Consumer medicine information

Cosentyx

Secukinumab

BRAND INFORMATION

Brand name

Cosentyx

Active ingredient

Secukinumab

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Cosentyx.

What is in this leaflet

This leaflet answers some common questions about COSENTYX.

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

The information in this leaflet was last updated on the date listed on the final page. More recent information on the medicine may be available.

You should ensure that you speak to your pharmacist or doctor to obtain the most up to date information on the medicine. You can also download the most up to date leaflet from www.novartis.com.au. Those updates may contain important information about the medicine and its use of which you should be aware.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking COSENTYX 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 COSENTYX is used for

COSENTYX is used for the treatment of the following inflammatory diseases:

  • Plaque psoriasis
  • Psoriatic arthritis
  • Ankylosing spondylitis

Plaque psoriasis
COSENTYX is used to treat a skin condition called 'plaque psoriasis' in adults.

Plaque psoriasis causes inflammation of the skin.

COSENTYX is used in adults with moderate to severe plaque psoriasis.

Psoriatic arthritis
COSENTYX is used to treat a condition called 'psoriatic arthritis'. The condition is an inflammatory disease of the joints, often accompanied by psoriasis.

Ankylosing spondylitis
COSENTYX is used to treat a condition called 'ankylosing spondylitis' in adults. The condition is an inflammatory disease primarily affecting the spine which causes inflammation of the spinal joints.

In patients with plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis the body produces increased amounts of a protein called IL-17A. This may lead to symptoms such as itching, pain, scaling in psoriasis, swollen and tender joints in psoriatic arthritis, and pain in the spine in ankylosing spondylitis.

COSENTYX contains the active substance secukinumab. This ingredient is a fully-human monoclonal antibody and belongs to a group of medicines called interleukin (IL) inhibitors. Monoclonal antibodies are proteins that recognise and bind specifically to certain proteins in the body.

COSENTYX works by neutralising the activity of the IL-17A protein, which is present at increased levels in conditions such as psoriasis, psoriatic arthritis, and ankylosing spondylitis. It will reduce the inflammation and other symptoms of the condition.

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

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed it for another reason.

COSENTYX is not recommended for children and adolescents (under 18 years of age) because it has not been studied in this age group.

COSENTYX may be used by people aged 65 years and over.

COSENTYX is available only with a doctor's prescription and is not addictive.

Before you have COSENTYX

When you must not take it

Do not take COSENTYX if you have had a severe allergic reaction to secukinumab or any of the other ingredients listed at the end of this leaflet.

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

Do not take COSENTYX if you have an active infection which your doctor thinks is important.

Do not take COSENTYX if there are visible signs of deterioration.

If you think you may be allergic, ask your doctor for advice before using COSENTYX.

Do not take this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should start taking this medicine, talk to your doctor.

Before you start to have it

If any of these apply to you, tell your doctor or pharmacist before using COSENTYX:

  • you currently have an infection or if you have long-term or repeated infections
  • you have tuberculosis
  • you have inflammatory bowel disease (Crohn's disease or ulcerative colitis)
  • you had a recent vaccination or if you will receive a live vaccine during treatment with COSENTYX

Tell your doctor if you are pregnant, think that you may be pregnant or are planning to have a baby. COSENTYX is not recommended during pregnancy unless the benefits clearly outweigh the potential risks.

Tell your doctor if 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 COSENTYX.

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.

Tell your doctor or pharmacist if you:

  • are taking a blood thinning medicine called warfarin.
  • are taking, have recently taken or might take any other medicines.
  • have recently had or are going to have a vaccination. You should not receive certain types of vaccines (live vaccines) while using COSENTYX.

Such medicines may be affected by COSENTYX or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine.

How COSENTYX is given

Follow all directions given to you by your doctor, nurse or pharmacist carefully. They may differ from the information contained in this leaflet.

Always use COSENTYX as your doctor has told you. You should check with your doctor, nurse or pharmacist if you are not sure.

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

The injection may be given by your doctor or nurse or you may be taught how to inject yourself with the medicine.

You and your doctor should decide if you should inject COSENTYX yourself. It is important not to try to inject yourself until you have been trained by your doctor, nurse or pharmacist. A caregiver may also give you your COSENTYX injection after proper training.

If you do not understand the instructions on the label ask your doctor or pharmacist for help.

How much is given

Your doctor will decide how much COSENTYX you need.

Plaque psoriasis
The recommended dose is 300 mg by subcutaneous injection with initial loading dose at Weeks 0, 1, 2, 3, and 4 followed by the same dose every month. Each 300 mg dose is given as two sub-cutaneous injections of 150 mg.

Psoriatic arthritis
The recommended dose is 150 mg by subcutaneous injection with initial dosing at Weeks 0, 1, 2, 3, and 4 followed by the same dose every month. Based on your response, your doctor may increase the dose to 300 mg.

For patients who did not respond well to medicines called tumour necrosis factor (TNF) blockers or patient who also have moderate to severe plaque psoriasis, the recommended dose is 300 mg by subcutaneous injection with initial dosing at Weeks 0, 1, 2, 3, and 4 followed by the same dose every month. Each 300 mg dose is given as two subcutaneous injections of 150 mg.

COSENTYX may be administered with or without methotrexate.

Ankylosing spondylitis
The recommended dose is 150 mg by subcutaneous injection with initial dosing at Weeks 0, 1, 2, 3, and 4 followed by the same dose every month. Based on your response, your doctor may increase the dose to 300 mg. Each 300 mg dose is given as two subcutaneous injections of 150 mg.

Do not exceed the recommended dose.

Choosing the injection sites

The injection sites are where the skin will be pierced to administer the subcutaneous injection.

The recommended site is the front of your thighs. You may also use the lower abdomen, but not the area five centimetres around the navel (belly button). If a caregiver is giving you the injection, the outer upper arms may also be used (Shown in grey in the diagram for illustrative purposes).

Choose a different site each time you give yourself an injection.

Do not inject into areas where the skin is tender, bruised, red, scaly or hard.

Avoid areas with scars or stretch marks

Injecting COSENTYX yourself

Discuss with your doctor whether or not you will inject COSENTYX yourself.

Do not try to inject yourself if you have not been properly trained or if you are not sure how to do it.

After proper training in injection technique, your doctor will tell you that you may inject it yourself.

Read the following instructions on how to use the prefilled pen all the way through before removing COSENTYX from the refrigerator. These instructions are to help you to inject correctly.

How to use the prefilled pens

Read ALL the way through these instructions before injecting. These instructions will help you to inject correctly using the pen.

For a more comfortable injection, take the carton containing two pens out of the refrigerator 15 to 30 minutes before injecting.

This will enable them to reach room temperature. COSENTYX should be administered within one hour after removal from 2°C to 8°C storage.

During the injection you will hear 2 loud clicks. The first click indicates that the injection has started. Several seconds later a second click will indicate that the injection is almost finished.

You must keep holding the pen firmly against your skin until you see a green indicator fill the window and stop moving.

Before your injection, gather together the necessary items not included in the COSENTYX pack:

  • alcohol swabs
  • clean, dry cotton swab or gauze
  • sharps disposal container

  1. When you are ready to use the pens, wash your hands thoroughly with soap and water.
  2. Inspect the pen.
    The liquid should be clear. Its colour may vary from colourless to slightly yellow. You may see a small air bubble, which is normal.

Do NOT use the pen if the liquid contains easily visible particles, is cloudy or is distinctly brown.
  1. Find a clean, comfortable area.

Using a circular motion, clean the injection site with the alcohol swab.
Leave it to dry before injecting. Do not touch the cleaned area again before injecting.
  1. Only remove the cap when you are ready to use the pen.

Twist off the cap in the direction of the arrows. Once removed, throw away the cap.
Use the pen within 5 minutes of removing the cap. Do not try to re-attach the cap.
  1. Hold the pen at 90 degrees to the cleaned injection site.
    Ensure the inspection window on the pen is visible before injecting.

  1. Press the pen firmly against the skin to start the injection.

The first click indicates the injection has started.
Keep holding the pen firmly against your skin.
The green indicator shows the progress of the injection.
  1. Listen for the second click.
    This indicates the injection is almost complete.

After the injection, check the green indicator fills the window and has stopped moving. The pen can now be removed.
  1. Check the green indicator fills the window.

This means the medicine has been delivered.
Contact your doctor if the green indicator is not visible.
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 used pen in a sharps disposal container (i.e. a puncture-resistant closable container, or similar). Never try to reuse the spent pen.

  1. If you have been prescribed a 300 mg dose and therefore a second injection is required, choose a different site and repeat steps 2 to 9 with the second pen.

How long to take COSENTYX

This is a long-term treatment. Keep taking this medicine for as long as your doctor tells you.

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

If you use more COSENTYX than you should (overdose)

If you or anyone else accidentally received more COSENTYX than you should or 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 forget to have it

If you have forgotten to inject a dose of COSENTYX, 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 have your medicine, ask your pharmacist for some hints.

While you are taking COSENTYX

Things you must do

Discontinue treatment and tell your doctor or pharmacist immediately if you get any of these symptoms during treatment with COSENTYX.

Signs or symptoms of a potentially serious infection. These 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
  • burning when passing urine

Signs or symptoms of an allergic reaction. These may include:

  • difficulty breathing or swallowing
  • low blood pressure, which can cause dizziness or light-headedness
  • swelling of the face, lips, mouth or throat
  • severe itching of the skin, with a red rash or raised bumps

Keep all of your doctor's appointments so that your progress can be checked. Your doctor will do tests from time to time to make sure the medicine is working and to prevent unwanted side effects.

Your doctor will decide if and when you may restart the treatment.

If you need to be vaccinated, tell your doctor you are taking COSENTYX before you have the vaccination. Live vaccines will not be suitable for you.

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking COSENTYX.

Tell any other doctors, dentists, and pharmacists who treat you that you are taking this medicine.

Things you must not do

Never leave the prefilled pen lying around where others might tamper with it.

Do not open the sealed box until you are ready to use COSENTYX.

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

Do not use the prefilled pen if either the seal on the outer box or the seal of the blister are broken. It may not be safe for you to use.

Do not shake the prefilled pen.

Do not use the pen if it has been dropped with the cap 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 COSENTYX prefilled pens immediately after use in a sharps container. The COSENTYX prefilled pen should never be re-used.

If you stop using COSENTYX

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

Side effects

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

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking COSENTYX.

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

You may need medical attention if you get some of the side effects.

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

Some side effects are very common (These side effects may affect more than 1 in every 10 people)

  • Upper respiratory tract infections with symptoms such as sore throat and stuffy nose (nasopharyngitis, rhinitis)

Some side effects are common (These side effects may affect up to 1 in every 10 people)

  • Cold sores (oral herpes)
  • Diarrhoea
  • Runny nose (rhinorrhoea)
  • Hives
  • Headache
  • Nausea
  • Itchy rash (urticaria)

Some side effects are uncommon (These side effects may affect up to 1 in every 100 people)

  • Oral thrush (oral candidiasis)
  • Signs of low levels of white blood cells such as fever, sore throat or mouth ulcers due to infections (neutropenia)
  • Athlete's foot (tinea pedis)
  • Infection of the external ear (otitis externa)
  • Discharge from the eye with itching, redness and swelling (conjunctivitis)
  • Painful period
  • Some side effects are rare (may affect in to 1 in 1,000 people)
  • Severe allergic reaction with shock (anaphylactic shock)

The frequency of some side effects cannot be estimated from available data

  • Fungal infections of the skin and mucous membranes (thrush)

New cases of inflammatory bowel disease or "flare-ups" can happen with COSENTYX, and can sometimes be serious. If you have inflammatory bowel disease (ulcerative colitis or Crohn's disease), tell your doctor if you have worsening symptoms during treatment with COSENTYX or develop new symptoms of stomach pain or diarrhoea.

COSENTYX may affect the results of some blood tests, including:

  • slight increase in blood cholesterol and blood fat (triglycerides)
  • elevated liver enzymes

In clinical trials, major adverse cardiovascular events were rarely observed with COSENTYX.

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

Tell your doctor if you notice anything else that is making you feel unwell. Other side effects not listed here or not yet known may happen in some people.

After taking COSENTYX

Storage

If you have to store COSENTYX:

  • Keep it in a refrigerator at 2°C to 8°C out of the sight and reach of children
  • Do not freeze it
  • Store it in the carton in order to protect it from light.
  • If necessary, COSENTYX can be left out of the refrigerator for a single period of up to 4 days at room temperature, not above 30°C. Do not put back in the refrigerator after it has reached room temperature. Discard any unused product.

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

A locked section of the refrigerator, at least one-and-a-half metres above the ground, is a good place to store COSENTYX.

Disposal

If your doctor tells you to stop taking this medicine or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Product description

What it looks like

COSENTYX solution for injection is a clear liquid. Its colour may vary from colourless to slightly yellow.

COSENTYX is available in packs containing 1 or 2 single-use pre-filled pens.

Ingredients

Each COSENTYX pre-filled pen contains 150 mg secukinumab as the active substance.

The other ingredients are:

  • trehalose dihydrate
  • histidine
  • histidine hydrochloride monohydrate
  • methionine
  • polysorbate 80
  • water for injection.

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

Sponsor

COSENTYX is supplied in Australia by:

Novartis Pharmaceuticals Australia Pty Limited
ABN 18 004 244 160
54 Waterloo Road
Macquarie Park NSW 2113
Telephone 1 800 671 203

® = Registered Trademark

This leaflet was prepared in May 2020.

Australian Registration Numbers:
Pre-filled pen AUST R 218800

(cos010520c based on PI cos010520i)

Published by MIMS June 2020

BRAND INFORMATION

Brand name

Cosentyx

Active ingredient

Secukinumab

Schedule

S4

 

1 Name of Medicine

Secukinumab (rch).
Chemical name: recombinant human monoclonal anti-human interleukin-17A (IL-17A, IL-17) antibody of the IgG1/kappa isotype.

6.7 Physicochemical Properties

Chemical structure.

The amino acid sequences of the light chain (215 amino acids) and the heavy chain (457 amino acids) respectively.
Molecular formula: C6584H10134N1754O2042S44.
Molecular weight: Approximately 148 kDa.

CAS number.

875356-43-7 (heavy chain), 875356-44-8 (light chain).

2 Qualitative and Quantitative Composition

Secukinumab is a recombinant fully human monoclonal antibody selective for interleukin-17A. Secukinumab is of the IgG1/κ-class produced in Chinese Hamster Ovary (CHO) cells.

3 Pharmaceutical Form

Powder for injection.

Each vial of powder for injection contains 150 mg of secukinumab as a lyophilised cake in glass vials.

Solution for injection.

Solution for injection in a single-use, pre-filled syringe and/or pen (auto-injector) containing 150 mg/mL of secukinumab.

5 Pharmacological Properties

Pharmacotherapeutic group: interleukin inhibitors; ATC Code: L04AC10.

5.1 Pharmacodynamic Properties

Serum levels of total IL-17A (free and secukinumab bound IL-17A) are increased due to reduced clearance of secukinumab bound IL-17A within 2 to 7 days in patients receiving secukinumab, indicating that secukinumab selectively captures free IL-17A which plays a key role in the pathogenesis of plaque psoriasis.
In a study with secukinumab, infiltrating epidermal neutrophils and various neutrophil associated markers that are increased in lesional skin of plaque psoriasis patients were significantly reduced after one to two weeks of treatment.
Secukinumab has been shown to lower (within 1 to 2 weeks of treatment) levels of C-reactive protein, which is a marker of inflammation in psoriatic arthritis and ankylosing spondylitis.

Mechanism of action.

Secukinumab is a fully human IgG1 antibody that selectively binds to and neutralises the proinflammatory cytokine interleukin-17A (IL-17A). IL-17A is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. IL-17A plays a key role in the pathogenesis of plaque psoriasis, psoriatic arthritis and ankylosing spondylitis. Increased numbers of IL-17A producing lymphocytes and innate immune cells and increased levels of IL-17A have been found in the blood of patients with plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis and affected skin of patients with plaque psoriasis. IL-17A is highly upregulated in lesional skin in contrast to nonlesional skin of plaque psoriasis patients. Higher frequency of IL-17 producing cells was detected in the synovial fluid of patients with psoriatic arthritis and in the subchondral bone marrow of facet joints from patients with ankylosing spondylitis. IL-17A also promotes tissue inflammation, neutrophil infiltration, bone and tissue destruction, and tissue remodelling including angiogenesis and fibrosis.
Secukinumab works by targeting IL-17A and inhibiting its interaction with the IL-17 receptor, which is expressed on various cell types including keratinocytes. As a result, secukinumab inhibits the release of proinflammatory cytokines, chemokines and mediators of tissue damage and reduces IL-17A mediated contributions to autoimmune and inflammatory diseases. Clinically relevant levels of secukinumab reach the skin and reduce local inflammatory markers. As a direct consequence, treatment with secukinumab reduces erythema, induration, and desquamation present in plaque psoriasis lesions.

Clinical trials.

Plaque psoriasis.

The safety and efficacy of Cosentyx were evaluated versus placebo or etanercept in four randomised, double blind, placebo controlled phase 3 studies in adult patients with moderate to severe chronic plaque type psoriasis poorly controlled by topical treatments and/or phototherapy and/or previous systemic therapy (ERASURE, FIXTURE, FEATURE, and JUNCTURE). The safety and efficacy of Cosentyx were evaluated versus placebo or etanercept in four randomised, double blind, placebo controlled phase 3 studies in patients with moderate to severe plaque psoriasis who were candidates for phototherapy or systemic therapy (ERASURE, FIXTURE, FEATURE, and JUNCTURE). In addition, one study assessed a chronic treatment regimen versus a 'retreatment as needed' regimen (SCULPTURE). The coprimary endpoints in the placebo and active controlled studies were the proportion of patients who achieved a PASI 75 response and IGA mod 2011 'clear' or 'almost clear' response versus placebo at week 12.
Key exclusion criteria across pivotal trials were: forms of psoriasis other than chronic plaque type; drug induced psoriasis; ongoing use of certain psoriasis treatments, e.g. topical or systemic corticosteroids or UV therapy; patients with active, ongoing inflammatory disease; patients with active, ongoing, chronic or recurrent infectious disease; evidence of tuberculosis infection (enrolment was allowed for patients with latent tuberculosis if appropriate treatment was initiated and maintained according to the local treatment guideline); history of HIV, hepatitis B or hepatitis C; underlying immunocompromising conditions; presence of lymphoproliferative disease, malignancy or history of malignancy within the past 5 years; significant medical problems including uncontrolled hypertension and congestive heart failure (NYHA class III and IV); patients with serum creatinine > 176.8 micromol/L or with white blood cell count < 2,500/microL, platelets < 100,000/microL, neutrophils < 1,500/microL or haemoglobin < 8.5 g/dL; pregnant or nursing women; and women of childbearing potential not using effective contraception during the study.
Of the 2,403 patients who were included in the placebo controlled studies, 79% were biologic naïve, 45% were nonbiologic failures, 8% were biologic failures, 6% were anti-TNF failures, and 2% were anti-p40 failures. Baseline disease characteristics were generally consistent across all treatment groups with a median baseline Psoriasis Area Severity Index (PASI) score from 19 to 20, IGA mod 2011 baseline score ranged from "moderate" (62%) to "severe" (38%), median baseline body surface area (BSA) ≥ 27 and median Dermatology Life Quality Index (DLQI) score from 10 to 12. Approximately 15 to 25% of patients in phase III studies had psoriatic arthritis (PsA) at baseline.

ERASURE study (A2302).

This trial evaluated 738 patients. Patients were randomised to Cosentyx received 150 mg or 300 mg doses at weeks 0, 1, 2, 3, and 4 followed by the same dose every month. Patients were randomised to receive placebo who were nonresponders at week 12 were then crossed over to receive Cosentyx (either 150 mg or 300 mg) at weeks 12, 13, 14, and 15, followed by the same dose every month starting at week 16. All patients were followed for up to 52 weeks following first administration of study treatment.

FIXTURE study (A2303).

This trial evaluated 1,306 patients. Patients were randomised to Cosentyx received 150 mg or 300 mg doses at weeks 0, 1, 2, 3, and 4 followed by the same dose every month. Patients were randomised to etanercept received 50 mg doses twice per week for 12 weeks followed by 50 mg every week. Patients were randomised to receive placebo who were nonresponders at week 12 then crossed over to receive Cosentyx (either 150 mg or 300 mg) at weeks 12, 13, 14, and 15, followed by the same dose every month starting at week 16. All patients were followed for up to 52 weeks following first administration of study treatment.

FEATURE study (A2308).

This trial evaluated 177 patients using a pre-filled syringe compared with placebo after 12 weeks of treatment to assess the safety, tolerability, and usability of Cosentyx self administration via the pre-filled syringe. Patients randomised to Cosentyx received 150 mg or 300 mg doses at weeks 0, 1, 2, 3, and 4 followed by the same dose every month. Patients were also randomised to receive placebo at weeks 0, 1, 2, 3, and 4 followed by the same dose every month.

JUNCTURE study (A2309).

This trial evaluated 182 patients using a pre-filled pen compared with placebo after 12 weeks of treatment to assess the safety, tolerability, and usability of Cosentyx self administration via the prefilled pen. Patients were randomised to Cosentyx received 150 mg or 300 mg doses at weeks 0, 1, 2, and 3, followed by the same dose every month starting at week 4. Patients were also randomised to receive placebo at weeks 0, 1, 2, and 3, followed by the same dose every month starting at week 4.

SCULPTURE study (A2304).

This trial evaluated 966 patients. All patients received Cosentyx 150 mg or 300 mg doses at weeks 0, 1, 2, 3, 4, 8 and 12 and then were randomised to receive either a maintenance regimen of the same dose every month starting at week 12 or a "retreatment as needed" regimen of the same dose.

Results.

The 300 mg dose provided improved skin clearance across efficacy endpoints of PASI 75/90/100, and IGA mod 2011 'clear' or 'almost clear' responses across all studies with peak effects seen at week 16 (see Table 5 and Table 6). Therefore the 300 mg dose is recommended.
Cosentyx was efficacious in biologic naive, biologic/ anti-TNF exposed and biologic/ anti-TNF failure patients.
Cosentyx was associated with a fast onset of efficacy as shown in Figure 1 with a 50% reduction in mean PASI by week 3 for 300 mg.
An additional psoriasis study (CLEAR) evaluated 676 patients. Secukinumab 300 mg met the primary and secondary endpoints by showing superiority to ustekinumab based on PASI 90 response at week 16 and speed of onset of PASI 75 response at week 4, and long term PASI 90 response at Week 52. Greater efficacy of secukinumab compared to ustekinumab for the endpoints PASI 75/90/100 and IGA mod 2011 0 or 1 response ("clear" or "almost clear") was observed early and continued through to week 52. See Table 7.
All plaque psoriasis phase III studies included approximately 15 to 25% of patients with concurrent psoriatic arthritis at baseline. Improvements in PASI 75 in this patient population were similar to those in the overall plaque psoriasis population.
In the subset of psoriatic arthritis patients in the ERASURE and FIXTURE studies, physical function was assessed using the HAQ Disability Index (HAQ-DI). In these studies, patients treated with 150 mg or 300 mg Cosentyx showed greater improvement from baseline in the HAQ-DI score (mean decreases of -27.5% and -50.2% at week 12) compared to placebo (-8.9%). This improvement was maintained up to week 52.
Patients in the SCULPTURE study that were randomised after week 12 to a "retreatment as needed" maintenance regimen did not achieve adequate maintenance of response to either dose used. After 52 weeks of treatment patients with 300 mg "retreatment as needed" regimen achieved a PASI 75 of 41.0% and a PASI 90 of 13.8%, whereas patients with a monthly maintenance regimen of 300 mg achieved a PASI 75 of 78.2% and a PASI 90 of 59.7%. Similarly, patients with 150 mg "retreatment as needed" regimen achieved a PASI 75 of 35.0% and a PASI 90 of 11.2%, whereas patients with a monthly maintenance regimen of 150 mg achieved a PASI 75 of 62.1% and a PASI 90 of 45.8% after 52 weeks of treatment. Therefore a fixed monthly maintenance regimen is recommended.

Specific locations/forms of plaque psoriasis.

In two additional placebo controlled studies, improvement was seen in both nail psoriasis (TRANSFIGURE, 198 patients) and palmoplantar plaque psoriasis (GESTURE, 205 patients). In the TRANSFIGURE study, secukinumab was superior to placebo at week 16 (46.1% for 300 mg, 38.4% for 150 mg and 11.7% for placebo) as assessed by significant improvement from baseline in the Nail Psoriasis Severity Index (NAPSI %) for patients with moderate to severe plaque psoriasis with nail involvement. In the GESTURE study, secukinumab was superior to placebo at week 16 (33.3% for 300 mg, 22.1% for 150 mg, and 1.5% for placebo) as assessed by significant improvement of the Palmoplantar Investigator's Global Assessment (ppIGA) 0 or 1 response ("clear" or "almost clear") for patients with moderate to severe palmoplantar plaque psoriasis.
The placebo-controlled SCALP study evaluated 102 patients with moderate to severe scalp psoriasis, defined as having a Psoriasis Scalp Severity Index (PSSI) score of ≥ 12, an IGA mod 2011 scalp only score of 3 or greater and at least 30% of the scalp surface area affected. In this study, 62% of patients had at least 50% of the scalp surface area affected. Secukinumab 300 mg was superior to placebo at Week 12 as assessed by significant improvement from baseline in both the PSSI 90 response (52.9% vs. 2.0%) and IGA mod 2011 0 or 1 scalp only response (56.9% vs. 5.9%). Greater efficacy of secukinumab 300 mg over placebo for both endpoints was observed by Week 3. Improvement in both endpoints was sustained for secukinumab patients who continued treatment through to Week 24 (PSSI 90 response 58.8% and IGA mod 2011 0 or 1 scalp only response 62.7%).

Quality of life/patient reported outcomes.

Statistically significant improvements at week 12 (studies 1-4) from baseline compared to placebo were demonstrated in the DLQI (Dermatology Life Quality Index), these improvements were maintained for 52 weeks (studies 1 and 2).
Statistically significant improvements at week 12 from baseline compared to placebo (ERASURE and FIXTURE studies) in patient reported signs and symptoms of itching, pain and scaling were demonstrated in the validated Psoriasis Symptom Diary.
Statistically significant improvements at Week 4 from baseline in patients treated with secukinumab compared to patients treated with ustekinumab (CLEAR) were demonstrated in the DLQI, and these improvements were maintained for up to 52 weeks. The Work Productivity and Activity Impairment Questionnaire-Psoriasis outcomes (WPAI-PSO) showed generally greater improvement in patients treated with secukinumab compared to patients treated with ustekinumab.
Statistically significant improvements in patient reported signs and symptoms of itching, pain and scaling at Week 16 and Week 52 (CLEAR) were demonstrated in the Psoriasis Symptom Diary in patients treated with secukinumab compared to patients treated with ustekinumab.
Statistically significant improvements at Week 12 from baseline compared to placebo (SCALP) were demonstrated in Health Related Quality of Life as measured by Scalpdex. These improvements were observed starting at Week 4 and were maintained through to Week 24.
Statistically significant improvements (decreases) at Week 12 from baseline (SCALP) were demonstrated in patient-reported signs and symptoms of scalp itching, pain, and scaling, compared to placebo.

Psoriatic arthritis.

The safety and efficacy of Cosentyx were assessed in 1,999 patients in three randomised, double-blind, placebo-controlled phase III studies in patients with active psoriatic arthritis (≥ 3 swollen and ≥ 3 tender joints) despite non-steroidal anti-inflammatory drug (NSAID), corticosteroids or disease-modifying anti-rheumatic drug (DMARD) therapy. Patients with each subtype of PsA were enrolled in these studies, including polyarticular arthritis with no evidence of rheumatoid nodules, spondylitis with peripheral arthritis, asymmetric peripheral arthritis, distal interphalangeal involvement and arthritis mutilans. Patients in these studies had a diagnosis of PsA for a median of 3.9 to 5.3 years. Approximately half of all enrolled patients had at least 3% BSA involvement with skin psoriasis at baseline. Over 61% and 42% of the PsA patients had enthesitis and dactylitis at baseline, respectively.
In FUTURE 1 Study (PsA1 Study), FUTURE 2 Study (PsA2 Study), and FUTURE 5 Study (PsA3 Study), 29%, 35%, and 30% of patients, respectively, were previously treated with an anti-TNF-alpha agent and discontinued the anti-TNF-alpha agent for either lack of efficacy or intolerance (anti-TNF-alpha-IR patients). For FUTURE 1 and FUTURE 2, the primary endpoint was American College of Rheumatology (ACR) 20 response at Week 24. The primary endpoint for FUTURE 5 was ACR 20 response at Week 16, and the key secondary endpoint was the change from baseline in modified Total Sharp Score (mTSS) at Week 24.
Key exclusion criteria across pivotal trials were: use of high potency opioid analgesics; ongoing use of certain psoriasis treatments, e.g. topical or systemic corticosteroids or UV therapy; previous exposure to secukinumab or any other biologic drugs for psoriasis and PsA except for those targeting TNFα, patients with active, ongoing inflammatory disease other than PsA; patients with active, ongoing, chronic or recurrent infectious disease; evidence of tuberculosis infection (enrolment was allowed for patients with latent tuberculosis if appropriate treatment was initiated and maintained according to the local treatment guideline); history of HIV, hepatitis B or hepatitis C; underlying immunocompromising conditions; presence of lymphoproliferative disease, malignancy or history of malignancy within the past 5 years; significant medical problems including uncontrolled hypertension and congestive heart failure (NYHA class III and IV); patients with serum creatinine > 132.6 micromol/L or with white blood cell count < 3,000/microL, platelets < 100,000/microL, neutrophils < 1,500/microL or haemoglobin < 8.5 g/dL; pregnant or nursing women; and women of childbearing potential not using effective contraception during the study.

FUTURE 1 study (F2306).

PsA1 study evaluated 606 patients, of whom 60.7% had concomitant MTX. Patients randomised to Cosentyx received 10 mg/kg, i.v. at weeks 0, 2, and 4, followed by either 75 mg or 150 mg s.c. every month starting at week 8. Patients randomised to receive placebo who were nonresponders at week 16 (early rescue) and other placebo patients at week 24 were crossed over to receive Cosentyx (either 75 mg or 150 mg) at week 16 followed by the same dose every month.

FUTURE 2 study (F2312).

PsA2 study evaluated 397 patients, of whom 46.6% had concomitant MTX. Patients randomised to Cosentyx received 75 mg, 150 mg or 300 mg s.c. at weeks 0, 1, 2, 3, and 4 followed by the same dose every month. Patients randomised to receive placebo who were nonresponders at week 16 (early rescue) were then crossed over to receive Cosentyx (either 150 mg or 300 mg, s.c.) at week 16 followed by the same dose every month. Patients randomised to receive placebo who were responders at week 16 were crossed over to receive Cosentyx (either 150 mg or 300 mg) at week 24 followed by the same dose every month.

FUTURE 5 study (F2342).

PsA3 Study evaluated 996 patients, of whom 50.1% had concomitant MTX treatment. Patients were randomised to receive Cosentyx 150 mg, 300 mg, or placebo s.c. at Weeks 0, 1, 2, 3 and 4 followed by the same dose every month, or a once monthly injection of Cosentyx 150 mg (without loading). Patients randomised to receive placebo who were non-responders at Week 16 were then crossed over to receive Cosentyx (either 150 mg or 300 mg, s.c.) at Week 16 followed by the same dose every month. Patients randomised to receive placebo who were responders at Week 16 were crossed over to receive Cosentyx (either 150 mg or 300 mg) at Week 24 followed by the same dose every month. The total combined duration of treatment for PsA3 Study is 2 years.

Signs and symptoms.

Treatment with Cosentyx resulted in significant improvement in the measure of disease activity compared to placebo at Weeks 16 and 24. (See Table 8).
The onset of action of Cosentyx occurred as early as week 2. Statistically significant difference in ACR 20 vs placebo was reached at week 3. In PsA2 efficacy responses were maintained up to Week 104. At week 16, Cosentyx treated patients demonstrated significant improvements in signs and symptoms among which significantly higher responses in ACR 20 (60.0% and 57.0% for 150 mg and 300 mg, respectively) compared to placebo (18.4%).
The percentage of patients achieving ACR 20 response by visit is shown in Figure 2.
Similar responses for primary and key secondary endpoints were seen in PsA patients regardless of whether they were on concomitant MTX treatment or not.
Both, anti-TNF-alpha-naïve and anti-TNF-alpha-IR Cosentyx treated patients, had a significantly higher ACR 20 response compared to placebo at week 24, with a slightly higher response in the anti-TNF-alpha-naïve group in the PsA2 study (anti-TNF-alpha-naïve: 64% and 58% for 150 mg and 300 mg, respectively, compared to placebo 15.9%; anti-TNF-alpha-IR: 30% and 46% for 150 mg and 300 mg, respectively, compared to placebo 14.3%). Anti-TNF-alpha-IR patients on 300 mg showed higher response rates on ACR 20 compared to placebo patients (p < 0.05) and demonstrated clinical meaningful benefit over 150 mg on multiple secondary endpoints. Improvements in the PASI 75 response were seen in both subgroups and the 300 mg dose showed statistically significant benefit in the anti-TNF-alpha-IR patients.
Improvements were shown in all components of the ACR scores, including patient assessment of pain. The proportion of patients achieving a modified PsA Response Criteria (PsARC) response was greater in the Cosentyx treated patients (59.0% and 61.0% for 150 mg and 300 mg, respectively) compared to placebo (26.5%) at week 24.
In PsA study 1 and PsA study 2, efficacy was maintained up to week 52. In PsA study 2, among 200 patients initially randomised to Cosentyx 150 mg and 300 mg, 178 (89%) patients were still on treatment at week 52. Of the 100 patients randomised to Cosentyx 150 mg, 64, 39 and 20 had an ACR 20/50/70 response, respectively. Of the 100 patients randomised to Cosentyx 300 mg, 64, 44 and 24 had an ACR 20/50/70 response, respectively.

Radiographic response.

In PsA3 Study, inhibition of progression of structural damage was assessed radiographically and expressed by the modified Total Sharp Score (mTSS) and its components, the Erosion Score (ES) and the Joint Space Narrowing Score (JSN). Radiographs of hands, wrists, and feet were obtained at baseline Week 16 and/or Week 24 and scored independently by at least two readers who were blinded to treatment group and visit number.
Cosentyx 150 mg and 300 mg treatment significantly inhibited the rate of progression of peripheral joint damage compared with placebo treatment as measured by change from baseline in mTSS at Week 24 (Table 9).
The percentage of patients with no disease progression (defined as a change from baseline in mTSS of ≤ 0.5) from randomisation to Week 24 was 80.3%, 88.5% and 73.6% for Cosentyx 150 mg, 300 mg and placebo, respectively. An effect of inhibition of structural damage was observed irrespective of concomitant MTX use or TNF status.
Structural damage was also assessed in the PsA1 Study. Radiographs of hands, wrists, and feet were obtained at baseline and Week 24 during the double-blind period when patients were on Cosentyx or placebo and at Week 52 when all patients were on open-label Cosentyx.
By Week 24, Cosentyx 150 mg treatment significantly inhibited the rate of progression of peripheral joint damage compared with placebo treatment as measured by change from baseline in mTSS (see Table 9). Inhibition of structural damage was maintained with Cosentyx treatment up to Week 52.
In PsA study 1, the inhibition of progression of structural damage was assessed radiographically and expressed as the change in modified Total Sharp Score (mTSS) and its components, the Erosion Score (ES) and the Joint Space Narrowing score (JSN) at weeks 24 and 52, compared to baseline. Week 24 data presented in Table 9.
Inhibition of structural damage was maintained with Cosentyx 150 mg treatment up to Week 104 in PsA Study 2 and with Cosentyx 300 mg treatment up to week 52 in PsA Study 3.
The percentage of patients with no-disease progression (defined as a change from baseline in mTSS of ≤ 0.5) from randomisation to Week 24 was, 82.3% in secukinumab 10 mg/kg i.v. load - 150 mg s.c. maintenance and 75.7% in placebo. The percentage of patients with no-disease progression, from Week 24 to Week 52, for the same above described regimen, was 85.7% and 86.8%, respectively.

Physical function and health related quality of life.

In PsA2 and PsA3 Studies, patients treated with Cosentyx 150 mg and 300 mg showed improvement in physical function compared to patients treated with placebo as assessed by change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 24 and Week 16, respectively. In PsA3 study, the change from baseline in HAQ-DI was -0.44 and -0.55 for Cosentyx 150 mg and 300 mg, respectively, versus -0.21 for placebo (< 0.0001). Improvements in HAQ-DI scores were seen regardless of previous anti-TNF-alpha exposure.
Cosentyx-treated patients reported significant improvements in health-related quality of life as measured by the Short Form (36) Health Survey Physical Component Summary (SF 36 PCS) score (p < 0.001) and these improvements were maintained up to Week 104 in PsA2.

Ankylosing spondylitis.

The safety and efficacy of Cosentyx were assessed in 816 patients in three randomised, double blind, placebo controlled phase III studies in patients with active ankylosing spondylitis (AS) with a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4 despite nonsteroidal anti-inflammatory drug (NSAID), corticosteroid or disease modifying antirheumatic drug (DMARD) therapy. Patients in the AS1 study and AS2 study had a diagnosis of AS for a median of 2.7 to 5.8 years.
In MEASURE 1 study (AS1 study), MEASURE 2 study (AS2 study), and MEASURE 3 study (AS3 study), 27.0%, 38.8%, and 23.5% of patients, respectively, were previously treated with an anti-TNF-alpha agent and discontinued the anti-TNFα agent for either lack of efficacy or intolerance (anti-TNF-alpha-IR patients).
Key exclusion criteria across pivotal trials were: patients with total ankylosis of the spine; use of high potency opioid analgesics; previous exposure to secukinumab or any other biologic drugs except for those targeting TNF-alpha, patients with active, ongoing inflammatory disease, other than AS; patients with active, ongoing, chronic or recurrent infectious disease; evidence of tuberculosis infection (enrolment was allowed for patients with latent tuberculosis if appropriate treatment was initiated and maintained according to the local treatment guideline); history of HIV, hepatitis B or hepatitis C; underlying immunocompromising conditions; presence of lymphoproliferative disease, malignancy or history of malignancy within the past 5 years; significant medical problems including uncontrolled hypertension and congestive heart failure (NYHA class III and IV); patients with serum creatinine > 132.6 micromol/L or with white blood cell count < 3,000/microL, platelets < 100,000/microL, neutrophils < 1,500/microL or haemoglobin < 8.5 g/dL; pregnant or nursing women; and women of childbearing potential not using effective contraception during the study.
AS1 study evaluated 371 patients, of whom 14.8% and 33.4% used concomitant MTX or sulfasalazine, respectively. Patients randomised to Cosentyx received 10 mg/kg, i.v. at weeks 0, 2, and 4, followed by either 75 mg or 150 mg s.c. every month starting at week 8. Patients randomised to placebo who were nonresponders at week 16 (early rescue) and all other placebo patients at week 24 were crossed over to receive Cosentyx (either 75 mg or 150 mg s.c.), followed by the same dose every month. The primary endpoint was at least a 20% improvement in Assessment of Spondyloarthritis International Society (ASAS 20) criteria at Week 16.
AS2 study evaluated 219 patients, of whom 11.9% and 14.2% used concomitant MTX or sulfasalazine, respectively. Patients randomised to Cosentyx received 75 mg or 150 mg s.c. at weeks 0, 1, 2, 3, and 4 followed by the same dose every month. At week 16, patients who were randomised to placebo at baseline were re-randomised to receive Cosentyx (either 75 mg or 150 mg) s.c. every month. The primary endpoint was ASAS 20 at Week 16.
AS3 study evaluated 226 patients, of whom 13.3% and 23.5% used concomitant MTX or sulfasalazine, respectively. Patients randomised to Cosentyx received 10 mg/kg, i.v. at Weeks 0, 2, and 4, followed by either 150 mg or 300 mg s.c. every month. At Week 16, patients who were randomised to placebo at baseline were re-randomised to receive Cosentyx (either 150 mg or 300 mg) s.c. every month. The primary end point was ASAS20 at Week 16. Patients were blinded to the treatment regimen up to Week 52, and the study continued to Week 156.

Signs and symptoms.

In AS2 study, treatment with Cosentyx 150 mg resulted in greater improvement in measures of disease activity compared with placebo at week 16 (see Table 10).
The onset of action of Cosentyx 150 mg occurred as early as week 1 for ASAS 20 and week 2 for ASAS 40 (superior to placebo) in AS2 study. (See Figures 3 and 4).
ASAS 20 responses were improved at week 16 in both anti-TNFα naïve patients (68.2% vs. 31.1%; p < 0.05) and anti-TNFα-IR patients (50.0% vs. 24.1%; p < 0.05) for Cosentyx 150 mg compared with placebo, respectively.
In AS1 study and AS2 study, Cosentyx treated patients (150 mg in AS2 study and both regimens in AS1 study) demonstrated significantly improved signs and symptoms at week 16, with comparable magnitude of response and efficacy was maintained up to week 52 in both anti-TNF-alpha-naïve and anti-TNF-alpha-IR patients. In AS study 2, among 72 patients initially randomised to Cosentyx 150 mg, 61 (84.7%) patients were still on treatment at week 52. Of the 72 patients randomised to Cosentyx 150 mg, 45 and 35 had ASAS 20/40 response, respectively.
In AS3 study, Cosentyx treated patients (150 mg and 300 mg) demonstrated improved signs and symptoms, and had comparable efficacy responses regardless of dose that were superior to placebo at Week 16 for the primary endpoint (ASAS20). Greater response rates favouring 300 mg were also observed for ASAS partial remission (ASAS PR) response at week 16. During the blinded period, the ASAS20 and ASAS40 responses were 69.7% and 47.6% for 150 mg and 74.3% and 57.4% for 300 mg at Week 52, respectively. The ASAS20 and ASAS40 responses were maintained through Week 156 (69.5% and 47.6% for 150 mg vs. 74.8% and 55.6% for 300 mg). The ASAS partial remission (ASAS PR) responses were 9.5% and 21.1% for 150 mg and 300 mg respectively, compared to 1.3% for placebo at Week 16. The ASAS PR responses were 18.1% and 24.3% for 150 mg and 300 mg at Week 52, respectively. These responses were maintained through Week 156 (15.1% for 150 mg and 27.2% for 300 mg).

Spinal mobility.

Patients treated with Cosentyx 150 mg showed improvements in spinal mobility as measured by change from baseline in BASMI at week 16 for both AS study 1 (0.40 versus 0.12 for placebo; (p = 0.0114) and AS study 2 (0.51 versus 0.22 for placebo; p = 0.0533). These improvements were sustained up to week 52.

Physical function and health related quality of life.

In AS study 1 and 2, patients treated with Cosentyx 150 mg showed improvements in health related quality of life as measured by ASQoL (p = 0.001) and SF-36 PCS (p < 0.001). These improvements were sustained up to week 52.
Patients treated with Cosentyx 150 mg also showed improvements on exploratory endpoints in physical function as assessed by the Bath Ankylosing Spondylitis Functional Index (BASFI) compared to placebo (-2.15 versus -0.68).

Non-clinical safety data.

Non-clinical data revealed no special hazard for humans based on tissue cross-reactivity testing, safety pharmacology, repeated dose and reproductive toxicity studies performed with secukinumab or a murine anti-murine IL-17A antibody.
Since secukinumab binds to cynomolgus monkey and human IL-17A, its safety was studied in the cynomolgus monkey. No undesirable effects of secukinumab were seen following subcutaneous administration to cynomolgus monkeys for up to 13 weeks and intravenous administration up to 26 weeks (including pharmacokinetic, pharmacodynamic, immunogenicity and immunotoxicity (e.g. T cell dependent antibody response and NK cell activity) evaluations). The average serum concentrations observed in monkeys after 13 weekly subcutaneous doses of 150 mg/kg are 48-fold higher than the predicted average serum concentration expected in psoriatic patients at the highest clinical dose. The exposure multiples are even higher when the average serum concentration from the 26 weeks intravenous toxicology study in cynomolgus monkeys are taken into consideration. Antibodies to secukinumab were detected in only one out of 101 animals. No non-specific tissue cross-reactivity was demonstrated when secukinumab was applied to normal human tissues.
No undesirable effects of a murine anti-murine IL-17A antibody were seen in fertility and early embryonic development and pre-and postnatal development studies in mice. The high dose used in these studies was in excess of the maximally effective dose in terms of IL-17A suppression and activity (see Section 4.6 Fertility, Pregnancy and Lactation).

5.2 Pharmacokinetic Properties

The mean pharmacokinetic parameters of secukinumab following single and multiple subcutaneous administration in adult patients with psoriasis, resulting from population pharmacokinetic analysis, are shown in Table 11. Cmax and AUC were dose proportional at 150 mg and 300 mg subcutaneous doses.

Pharmacokinetics in special patient groups.

Paediatrics (< 18 years of age).

Specific studies of Cosentyx in paediatric patients have not been conducted.

Elderly patients.

Of the 3,430 plaque psoriasis patients exposed to Cosentyx in clinical studies, a total of 230 were 65 years of age or older and 32 patients were 75 years of age or older.
Of the 2,536 psoriatic arthritis patients exposed to Cosentyx in clinical studies, a total of 236 patients were 65 years of age or older and 25 patients were 75 years of age or older.
Of the 794 ankylosing spondylitis patients exposed to Cosentyx in clinical studies, a total of 29 patients were 65 years of age or older and 3 patients were 75 years of age or older.
Based on population PK analysis, clearance in elderly patients and patients less than 65 years of age was similar.

Patients with renal and hepatic impairment.

No pharmacokinetic data are available in patients with hepatic or renal impairment.

Effect of weight on pharmacokinetics.

Secukinumab clearance and volume of distribution increase as bodyweight increases.

Absorption.

Following a single subcutaneous dose of either 150 mg or 300 mg in plaque psoriasis patients, secukinumab reached peak serum concentrations of 13.7 ± 4.8 microgram/mL or 27.3 ± 9.5 microgram/mL, respectively, between 5 to 6 days postdose.
After the initial weekly dosing during the first month, the time to reach the maximum concentration was between 31 and 34 days.
Peak concentrations at steady state (Cmax,ss) following subcutaneous administration of 150 mg or 300 mg were 27.6 microgram/mL and 55.2 microgram/mL, respectively. Steady state is reached after 20 weeks with monthly dosing regimens.
Compared with exposure after a single dose, patients exhibited a 2-fold increase in peak serum concentrations and AUC following repeated monthly dosing during maintenance.
Secukinumab is absorbed with an average absolute bioavailability of 73%.

Distribution.

The mean volume of distribution during the terminal phase (Vz) following a single intravenous administration ranged from 7.10 to 8.60 L in plaque psoriasis patients suggesting that secukinumab undergoes limited distribution to peripheral compartments.
Secukinumab concentrations in interstitial fluid in the skin of plaque psoriasis patients ranged from 28% to 39% of those in serum at 1 and 2 weeks after a single subcutaneous dose of 300 mg secukinumab.

Metabolism.

The metabolic pathway of secukinumab has not been characterised. As a human IgG1κ monoclonal antibody secukinumab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG.

Excretion.

Mean systemic clearance (CL) was 0.19 L/d in plaque psoriasis patients. Clearance was dose and time independent, as expected for a therapeutic IgG1 monoclonal antibody interacting with a soluble cytokine target, such as IL-17A.
The mean elimination half-life was estimated to be 27 days in plaque psoriasis patients. Estimated half-lives in individual plaque psoriasis patients range from 17 to 41 days.

Dose linearity.

The single and multiple dose pharmacokinetics of secukinumab in plaque psoriasis patients were determined in several studies with intravenous doses ranging from 1 x 0.3 mg/kg to 3 x 10 mg/kg and with subcutaneous doses ranging from 1 x 25 mg to multiple doses of 300 mg. Exposure was dose proportional across all dosing regimens.
The pharmacokinetics properties of secukinumab observed in psoriatic arthritis and ankylosing spondylitis patients were similar to those displayed in plaque psoriasis patients. The bioavailability of secukinumab in PsA patients was 85% on the basis of the population pharmacokinetic model.

5.3 Preclinical Safety Data

Genotoxicity.

Cosentyx has not been evaluated for genotoxic potential.

Carcinogenicity.

Secukinumab has not been evaluated for carcinogenic potential.

4 Clinical Particulars

4.1 Therapeutic Indications

Plaque psoriasis.

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

Psoriatic arthritis.

Cosentyx is indicated for the treatment of adult patients with active psoriatic arthritis when the response to previous disease-modifying anti-rheumatic drug (DMARD) therapy has been inadequate.

Ankylosing spondylitis.

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

4.3 Contraindications

Severe hypersensitivity reactions to the active substance or to any of the excipients (see Section 6.1 List of Excipients; Section 4.8 Adverse Effects (Undesirable Effects)).
Clinically important, active infections (see Section 4.4 Special Warnings and Precautions for Use).

4.4 Special Warnings and Precautions for Use

Infections.

Cosentyx has the potential to increase the risk of infections. In clinical studies, infections have been observed in patients receiving Cosentyx (see Section 4.8 Adverse Effects (Undesirable Effects)). Most of these were mild or moderate.
Related to the mechanism of action of Cosentyx, nonserious mucocutaneous candida infections were more frequently reported for secukinumab than placebo in the psoriasis clinical studies (3.55 per 100 patient years for secukinumab 300 mg versus 1.00 per 100 patient years for placebo) (see Section 4.8 Adverse Effects (Undesirable Effects)).
A similar increase in risk of infection was seen in placebo controlled trials in patients with psoriatic arthritis and ankylosing spondylitis. The incidence of some types of infections appeared to be dose dependent in clinical studies (see Section 4.8 Adverse Effects (Undesirable Effects)).
Caution should be exercised when considering the use of Cosentyx in patients with a chronic infection or a history of recurrent infection.
Patients should be instructed to seek medical advice if signs or symptoms suggestive of an infection occur. If a patient develops a serious infection, the patient should be closely monitored and Cosentyx should not be administered until the infection resolves.
No increased susceptibility to tuberculosis was reported from clinical studies. However, Cosentyx should not be given to patients with active tuberculosis. Antituberculosis therapy should be considered prior to initiation of Cosentyx in patients with latent tuberculosis.

Crohn's disease.

Caution should be exercised, when prescribing Cosentyx to patients with inflammatory bowel disease. Exacerbations, in some cases serious, occurred in Cosentyx treated patients during clinical trials in plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis. In addition, new onset inflammatory bowel disease cases occurred in clinical trials with Cosentyx.
Patients who are treated with Cosentyx should be monitored for signs and symptoms of inflammatory bowel disease.

Hypersensitivity reactions.

In clinical studies, rare cases of anaphylactic reactions have been observed in patients receiving Cosentyx. If an anaphylactic or other serious allergic reaction occurs, administration of Cosentyx should be discontinued immediately and appropriate therapy initiated.

Latex sensitive individuals - prefilled syringe/pen only.

The removable cap of the Cosentyx pre-filled syringe/pen contains a derivative of natural rubber latex. Although no natural rubber latex is detected in the cap, the safe use of Cosentyx pre-filled syringe/pen in latex sensitive individuals has not been studied.

Vaccinations.

Live vaccines should not be given concurrently with Cosentyx (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Patients treated with Cosentyx may receive vaccinations, except for live vaccines. In a study, after meningococcal and inactivated influenza vaccinations, a similar proportion of Cosentyx treated and placebo treated patients were able to mount an adequate immune response of at least a 4-fold increase in antibody titres to meningococcal or influenza vaccines. The data suggest that Cosentyx does not suppress the humoral immune response to the meningococcal and influenza vaccines.
Patients receiving Cosentyx may receive concurrent inactivated or nonlive vaccinations.

Use in hepatic impairment.

No data are available in patients with hepatic impairment.

Use in renal impairment.

No data are available in patients with renal impairment.

Use in the elderly.

Based on population PK analysis, clearance in patients aged 65 and older (n = 230) and patients less than 65 years of age was similar.

Paediatric use.

Safety and effectiveness in patients below the age of 18 years have not yet been established.

Effects on laboratory tests.

There is no known interference between Cosentyx and routine laboratory tests.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Live vaccines should not be given concurrently with Cosentyx (also see Section 4.4 Special Warnings and Precautions for Use).
In a study in subjects with plaque psoriasis, no clinically relevant pharmacokinetic interaction was observed between secukinumab and midazolam (CYP 3A4 substrate). Following initiation or discontinuation and during ongoing use of secukinumab in patients being treated with CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect or drug concentration and consider dosage adjustment as needed.
No interaction was seen when Cosentyx was administered concomitantly with methotrexate (MTX) and/or corticosteroids in arthritis studies (including in patients with psoriatic arthritis and ankylosing spondylitis).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

There are no special recommendations for females of reproductive potential.
The effect of Cosentyx on human fertility has not been evaluated. Animal studies do not indicate direct or indirect harmful effects with respect to fertility.
Fertility was unaffected in mice treated with an anti-murine IL17-A antibody.
(Category C)
There are no adequate data from the use of Cosentyx in pregnant women. Secukinumab was shown to cross the placenta in monkeys. Use of secukinumab during pregnancy may compromise the immunity of the fetus and neonate.
In an embryofetal development study in cynomolgus monkeys, secukinumab showed no maternal toxicity, embryofetal toxicity or teratogenicity when administered throughout organogenesis and late gestation at up to 150 mg/kg/week.
Cosentyx should be used in pregnancy only if the benefits clearly outweigh the potential risks.
If secukinumab has been used during pregnancy, administration of live vaccines to newborns/ infants for 16 weeks after the mother's last dose of secukinumab is generally not recommended.
It is not known whether secukinumab is excreted in human milk. Because immunoglobulins are excreted in human milk, caution should be exercised when Cosentyx is administered to a woman who is breastfeeding and a decision on whether to discontinue breastfeeding during treatment should be made.

4.8 Adverse Effects (Undesirable Effects)

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 www.tga.gov.au/reporting-problems.

Summary of the safety profile.

A total of 17,942 patients have been treated with Cosentyx in blinded and open-label clinical studies in various indications (plaque psoriasis and other autoimmune conditions), representing 29,978 patient years of exposure. Of these, over 11,752 patients were exposed to Cosentyx for at least one year.

Adverse reactions in plaque psoriasis.

Four placebo controlled phase III studies in plaque psoriasis were pooled to evaluate the safety of Cosentyx in comparison to placebo up to 12 weeks after treatment initiation. In total, 2,076 patients were evaluated (692 patients on 150 mg, 690 patients on 300 mg and 694 patients on placebo).
The most frequently reported adverse drug reactions (ADRs) were upper respiratory tract infections (most frequently nasopharyngitis, rhinitis). Most of the events were mild or moderate in severity.
In the placebo controlled period of plaque psoriasis phase III studies the proportion of patients who discontinued treatment due to adverse events was approximately 1.2% in the Cosentyx arm and 1.2% in the placebo arm. The adverse reactions from clinical studies (Table 1 and Table 2) are listed by MedDRA system organ class. Within each system organ class, the ADRs are ranked by frequency. Within each frequency grouping, adverse drug reactions are presented in order of decreasing seriousness. In addition, the corresponding frequency category for each adverse drug reaction is based on the following convention: very common (> 1/10); common (> 1/100, ≤ 1/10); uncommon (> 1/1,000, ≤ 1/100); rare (≥ 1/10,000, ≤ 1/1,000); very rare (< 1/10,000).
Adverse reactions that occurred at less than 1% frequency in the placebo controlled period of the ERASURE, FIXTURE, FEATURE and JUNCTURE studies through week 12 are given in Table 3.

Adverse drug reactions from spontaneous reports and literature cases (frequency not known).

The following adverse drug reactions have been derived from post-marketing experience with Cosentyx via spontaneous case reports and literature cases. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency which is therefore categorised as not known. Adverse drug reactions are listed according to system organ classes in MedDRA. Within each system organ class, ADRs are presented in order of decreasing seriousness. See Table 4.

Infections.

In the placebo controlled period of clinical studies in plaque psoriasis (a total of 1,382 patients treated with Cosentyx and 694 patients treated with placebo for up to 12 weeks), infections were reported in 28.7% of patients treated with Cosentyx compared with 18.9% of patients treated with placebo. Most of these were mild or moderate. Serious infections occurred in 0.14% of patients treated with Cosentyx and in 0.3% of patients treated with placebo (see Section 4.4 Special Warnings and Precautions for Use).
Over the entire treatment period (a total of 3,430 patients treated with Cosentyx for up to 52 weeks for the majority of patients), infections were reported in 47.5% of patients treated with Cosentyx (0.9 per patient year of follow-up). Serious infections were reported in 1.2% of patients treated with Cosentyx (0.015 per patient year of follow-up).
There was an increase in mucosal or cutaneous candidiasis, related to the mechanism of action. The cases were mild or moderate in severity, nonserious, responsive to standard treatment and did not necessitate treatment discontinuation. Frequency of candida infection was 1.2% (secukinumab 300 mg) vs 0.3% (placebo and etanercept arms) in the induction period.
Infection rates as observed in psoriatic arthritis and ankylosing spondylitis clinical studies were similar to what was observed in the psoriasis studies.

Neutropenia.

In psoriasis phase 3 clinical studies, neutropenia was more frequently observed with secukinumab than with placebo, but most cases were mild, transient and reversible. Neutropenia < 1.0-0.5 x 109/L (CTCAE grade 3) was reported in 18 out of 3,430 (0.5%) patients on secukinumab, with no dose dependence and no temporal relationship to infections in 15 out of 18 cases. There were no reported cases of more severe neutropenia. Nonserious infections with usual response to standard care and not requiring discontinuation of Cosentyx were reported in the remaining 3 cases.
The frequency of neutropenia in psoriatic arthritis and ankylosing spondylitis is similar to psoriasis.
Rare cases of neutropenia < 0.5 x 109/L (CTCAE grade 4) were reported.

Hypersensitivity reactions.

In clinical studies, urticaria and rare case of anaphylactic reaction to Cosentyx were observed.

Immunogenicity.

In psoriasis, psoriatic arthritis and ankylosing spondylitis clinical studies less than 1% of patients treated with Cosentyx developed antibodies to secukinumab up to 52 weeks of treatment. About half of the treatment emergent antidrug antibodies were neutralising, but this was not associated with loss of efficacy or PK abnormalities.

Reproductive system related adverse events.

In the induction period of clinical studies, mild and moderate reproductive system adverse events were reported in females, including: dysmenorrhoea (secukinumab 300 mg, 1.9%; placebo, 0.5%; etanercept, 1.1%), menorrhagia (secukinumab 300 mg, 0.9%; placebo, 0%; etanercept, 0%) and metrorrhagia (including menometrorrhagia) (secukinumab 300 mg, 1.4%; placebo, 0%; etanercept, 0%). Women of childbearing potential were included in studies only if using adequate contraception.

Major adverse cardiovascular events (MACE).

In the secukinumab clinical trials, MACE events were observed in patients receiving secukinumab. In the phase 3 studies in psoriasis, PsA and AS, the exposure adjusted incidence rates of adjudication confirmed MACE cases per 100 patient years was 0.49 (19/3911.6 patient years, 95% CI 0.29, 0.76) for secukinumab versus 0.00 (0/351.3 patient years, 95% CI 0.00, 1.05) for placebo. In the overall secukinumab program, the exposure adjusted incidence rates of adjudication confirmed cases per 100 patient years for secukinumab was 0.40 (25/6259.8 patient years, 95% CI 0.26, 0.59) versus 0.39 (2/515.1 patient years, 95% CI 0.05, 1.40) for placebo.

Adverse reactions in psoriatic arthritis.

Cosentyx was studied in five placebo-controlled psoriatic arthritis trials with 2,754 patients (1,871 patients on Cosentyx and 883 patients on placebo) with a total exposure of 4,478 patient-years of study exposure on Cosentyx. The adverse events that occurred at a proportion of at least 2% and at a higher proportion in the Cosentyx groups than the placebo groups during the 16-week placebo-controlled period were nasopharyngitis, upper respiratory tract infection, headache, urinary tract infection, and hypercholesterolemia. The safety profile observed in patients with psoriatic arthritis treated with Cosentyx is consistent with the safety profile in psoriasis.
The proportion of patients with infections in the Cosentyx groups (28.5%) is similar to the placebo group (28.1%) (see Section 4.4 Special Warnings and Precautions for Use).
There were cases of Crohn's disease and ulcerative colitis that include patients who experienced either exacerbations or the development of new disease. In the psoriatic arthritis program with 2,536 patients exposed to Cosentyx there were 17 cases of inflammatory bowel disease during the entire treatment period (0.4 per 100 patient-years). During the placebo-controlled period 16 week period, there were seven cases of inflammatory bowel disease, of which five patients received secukinumab and two received placebo (see Section 4.4 Special Warnings and Precautions for Use).

Cholesterol and triglycerides.

CTCAE grade 1 and grade 2 elevations of blood cholesterol and triglyceride levels were reported in patients receiving secukinumab compared to placebo in psoriatic arthritis clinical trials.
The elevations of cholesterol levels were limited primarily to CTCAE grade 1 (28.7% vs. 19.1%, respectively) and grade 2 (1.6% vs. 0.5%, respectively). No cases of CTCAE grade 3 and grade 4 cholesterol levels were observed in either secukinumab or placebo groups during the placebo controlled period.
An increase in blood triglycerides levels was also observed in psoriatic arthritic patients receiving secukinumab compared to placebo (CTCAE Grade 1: 26.7% vs. 19.1%, Grade 2: 4.6% vs. 3.5%, Grade 3: 1.0% vs. 0.7% and Grade 4: 0.2% vs. 0.1%, respectively) up to Week 16.
Elevations (mainly CTCAE grade 1 and grade 2) in cholesterol and triglycerides were also observed during long-term treatment with secukinumab.

Hepatic transaminases.

During the placebo-controlled period, increased incidence of elevated hepatic transaminases was observed in psoriatic arthritis patients treated with secukinumab compared to placebo. The elevations in hepatic transaminases were seen primarily in CTCAE Grade 1 (ALT: 17.1% vs 14.8%; AST: 12.5% vs. 10.1%, respectively). No difference in the incidence of elevated ALT and AST was seen between secukinumab and placebo in CTCAE Grade 2, Grade 3 and Grade 4. No cases of CTCAE Grade 4 were observed for AST.
Elevations (mainly CTCAE grade 1 and grade 2) in ALT and AST was also observed during the long-term treatment with secukinumab.

Adverse reactions in ankylosing spondylitis.

Cosentyx was studied in three placebo controlled ankylosing spondylitis trials with 816 patients (544 patients on Cosentyx and 272 patients on placebo). The median duration of exposure for secukinumab treated patients was 469 days in AS1 study, 460 days in AS2 study, and 1,142 days in AS3 study. During the 16 week placebo controlled period of the trials in patients with ankylosing spondylitis, the overall proportion of patients with adverse events was higher in the secukinumab groups than the placebo treatment groups (60% and 55%, respectively).
The overall safety profile of Cosentyx in AS3 study remained in line with the safety profile established in the pivotal AS1 and AS2 studies, which are summarised in the next paragraphs.
The adverse events that occurred at a proportion of at least 2% and at a higher proportion in the Cosentyx groups than the placebo groups during the 16 week placebo controlled period were nasopharyngitis, nausea, and upper respiratory tract infection. The safety profile observed in patients with ankylosing spondylitis treated with Cosentyx is consistent with the safety profile in psoriasis.
Similar to clinical trials in patients with psoriasis, there was an increased proportion of patients with infections in the Cosentyx groups (31%) compared to the placebo group (18%) (see Section 4.4 Special Warnings and Precautions for Use).
In the ankylosing spondylitis program, with 571 patients exposed to Cosentyx there were 8 cases of inflammatory bowel disease during the entire treatment period (5 Crohn's (0.7 per 100 patient years) and 3 ulcerative colitis (0.4 per 100 patient years)). During the placebo controlled 16 week period, there were 2 Crohn's disease exacerbations and 1 new onset ulcerative colitis case that was a serious adverse event in patients treated with Cosentyx compared to none of the patients treated with placebo. During the remainder of the study when all patients received Cosentyx, 1 patient developed Crohn's disease, 2 patients had Crohn's exacerbations, 1 patient developed ulcerative colitis, and 1 patient had an ulcerative colitis exacerbation (see Section 4.4 Special Warnings and Precautions for Use).

Cholesterol and triglycerides.

CTCAE grade 1 and grade 2 elevations of blood cholesterol and triglyceride levels were reported in patients receiving secukinumab compared to placebo in ankylosing spondylitis clinical trials.
The elevations of cholesterol levels were limited primarily to CTCAE grade 1 (20.0% vs. 19.8%, respectively). Increase in CTCAE grade 2 cholesterol levels was uncommon (0.8% vs. 0.0%, respectively) and no cases of CTCAE grade 3 and grade 4 cholesterol levels were observed in both secukinumab and placebo groups during the placebo controlled period.
An increase in blood triglycerides levels was also observed in ankylosing spondylitis patients receiving secukinumab or placebo (CTCAE grade 1: 17.8% vs. 17.1%, grade 2: 2.7% vs. 2.7%, and grade 3: 0.8% vs. 0.5%, respectively). No cases of CTCAE grade 4 triglyceride levels were reported during the placebo controlled period.
Elevations (mainly CTCAE grade 1 and grade 2) in cholesterol and triglycerides were also observed during long-term treatment with secukinumab.

Hepatic transaminases.

During the placebo controlled period, increased incidence of elevated hepatic transaminases was observed in ankylosing spondylitis patients treated with secukinumab compared to placebo. The elevations in hepatic transaminases were seen primarily in CTCAE grade 1 (ALT: 16.6% vs. 7.1%; AST: 11.3% vs. 7.0%, respectively). Increase in CTCAE grade 2 and grade 3 hepatic transaminase levels was uncommon in both secukinumab and placebo groups (grade 2 ALT: 1.0% vs. 0.5%, AST: 0.5% vs. 0.0%; grade 3 ALT: 0.8% vs. 0.0%, AST: 0.8% vs.1.6%, respectively). One case of CTCAE grade 4 ALT levels was reported in the placebo group and no cases of CTCAE grade 4 ALT and AST levels were reported in the secukinumab group.
Elevations (mainly CTCAE grade 1 and grade 2) in ALT and AST was also observed during the long-term treatment with secukinumab.

4.2 Dose and Method of Administration

Dosage.

Plaque psoriasis.

The recommended dose is 300 mg by subcutaneous injection with initial dosing at weeks 0, 1, 2, 3, and 4 followed by the same dose every month. Each 300 mg dose is given as two subcutaneous injections of 150 mg.

Psoriatic arthritis.

The recommended dose is 150 mg by subcutaneous injection with initial dosing at Weeks 0, 1, 2, 3, and 4 followed by the same dose every month. Based on clinical response, the dose can be increased to 300 mg.
For patients who are anti-TNF-alpha inadequate responders (IR) or patients with concomitant moderate to severe plaque psoriasis, the recommended dose is 300 mg by subcutaneous injection with initial dosing at Weeks 0, 1, 2, 3, and 4 followed by the same dose every month. Each 300 mg dose is given as two subcutaneous injections of 150 mg.
Cosentyx may be administered with or without methotrexate.

Ankylosing spondylitis.

The recommended dose is 150 mg by subcutaneous injection with initial dosing at Weeks 0, 1, 2, 3, and 4 followed by the same dose every month. Based on clinical response, the dose can be increased to 300 mg.
Each 300 mg dose is given as two subcutaneous injections of 150 mg.

Assessment prior to initiation of Cosentyx.

Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with Cosentyx (see Section 4.4 Special Warnings and Precautions for Use).

Special populations.

Patients with renal or hepatic impairment.

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

Paediatric and adolescent patients.

Safety and effectiveness in patients below the age of 18 years have not yet been established.

Elderly patients (≥ 65 years of age).

No dose adjustment is needed for elderly patients.

Administration.

The product is for single use in one patient only. Discard any residue.

Powder for injection.

Cosentyx is administered by subcutaneous injection. Each vial of Cosentyx must be reconstituted with 1 mL of sterile water for injections to obtain a 150 mg/mL solution. The powder for injection should be administered by healthcare professionals only.

Prefilled syringe and pre-filled pen.

Cosentyx is administered by subcutaneous injection. If possible, areas of the skin that show psoriasis should be avoided as injection sites.
Before injection, secukinumab may be allowed to reach room temperature (20 minutes) without removing the needle cap during this time.
Prior to administration, the liquid must be checked whether it is clear and colourless. The solution should not be used if discoloured, or cloudy, or if foreign particles are present.
After proper training in subcutaneous injection technique, patients or appropriate caregiver may self-inject Cosentyx if a physician determines that it is appropriate. However, the physician should ensure appropriate follow-up of patients. Patients should be instructed to inject the full amount of Cosentyx according to the instructions provided in the package leaflet. Comprehensive instructions for administration are given in the package leaflet.

4.7 Effects on Ability to Drive and Use Machines

No studies on the effects on the ability to drive and use of machines have been performed.

4.9 Overdose

No case of overdose has been reported in clinical studies.
Doses up to 30 mg/kg (i.e. approximately 2,000 mg to 3,000 mg) have been administered intravenously in clinical studies without dose limiting toxicity.
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 Poisons Information Centre on 13 11 26 (Australia).

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription medicine.

6 Pharmaceutical Particulars

6.1 List of Excipients

Powder for injection.

Water for injections, sucrose, histidine, histidine hydrochloride monohydrate, polysorbate 80.

Solution for injection.

Trehalose dihydrate, histidine, histidine hydrochloride monohydrate, polysorbate 80, methionine, water for injections.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

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

Powder for solution.

Store at 2-8°C. Store in the original package.

Prefilled syringe.

Store at 2-8°C. Do not freeze. Protect from light.
Store in the original package.
May be stored unrefrigerated (out of fridge) for a single period up to a maximum of 4 days at room temperature below 30°C. Do not put back in the refrigerator after it has reached room temperature. Discard any unused product.

Prefilled pen.

Store at 2-8°C. Do not freeze. Protect from light.
Store in the original package.
May be stored unrefrigerated (out of fridge) for a single period up to a maximum of 4 days at room temperature below 30°C. Do not put back in the refrigerator after it has reached room temperature. Discard any unused product.

6.5 Nature and Contents of Container

Powder for solution.

Secukinumab 150 mg as a sterile white solid lyophilisate for subcutaneous injection. Packs containing 1* or 2* single-use vials.

Prefilled syringe.

Secukinumab 150 mg/1 mL solution for subcutaneous injection in a single use pre-filled syringe (PFS). The sterile solution is colourless to slightly yellow. Packs containing 1* or 2* pre-filled syringes.

Prefilled pen.

Secukinumab 150 mg/1 mL solution for subcutaneous injection in a single use pre-filled pen. The sterile solution is colourless to slightly yellow. The pen consists of a PFS assembled into a pen with a removable rubber cap. Packs containing 1* or 2* pre-filled pens.
* Not all pack sizes or presentations may be marketed.

6.6 Special Precautions for Disposal

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

Summary Table of Changes