanised IgG1/κ monoclonal antibody with two identical antigen binding regions that bind and neutralise IL-17A, IL-17F and IL-17AF cytokines. Levels of IL-17A and IL-17F are elevated in several immune mediated inflammatory diseases and drive chronic inflammation and damage across multiple tissues. IL-17A and IL-17F cooperate and/or synergise with other inflammatory cytokines to induce inflammation. IL-17F is produced in significant amounts by innate immune cells. This production can be independent of IL-23. In human in vitro models, dual neutralisation of both IL-17A and IL-17F with bimekizumab suppresses the expression of inflammation related genes and proteins, inhibits the migration of inflammatory cells and pathological osteogenesis to a greater extent than inhibition of IL-17A alone.

Pharmacodynamic effects.

No formal pharmacodynamic (PD) studies have been conducted with bimekizumab.

Clinical trials.

Psoriasis - phase 3 pivotal studies. The safety and efficacy of bimekizumab was evaluated in 1480 patients with moderate to severe plaque psoriasis in three Phase III multicenter, randomized, placebo and/or active comparator controlled studies. Patients were at least 18 years of age, had a Psoriasis Area and Severity Index (PASI) score ≥ 12 and Body Surface Area (BSA) affected by PSO ≥ 10%, an Investigators Global Assessment (IGA) score ≥ 3 on a 5-point scale and were candidates for systemic psoriasis therapy and/or phototherapy. The efficacy and safety of bimekizumab were evaluated versus placebo and ustekinumab (BE VIVID - PS0009), versus placebo (BE READY - PS0013) and versus adalimumab (BE SURE - PS0008).
The BE VIVID study evaluated 567 patients for 52 weeks where patients were randomized to receive either bimekizumab 320 mg every 4 weeks, ustekinumab (45 mg or 90 mg, depending on patient weight, at baseline and Week 4 and then every 12 weeks), or placebo for an initial 16 weeks followed by bimekizumab 320 mg every 4 weeks.
The BE READY study evaluated 435 patients for 56 weeks. Patients were randomized to receive bimekizumab 320 mg every 4 weeks or placebo. At Week 16, patients who achieved a PASI 90 response entered the 40-week randomized withdrawal period. Patients initially randomized to bimekizumab 320 mg every 4 weeks were re-randomized to either bimekizumab 320 mg every 4 weeks or bimekizumab 320 mg every 8 weeks or placebo (i.e. withdrawal of bimekizumab). Patients initially randomized to placebo continued to receive placebo provided they were PASI 90 responders.
Patients who did not achieve a PASI 90 response at Week 16 entered an open-label escape arm and received bimekizumab 320 mg every 4 weeks for 12 weeks. Patients who relapsed (did not achieve PASI 75 response) during the randomized withdrawal period also entered the 12-week escape arm.
The BE SURE study evaluated 478 patients for 56 weeks. Patients were randomized to receive either bimekizumab 320 mg every 4 weeks through Week 56, bimekizumab 320 mg every 4 weeks through Week 16 followed by bimekizumab 320 mg every 8 weeks through Week 56 or adalimumab as per labeling recommendation through Week 24 followed by bimekizumab 320 mg every 4 weeks through Week 56.
Baseline characteristics were consistent across all 3 studies. Among those, the median baseline BSA was 20%, the median baseline PASI score was 18 and the baseline IGA score was severe in 33% of patients. The median baseline scores for Patient Symptoms Diary (PSD) pain, itch and scaling items ranged between 6 and 7 on a 0-10 points scale and the median baseline Dermatology Life Quality Index (DLQI) total score was 9.
Across all 3 studies, 38% of patients had received a prior biologic therapy; 23% had received at least one anti-IL17 agent and 13% had received at least one TNF-antagonist. Twenty-two percent were naïve to any systemic therapy (including non-biologic and biologic) and 39% of patients had received prior phototherapy or chemotherapy.
The efficacy of bimekizumab was evaluated with respect to impact on skin disease overall, specific body locations (scalp, nails and hand and foot), patient reported symptoms and impact on quality of life. The two co-primary end-points in all 3 studies were the proportion of patients who achieved 1) a PASI 90 response and 2) an IGA "clear or almost clear" (IGA 0/1 with at least two points improvement from baseline) response at Week 16. PASI 100, IGA 0 response at Week 16 and PASI 75 response at Week 4 were key secondary endpoints in all 3 studies.

Skin disease overall.

Treatment with bimekizumab resulted in significant improvement in the measures of disease activity compared to placebo, ustekinumab or adalimumab at Week 16. The key efficacy results are shown in Table 6.

Bimekizumab was associated with a rapid onset of efficacy. In BE VIVID, at Week 2 and Week 4, PASI 90 response rates were significantly higher for bimekizumab-treated patients (12.1% and 43.6% respectively) compared to placebo (1.2% and 2.4% respectively) and ustekinumab (1.2% and 3.1% respectively). See Figure 1.

In the BE VIVID study, at Week 52, bimekizumab-treated patients achieved significantly higher response rates than the ustekinumab-treated patients on the endpoints of PASI 90 (81.6% bimekizumab vs 55.8% ustekinumab, p < 0.001), IGA 0/1 (77.9% bimekizumab vs 60.7% ustekinumab, p < 0.001) and PASI 100 (64.2% bimekizumab vs 38.0% ustekinumab).
In the BE SURE study at Week 24, a significantly higher percentage of patients treated with bimekizumab achieved a PASI 90 and an IGA 0/1 responses as compared with adalimumab (85.6% and 86.5% respectively vs 51.6% and 57.9% respectively, p < 0.001). Among the 65 adalimumab nonresponders at Week 24 (< PASI 90), 78.5% achieved a PASI 90 response after 16 weeks of treatment with bimekizumab. No new safety findings were observed in patients who switched from adalimumab to bimekizumab. At Week 56, 70.2% of bimekizumab-treated patients achieved a PASI 100 response. See Figure 2.

The efficacy of bimekizumab was demonstrated regardless of age, gender, race, disease duration, body weight, PASI baseline severity and previous treatment with a biologic. Bimekizumab was efficacious in prior biologic exposed patients, including anti-TNF/ anti IL-17 and in systemic treatment-naïve patients.
Based on population PK/ PD analysis in patients with moderate to severe plaque psoriasis, some patients with higher body weight (≥ 120 kg) benefit from Bimzelx 320 mg every four weeks after the initial 16 weeks of treatment.
Across the entire bimekizumab Phase 3 psoriasis program, including 3 pivotal Phase 3 studies (BE SURE, BE VIVID, and BE READY) and the Phase 3b study (BE RADIANT - PS0015), a total of 1362 study participants were randomized to treatment with bimekizumab. Of these, 116 (8.5%) presented with a body weight ≥ 120 kg at Baseline.
A post-hoc analyses of efficacy for the subgroups of study participants weighing < 120 kg or ≥ 120 kg in the Initial Treatment Period (with bimekizumab 320 mg Q4W dosing from Week 0 to Week 16), pooled across all psoriasis Phase 3/3b studies is shown in Table 7.

Although the number of subjects in the ≥ 120 kg group is low, the data demonstrate that response rates were lower in patients weighing more than 120 kg compared with patients who weighed less and, represents a clinical correlation with the reduction in exposure as predicted by the PK/PD modelling.
The difference with bimekizumab 320 mg Q4W dosing between patients < 120 kg and patients ≥ 120 kg weights, however, is only numerical [9.3% for both PASI 90 and IGA 0/1]. There was no statistical analysis.
Based on the pooled analysis, greater increases in PASI 100 and IGA 0 were seen in the patients ≥ 120 kg beyond Week 16 with Q4W maintenance dosing compared to Q8W maintenance dosing. No statistical comparison was performed. Thus, it can be stated that increasing the dosing frequency in heavier patients has not been shown to result in greater statistically significant efficacy but may be used to increase plasma concentrations of bimekizumab in heavier patients.

Maintenance of response.

See Table 8.

Durability of PASI 90 response (after bimekizumab discontinuation).

See Figure 3.

In BE READY, for PASI 90 responders at Week 16 who were re-randomized to placebo and withdrawn from bimekizumab, the median time to relapse, defined as loss of PASI 75, was approximately 28 weeks (32 weeks after the last bimekizumab dose). Among these patients, 88.1% regained a PASI 90 response within 12 weeks of restarting treatment with bimekizumab 320 mg every 4 weeks.

Specific body locations.

Significant improvements were observed in psoriasis involving the scalp, nails and hands and feet in patients treated with bimekizumab at Week 16 (see Table 9).

Scalp IGA and palmoplantar IGA responses were maintained through Week 52/56. Nail psoriasis continued to improve beyond Week 16. In BE VIVID, at Week 52, 60.3% of patients treated with bimekizumab 320 mg every 4 weeks achieved complete nail clearance (mNAPSI 100). In BE READY, at Week 56, 67.7% and 69.8% of Week 16 PASI 90 responders achieved complete nail clearance with bimekizumab 320 mg every 8 weeks and bimekizumab 320 mg every 4 weeks respectively.

Health-related quality of life/patient reported outcomes.

Across all 3 studies, a greater proportion of patients treated with bimekizumab experienced no impact of psoriasis on their quality of life as measured by the Dermatology Life Quality Index (DLQI) compared to placebo and active comparator-treated patients at Week 16 (Table 10).

DLQI 0/1 responses continued to increase beyond Week 16 and then were maintained through Week 52/ 56. In BE VIVID, DLQI 0/1 response rate at Week 52 was higher in bimekizumab-treated patients (74.5%) compared with ustekinumab-treated patients (63.2%).
Psoriasis - phase 3b head to head study. The efficacy and safety of bimekizumab were also evaluated in a double-blind study compared with secukinumab, an IL-17A inhibitor, (BE RADIANT - PS0015). Patients were randomized to receive bimekizumab (N=373, 320 mg at Week 0, 4, 8, 12 and 16 (Q4W) followed by 320 mg every 4 weeks (Q4W/Q4W) or 320 mg every 8 weeks (Q4W/Q8W)) or secukinumab (N=370, 300 mg at Weeks 0,1, 2, 3, 4 followed by 300 mg every 4 weeks). Baseline characteristics were consistent with a population of moderate to severe plaque psoriasis patients with a median BSA of 19% and a median PASI score of 18.
Bimekizumab-treated patients achieved significantly higher response rates compared to secukinumab for the primary endpoint of PASI100 (complete skin clearance) at Week 16. Significantly higher response rates were also achieved with bimekizumab for the secondary endpoints of PASI 100 at Week 48 (for both Q4W/Q4W and Q4W/Q8W regimens) and PASI75 at Week 4. Comparative PASI response rates are presented in Table 11. Bimekizumab was associated with a rapid onset of efficacy. Differences in response rates between bimekizumab and secukinumab-treated patients were noted as early as Week 1 for PASI 75 (7.2% and 1.4% respectively) and as early as Week 2 for PASI 90 (7.5% and 2.4% respectively).

Bimekizumab and secukinumab PASI 100 response rates through Week 48 are presented in Figure 4.

Psoriatic arthritis. The safety and efficacy of bimekizumab were evaluated in 1112 adult patients (at least 18 years of age) with active psoriatic arthritis (PsA) in two multicenter, randomized, double-blind, placebo-controlled studies (PA0010 - BE OPTIMAL and PA0011- BE COMPLETE). The BE OPTIMAL study included an active reference treatment arm (adalimumab, N=140). For both studies, patients had a diagnosis of active psoriatic arthritis for at least 6 months based on the Classification Criteria for Psoriatic Arthritis (CASPAR) and had active disease with tender joint count (TJC) ≥ 3 and swollen joint count (SJC) ≥ 3. Patients had a diagnosis of PsA for a median of 4.6 years. Patients with each subtype of PsA were enrolled in these studies, including polyarticular symmetric arthritis, oligoarticular asymmetric arthritis, distal interphalangeal joint predominant, spondylitis predominant and arthritis mutilans. At baseline, 55.9% of patients had ≥ 3% Body Surface Area (BSA) with active plaque psoriasis with 10.4% of patients having moderate to severe plaque psoriasis. 31.9% and 12.3% had enthesitis and dactylitis at baseline respectively. The primary efficacy endpoint in both studies was the American College of Rheumatology (ACR) 50 response at Week 16.
The BE OPTIMAL study evaluated 852 patients not previously exposed to any biologic disease-modifying anti-rheumatic drug (bDMARD) for the treatment of psoriatic arthritis or psoriasis. Patients were randomized (3:2:1) to receive bimekizumab 160 mg every 4 weeks up to Week 52 or placebo up to Week 16 followed by bimekizumab 160 mg every 4 weeks up to Week 52 or an active reference treatment (adalimumab 40 mg every 2 weeks) up to Week 52. In this study, 78.3% of patients had received prior treatment with ≥ 1 conventional DMARDs (cDMARDs) and 21.7% of patients had no prior treatment with cDMARDs. At baseline, 58.2% of patients were receiving concomitant methotrexate (MTX), 11.3% were receiving concomitant cDMARDs other than MTX, and 30.5% were receiving no cDMARDs.
The BE COMPLETE study evaluated 400 patients with an inadequate response (lack of efficacy) or intolerance to treatment with 1 or 2 tumor necrosis factor alpha inhibitors (anti-TNFα - IR) for either psoriatic arthritis or psoriasis. Patients were randomized (2:1) to receive bimekizumab 160 mg every 4 weeks or placebo up to Week 16. At baseline, 42.5% of patients were receiving concomitant MTX, 8.0% were receiving concomitant cDMARDs other than MTX, and 49.5% were receiving no cDMARDs.

Clinical response.

In bDMARD-naïve patients (BE OPTIMAL) and anti-TNFα IR patients (BE COMPLETE) treatment with bimekizumab resulted in significant improvement in signs and symptoms and measures of disease activity compared to placebo at Week 16, with similar response rates seen in both patient populations (see Table 12). Clinical responses were sustained up to Week 52 in BE OPTIMAL as assessed by ACR 20, ACR 50, ACR 70, MDA, PASI 90, PASI 100 and ACR 50 / PASI 100.

In BE OPTIMAL, at Week 16, in patients treated with adalimumab (active reference treatment without any statistical comparison to bimekizumab or placebo performed), 45.7%, 41.2% and 45.0% achieved ACR50, PASI 90 and MDA respectively.
Improvements from baseline were shown in all individual ACR components with bimekizumab at Week 16 (see Table 13) and were sustained up to Week 52 in BE OPTIMAL.

Bimekizumab was associated with a rapid onset of efficacy in both bDMARD-naïve (BE OPTIMAL) and anti-TNFα-IR (BE COMPLETE) patients. In BE OPTIMAL, as early as Week 2 (first post-baseline visit), the ACR 20 response rate was higher in the bimekizumab-treated group (27.1%) compared with the placebo group (7.8%). By Week 4, after one dose, 17.6% of patients achieved an ACR 50 with bimekizumab compared to 3.2% with placebo. In BE COMPLETE, after one dose, as early as Week 4 (first post-baseline visit) the ACR 20 and ACR 50 response rates were higher for the bimekizumab-treated group (42.7% and 16.1%, respectively) compared with the placebo group (6.8% and 1.5%, respectively). See Figure 5 and Figure 6.

In BE OPTIMAL, of bimekizumab-treated patients who achieved an ACR 50 response at Week 16, 87.2% maintained this response at Week 52.
In BE OPTIMAL at Week 52, 65.5% of bimekizumab-treated patients achieved complete nail clearance (mNAPSI resolution in patients with mNAPSI > 0 at baseline).
The efficacy and safety of bimekizumab was demonstrated regardless of age, gender, race, baseline body weight, baseline psoriasis involvement, baseline CRP, disease duration, and prior cDMARDs use.
In both studies, similar responses were observed with bimekizumab regardless of whether patients were on concomitant cDMARDs, including MTX, or not.
The modified Psoriasis Arthritis Response Criteria (PsARC) is a specific composite responder index comprising of tender joint count, swollen joints count, patient and physician global assessment. The proportion of patients achieving modified PsARC at Week 16 was higher in the bimekizumab-treated patients compared to placebo (80.3% versus 40.2% in BE OPTIMAL and 85.4% versus 30.8% in BE COMPLETE). In addition, the proportion of patients achieving a low disease activity or remission as measured by the Disease Activity Index for Psoriatic Arthritis (DAPSA score less or equal to 14) was higher in the bimekizumab-treated patients compared to placebo in both studies. PsARC response and DAPSA response were sustained up to Week 52 in BE OPTIMAL.
Patients with axial involvement at baseline (74.1% of patients in BE OPTIMAL and 75% in BE COMPLETE), (defined as a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4) showed greater improvement from baseline in BASDAI compared with placebo at Week 16. Improvement achieved at Week 16 was sustained up to Week 52 in BE OPTIMAL.

Radiographic response.

In BE OPTIMAL, inhibition of progression of structural damage was assessed radiographically and expressed as the change from baseline in the Van der Heijde modified total Sharp Score (vdHmTSS) (see Table 14) and its components, the Erosion Score (ES) and the Joint Space Narrowing score (JSN) at Week 16.

Bimekizumab significantly inhibited the rate of progression of joint damage at Week 16 in both the population with elevated hs-CRP and/or at least 1 bone erosion at baseline and the overall population compared to placebo. The percentage of patients with no radiographic joint damage progression (defined as a change from baseline in mTSS of ≤ 0.5) from randomization to Week 16 was 83.9% for bimekizumab and 77.5% for placebo in the population with elevated hs-CRP and/or at least 1 bone erosion. Similar responses were achieved in the overall population (85.7% for bimekizumab and 78.8% for placebo). The percentage of patients with no radiographic joint damage progression was sustained up to Week 52 with bimekizumab in both patient populations.

Physical function and other health-related outcomes.

Both bDMARD-naïve (BE OPTIMAL) and anti-TNFα-IR (BE COMPLETE) patients receiving bimekizumab showed significant improvement from baseline in physical function compared to placebo patients at Week 16 (p < 0.001) as assessed by the HAQ-DI (see Table 13). In both studies, a greater proportion of patients achieved a clinically meaningful reduction of at least 0.35 in HAQ-DI score from baseline in the bimekizumab group compared with placebo at Week 16. Response was sustained up to Week 52 in BE OPTIMAL.
Bimekizumab-treated patients reported significant improvement from baseline in the Short Form-36 item Health Survey Physical Component Summary (SF-36 PCS) score at Week 16 compared to placebo (LS Mean change from baseline: 6.3 versus 1.9, p < 0.001 in BE OPTIMAL and 6.2 versus 0.1, p < 0.001 in BE COMPLETE).
In both studies, bimekizumab-treated patients reported meaningful reduction from baseline in fatigue as measured by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score at Week 16 compared to placebo. Meaningful improvement from baseline was also observed in PsA specific health-related quality of life as measured by the Psoriatic Arthritis Impact of Disease-12 (PsAID-12) score in the bimekizumab-treated group compared to the placebo group at Week 16.
Bimekizumab-treated patients reported greater improvement in work productivity and daily activity at Week 16 as reported by the Work Productivity and Activity Impairment Questionnaire-specific health problem (WPAI-SHP) compared to placebo.
Improvements in HAQ-DI score, SF-36 PCS score, FACIT-Fatigue score, PsAID-12 score and WPAI-SHP achieved at Week 16 were sustained up to Week 52 in BE OPTIMAL.
Axial spondyloarthritis. The efficacy and safety of bimekizumab were evaluated in 586 adult patients (at least 18 years of age) with active axial spondyloarthritis (axSpA) in two multicenter, randomized, double-blind, placebo-controlled studies, one in non-radiographic axial spondyloarthritis (nr-axSpA) and one in ankylosing spondylitis (AS), also known as radiographic axSpA. The primary endpoint in both studies was the percentage of patients achieving an Assessment of SpondyloArthritis International Society (ASAS) 40 response at Week 16. Consistent results were seen across both patient populations (nr-axSpA and AS).
The BE MOBILE 1 study (AS0010) evaluated 254 patients with active nr-axSpA. Patients had axSpA (age of symptoms onset < 45 years) meeting the ASAS classification criteria and had active disease as defined by a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4 and spinal pain ≥ 4 on a 0 to 10 numeric rating scale (NRS) (from BASDAI Item 2) and no evidence of radiographic changes in the sacroiliac joints that would meet the modified New York criteria for AS. Patients also had objective signs of inflammation as indicated by elevated C-reactive protein (CRP) level and/or evidence of sacroiliitis on Magnetic Resonance Imaging (MRI) as well as a history of inadequate response to 2 different non-steroidal anti-inflammatory drugs (NSAIDs) or intolerance or contraindication to NSAIDs. Patients were randomized (1:1) to receive bimekizumab 160 mg every 4 weeks up to Week 52 or placebo up to Week 16 followed by bimekizumab 160 mg every 4 weeks up to Week 52. At baseline, patients had symptoms of nr-axSpA for a mean of 9 years (median of 5.5 years). 10.6% of patients were previously treated with an anti-TNFα agent.
The BE MOBILE 2 study (AS0011) evaluated 332 patients with active AS determined by documented radiologic evidence (X-ray) fulfilling the Modified New York criteria for AS. Patients had active disease as defined by a BASDAI ≥ 4 and spinal pain ≥ 4 on a 0 to 10 numeric rating scale (NRS) (from BASDAI Item 2). Patients had to have a history of inadequate response to 2 different NSAIDs or intolerance or contraindication to NSAIDs. Patients were randomized (2:1) to receive bimekizumab 160 mg every 4 weeks up to Week 52 or placebo up to Week 16 followed by bimekizumab 160 mg every 4 weeks up to Week 52. At baseline, patients had symptoms of AS for a mean of 13.5 years (median of 11 years). 16.3% of patients were previously treated with an anti-TNFα agent.

Clinical response.

Treatment with bimekizumab resulted in significant improvement in signs and symptoms and measures of disease activity compared to placebo at Week 16 in both nr-axSpA and AS patient populations (see Table 15). Clinical responses were sustained up to Week 52 in both patient populations as assessed by all the endpoints presented in Table 15.

Improvements in the components of the ASAS 40 response criteria and other measures of efficacy are shown in Table 16. Improvements achieved at Week 16 were sustained up to Week 52 in both patient populations.

Bimekizumab was associated with a rapid onset of efficacy in both nr-axSpA and AS patient population.
In BE MOBILE 1, as early as Week 1, the ASAS 20 and ASAS 40 response rates in bimekizumab-treated patients were greater than in placebo-treated patients (31.3% versus 11.9% and 16.4% versus 1.6%, respectively). Bimekizumab was also associated with a rapid decrease in systemic inflammation as measured by the hs-CRP levels. As early as Week 2 (first measurement of hs-CRP), the geometric mean hs-CRP ratio to baseline was lower in the bimekizumab-treated patients (0.4) compared to placebo (0.9).
In BE MOBILE 2, as early as Week 2, the ASAS 20 and ASAS 40 response rates in bimekizumab-treated patients were greater than in placebo-treated patients (43.4% versus 25.2% and 16.7% versus 7.2% respectively). Bimekizumab was also associated with a rapid decrease in systemic inflammation as measured by hs-CRP levels. As early as Week 2 (first measurement of hs-CRP), the geometric mean hs-CRP ratio to baseline was lower in the bimekizumab-treated patients (0.4) compared to placebo (0.9). See Figure 7 and Figure 8.

In an integrated analysis of BE MOBILE 1 and BE MOBILE 2, of bimekizumab-treated patients who achieved an ASAS 40 response at Week 16, 82.1% maintained this response at Week 52.
The efficacy of bimekizumab was demonstrated regardless of age, gender, race, disease duration, baseline inflammation status, baseline ASDAS and concomitant cDMARDs. Patients with a BMI ≥ 30 kg/m² may take longer time to achieve clinical response.
Similar response in ASAS 40 was seen in patients regardless of prior anti-TNFα exposure.
At Week 16, among patients with enthesitis at baseline, the proportion of patients (NRI) with enthesitis resolution as assessed by the Maastricht Ankylosing Spondylitis Enthesitis (MASES) index was greater with bimekizumab compared to placebo (BE MOBILE 1: 51.1% versus 23.9% and BE MOBILE 2: 51.5% versus 32.8%). Response with bimekizumab was sustained up to Week 52 in both studies (BE MOBILE 1: 54.3% and BE MOBILE 2: 50.8%).

Reduction of inflammation.

Bimekizumab reduced inflammation as measured by hs-CRP (see Table 16) and as assessed by MRI in an imaging sub-study. Signs of inflammation were assessed by MRI at baseline and Week 16 and expressed as change from baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) score for sacroiliac joints and Ankylosing Spondylitis spine Magnetic Resonance Imagine-activity (ASspiMRI-a score in the Berlin modification) for the spine. Reduction of inflammatory signs in both sacroiliac joints and the spine was observed in patients treated with bimekizumab as compared with placebo (see Table 17). Reduction of inflammation as measured by hs-CRP and as assessed by MRI was sustained to Week 52.

Physical function and other health-related outcomes.

Patients treated with bimekizumab showed significant improvement from baseline in physical function as assessed by the BASFI (see Table 16). Patients treated with bimekizumab reported significant improvement from baseline compared to placebo-treated patients in SF-36 PCS score (LS Mean change from baseline at Week 16 in BE MOBILE 1: 9.3 versus 5.4, p < 0.001 and in BE MOBILE 2: 8.5 versus 5.2, p < 0.001).
Patients treated with bimekizumab reported significant improvement from baseline in health-related quality of life as measured by the AS Quality of Life Questionnaire (ASQoL) compared to placebo (LS Mean change from baseline at Week 16 in BE MOBILE 1: -4.9 versus -2.3, p < 0.001 and in BE MOBILE 2: -4.6 versus -3.0, p < 0.001) as well as meaningful reduction in fatigue as assessed by the FACIT-Fatigue score (Mean change from baseline at Week 16 in BE MOBILE 1: 8.5 for bimekizumab versus 3.9 for placebo and in BE MOBILE 2: 8.4 for bimekizumab versus 5.0 for placebo).
Bimekizumab-treated patients reported greater improvement in work productivity and daily activities at Week 16 as reported by the WPAI-SHP compared to placebo.
Improvements in BASFI, SF-36 PCS score, ASQoL, FACIT-Fatigue score and WPAI-SHP achieved at Week 16 were sustained up to Week 52 in both studies.

Extra-articular manifestation.

In pooled data from BE MOBILE 1 (nr-axSpA) and BE MOBILE 2 (AS), at Week 16, the proportion of patients developing a uveitis event was lower with bimekizumab (0.6%) compared to placebo (4.6%). The incidence of uveitis remains low in bimekizumab-treated patients (1.2/100 patient-years in the pooled phase 2/3 studies).

5.2 Pharmacokinetic Properties

The pharmacokinetic (PK) properties of bimekizumab were similar in patients with plaque psoriasis, psoriatic arthritis and axial spondyloarthritis (nr-axSpA and AS).
Bimekizumab exhibited dose-proportional pharmacokinetics in patients with plaque psoriasis over a dose range from 64 mg to 480 mg following multiple subcutaneous administrations, with apparent clearance being independent of dose.

Absorption.

Based on population PK analysis, following a single subcutaneous dose of 320 mg in plaque psoriasis patients, bimekizumab reached a median (2.5th and 97.5th percentile) peak plasma concentration of 25 (12-50) microgram/mL, between 3 and 4 days post dose.
Population pharmacokinetic analysis showed that bimekizumab was absorbed with an average absolute bioavailability of 70.1% in healthy volunteers.

Distribution.

Based on population PK analyses, the median (coefficient of variation %) volume of distribution (V/F) at steady state was 11.2 (30.5%) L in plaque psoriasis patients.

Metabolism.

Bimekizumab is a monoclonal antibody and is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous immunoglobulins.

Excretion.

Based on population PK analyses, the median (coefficient of variation %) apparent clearance (CL/F) of bimekizumab was 0.337 L/day (32.7%) and the mean terminal elimination half-life of bimekizumab was 23 days in clinical studies in patients with plaque psoriasis.
Based on simulated data, the median (2.5th and 97.5th percentile) peak and trough concentration at steady-state following subcutaneous administration of 320 mg every 4 weeks are 43 (20-91) microgram/mL and 20 (7-50) microgram/mL respectively and steady-state is reached after approximately 16 weeks with every 4 weeks dosing regimen. Compared with exposure after a single dose, the population PK analysis showed that patients exhibited a 1.74-fold increase in peak plasma concentrations and area under the curve (AUC) following repeated four weekly dosing.
After switching from the 320 mg every 4 weeks dosing regimen to 320 mg every 8 weeks dosing regimen at Week 16, steady-state is achieved approximately 16 weeks after the switch. Median (2.5th and 97.5th percentile) peak and trough plasma concentrations are 30 (14 -60) microgram/mL and 5 (1-16) microgram/mL respectively.

Pharmacokinetic/pharmacodynamic relationship.

A population PK/PD model was developed using all available data in moderate to severe plaque psoriasis patients. The analysis showed that higher bimekizumab concentrations are related to better Psoriasis Area and Severity Index (PASI) and Investigators Global Assessment (IGA) response and a dose of 320 mg at Week 0, 4, 8, 12, 16 and every 8 weeks thereafter provides maximum benefit to the majority of moderate to severe plaque psoriasis patients (see Special populations, Body weight).

Special populations.

Elderly.

Based on population PK analysis with a limited number of elderly patients (n = 337 for age ≥ 65 years and n = 45 for age ≥ 75 years), apparent clearance (CL/F) in elderly patients and patients less than 65 years of age was similar. No dose adjustment is required.

Renal or hepatic impairment.

No specific studies have been conducted to determine the effect of renal or hepatic impairment on the pharmacokinetics of bimekizumab. Caution should be taken in people with hepatic and renal dysfunction, due to the absence of data from these populations in the studies. The renal elimination of intact bimekizumab, an IgG monoclonal antibody, is expected to be low and of minor importance. Similarly, IgGs are mainly eliminated via intracellular catabolism and hepatic impairment is not expected to influence clearance of bimekizumab. Based on population PK analyses, hepatic function markers (ALT/ bilirubin) did not have any impact on bimekizumab clearance in patients with plaque psoriasis.

Body weight.

Population PK modelling indicated that exposure decreased as body weight increased. The average plasma concentration in adult patients weighing ≥ 120 kg following a 320 mg subcutaneous injection was predicted to be at least 30% lower than in adult patients weighing 90 kg. Dose adjustment may be appropriate in some patients (see Section 4.2 Dose and Method of Administration).

Race/gender.

No clinically meaningful differences in bimekizumab exposure were observed in Japanese or Chinese subjects compared to Caucasian subjects in a clinical PK study. No dose adjustment is required.
Population PK modelling indicated females may have 10% faster apparent clearance (CL/F) compared to males and it is not clinically meaningful. No dose adjustment is required.

5.3 Preclinical Safety Data

Genotoxicity.

No genotoxicity studies were conducted with bimekizumab. Monoclonal antibodies are not expected to damage DNA or chromosomes.

Carcinogenicity.

No carcinogenicity studies were conducted with bimekizumab.

6 Pharmaceutical Particulars

6.1 List of Excipients

The inactive ingredients are glycine, sodium acetate trihydrate, acetic acid, polysorbate 80, water for injection.

6.2 Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

6.3 Shelf Life

36 months.

6.4 Special Precautions for Storage

Store in a refrigerator (2°C - 8°C).
Do not freeze.
Keep the pre-filled syringe or pen in the outer carton in order to protect from light.
The Bimzelx pre-filled syringe and pre-filled pen may be stored at room temperature (up to 25°C) for a single period of maximum 30 days with protection from light. Once removed from the refrigerator and stored under these conditions, discard after 30 days or by the expiry date printed on the container, whichever occurs first. A field for the date is provided on the carton to record the date removed from the refrigerator.

6.5 Nature and Contents of Container

Bimzelx 160 mg solution for injections in pre-filled syringe.

One mL pre-filled syringe (type I glass) with a fluoropolymer-laminated bromobutyl rubber stopper, staked 27 G, ½" thin wall needle, and a polypropylene rigid needle shield assembled in a passive safety device.
Pack size of 2 pre-filled syringes.

Bimzelx 160 mg solution for injections in pre-filled pen.

One mL pre-filled pen containing a pre-filled syringe (type I glass) with a fluoropolymer-laminated bromobutyl rubber stopper, staked 27 G, ½" thin wall needle, and a polypropylene rigid needle shield.
Pack size of 2 pre-filled pens.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Chemical name: Immunoglobulin G1, anti-IL17A and anti-IL17F.
Nominal theoretical molecular mass: approximately 149,886 Da^a.
^a Theoretical mass based on presence of G0F glycans and clipped heavy chain C-terminal modifications.

Chemical structure.

CAS number.

1418205-77-2.

7 Medicine Schedule (Poisons Standard)

S4.

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