Cosentyx 75 mg/0.5 mL/150 mg/300 mg/2 mL Solution

Plaque psoriasis

COSENTYX u00ae is indicated for the treatment of moderate to severe plaque psoriasis in patients 6 years and older who are candidates for systemic therapy or phototherapy.

Psoriatic arthritis

COSENTYX u00ae is indicated for the treatment of adult patients with active psoriatic arthritis. COSENTYX u00ae can be used alone or in combination with methotrexate.

Axial spondyloarthritis (axSpA) with or without radiographic damage

Ankylosing spondylitis (AS)/axSpA with radiographic damage

COSENTYX u00ae is indicated for the treatment of adult patients with active ankylosing spondylitis.

Non-radiographic axial spondyloarthritis (nr-axSpA) / axSpA without radiographic damage

COSENTYX u00ae is indicated for the treatment of active non-radiographic axial spondyloarthritis with objective signs of inflammation as indicated by elevated C-reactive protein (CRP) and/or magnetic resonance imaging (MRI) evidence in adults who have responded inadequately to nonsteroidal anti-inflammatory drugs (NSAIDs).

Juvenile Idiopathic Arthritis (JIA)

Enthesitis-Related Arthritis (ERA)

COSENTYX u00ae is indicated for the treatment of active enthesitis-related arthritis in patients 2 years and older.

Juvenile Psoriatic Arthritis (JPsA)

COSENTYX u00ae is indicated for the treatment of active juvenile psoriatic arthritis in patients 2 years and older.

Hidradenitis Suppurativa (HS)

COSENTYX u00ae is indicated for the treatment of adult patients with moderate to severe hidradenitis suppurativa (acne inversa).

COSENTYX u00ae is intended for use under the guidance and supervision of a physician experienced in the diagnosis and treatment of conditions for which COSENTYX u00ae is indicated.

Posology

Adult plaque psoriasis

The recommended dose is 300 mg of secukinumab by subcutaneous injection with initial dosing at weeks 0, 1, 2, 3 and 4, followed by monthly maintenance dosing. Some patients may derive an additional benefit from receiving 300 mg every 2 weeks. Each 300 mg dose is given as one subcutaneous injection of 300 mg or as two subcutaneous injections of 150 mg.

Paediatric plaque psoriasis (adolescents and children from the age of 6 years)

The recommended dose is based on body weight (Table 1) and administered by subcutaneous injection with initial dosing at Weeks 0, 1, 2, 3, and 4 followed by monthly maintenance dosing (every 4 weeks). Each 75 mg dose is given as one subcutaneous injection of 75 mg. Each 150 mg dose is given as one subcutaneous injection of 150 mg. Each 300 mg dose is given as one subcutaneous injection of 300 mg or as two subcutaneous injections of 150 mg.

Table 1 Recommended dose of COSENTYX u00ae for paediatric plaque psoriasis

• Body weight at time of dosing
• Recommended Dose
• < 25 kg
• 75 mg
• 25 to < 50 kg
• 75 mg (*may be increased to 150 mg)
• u2265 50 kg
• 150 mg (*may be increased to 300 mg)

*Some patients may derive additional benefit from the higher dose. The 150 mg solution for injection in pre-filled syringe or pen is not indicated for administration to paediatric patients with a weight < 50 kg.

Psoriatic arthritis

For patients with concomitant moderate to severe plaque psoriasis or who are anti-TNFu03b1 inadequate responders (IR), the recommended dose is 300 mg by subcutaneous injection with initial dosing at weeks 0, 1, 2, 3 and 4, followed by monthly maintenance dosing. Each 300 mg dose is given as one subcutaneous injection of 300 mg or as two subcutaneous injections of 150 mg. For other patients, the recommended dose is 150 mg by subcutaneous injection with initial dosing at weeks 0, 1, 2, 3 and 4, followed by monthly maintenance dosing. Based on clinical response, the dose can be increased to 300 mg.

Axial spondyloarthritis (axSpA)

Ankylosing spondylitis (AS)

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

Non-radiographic axial spondyloarthritis (nr-axSpA)

The recommended dose is 150 mg by subcutaneous injection with initial dosing at weeks 0, 1, 2, 3, and 4 followed by monthly maintenance dosing.

For all of the above indications, available data suggest that a clinical response is usually achieved within 16 weeks of treatment. Consideration should be given to discontinuing treatment in patients who have shown no response by 16 weeks of treatment. Some patients with an initial partial response may subsequently improve with continued treatment beyond 16 weeks.

Juvenile Idiopathic Arthritis (JIA)

Enthesitis-Related Arthritis (ERA) and Juvenile Psoriatic Arthritis (JPsA)

The recommended dose is based on body weight. For patients weighing < 50 kg the dose is 75 mg. For patients weighing u2265 50 kg the dose is 150 mg. COSENTYX u00ae is administered by subcutaneous injection at Weeks 0, 1, 2, 3, and 4 followed by monthly maintenance dosing (every 4 weeks). Each 75 mg dose is given as one subcutaneous injection of 75 mg. Each 150 mg dose is given as one subcutaneous injection of 150 mg.

Hidradenitis Suppurativa

The recommended dose is 300 mg of secukinumab by subcutaneous injection with initial dosing at Weeks 0, 1, 2, 3 and 4, followed by a maintenance dose of 300 mg every 2 weeks. Each 300 mg dose is given as one subcutaneous injection of 300 mg or as two subcutaneous injections of 150 mg.

Special populations

Elderly patients (aged 65 years and over)

No dose adjustment is required (see section 5.2).

Renal impairment / hepatic impairment

COSENTYX u00ae has not been studied in these patient populations. No dose recommendations can be made.

Paediatric population

Safety and effectiveness in paediatric patients with the JIA categories of ERA and JPsA below the age of 2 years have not been established. The safety and efficacy of COSENTYX u00ae in children with plaque psoriasis below the age of 6 years have not been established. The safety and efficacy of COSENTYX u00ae in children below the age of 18 years in other indications have not yet been established. No data are available.

Method of administration

Pre-filled syringe and pre-filled pen: COSENTYX u00ae is to be administered by subcutaneous injection. If possible, areas of the skin that show psoriasis should be avoided as injection sites. The solution/the syringe/the pen must not be shaken. After proper training in subcutaneous injection technique, patients may self-inject COSENTYX u00ae or be injected by a caregiver if a physician determines that this is appropriate. However, the physician should ensure appropriate follow up of patients. Patients and/or caregivers should be instructed to inject the full amount of COSENTYX u00ae according to the instructions provided in the patient information leaflet. Comprehensive instructions for administration are given in the patient information leaflet. For patients receiving the 75 mg dose, the 75 mg/0.5 mL pre-filled syringe should be used.

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Clinically important, active infection, e.g., active tuberculosis (see section 4.4).

Live vaccines should not be given concurrently with COSENTYX u00ae (see section 4.5).

Pregnancy and lactation.

Traceability

In order to improve the traceability of biological medicines, the name and the batch number of the administered product should be clearly recorded.

Infections

Secukinumab has the potential to increase the risk of infections. Serious infections have been observed in patients receiving secukinumab in the post-marketing setting. Caution should be exercised when considering the use of secukinumab 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 secukinumab should not be administered until the infection resolves.

In clinical studies, infections have been observed in patients receiving secukinumab (see section 4.8). Most of these were mild or moderate upper respiratory tract infections such as nasopharyngitis and did not require treatment discontinuation.

Related to the mechanism of action of secukinumab, non-serious 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).

No increased susceptibility to tuberculosis was reported from clinical studies. However, secukinumab should not be given to patients with active tuberculosis. Anti-tuberculosis therapy should be considered prior to initiation of secukinumab in patients with latent tuberculosis or in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed. Patients receiving secukinumab should be regularly monitored for signs and symptoms of active tuberculosis during and after treatment.

Inflammatory bowel disease (IBD)

Cases of new or exacerbations of Crohnu2019s disease and ulcerative colitis have been reported (see section 4.8). Caution should be exercised when prescribing secukinumab to patients with inflammatory bowel disease, including Crohnu2019s disease and ulcerative colitis. In addition, cases of new onset IBD have been reported with post-marketing use. Patients should be closely monitored.

Hypersensitivity reactions

In clinical studies, rare cases of anaphylactic reactions and angioedema have been observed in patients receiving secukinumab. Angioedema cases have also been reported in the post-marketing setting. If an anaphylactic or other serious allergic reactions occur, administration of secukinumab should be discontinued immediately and appropriate therapy initiated.

Eczematous eruptions

In post-marketing reports, cases of severe eczematous eruptions, including dermatitis-like eruptions, dyshidrotic eczema, and erythroderma (exfoliative dermatitis), were reported in patients receiving COSENTYX u00ae; some cases resulted in hospitalization (see section 4.8). The onset of eczematous eruptions was variable, ranging from days to months after the first dose of COSENTYX u00ae. Treatment with COSENTYX u00ae may need to be discontinued to resolve the eczematous eruption. Some patients were successfully treated for eczematous eruptions while continuing COSENTYX u00ae.

Latex sensitive individuals u2013 1 mL pre-filled-syringe/pen and 0.5 mL pre-filled syringe

The removable needle caps of the COSENTYX u00ae 1 mL pre-filled syringe/pen and 0.5 mL pre-filled syringe, contain a derivative of natural rubber latex. No natural rubber latex has to date been detected in the removable needle cap. Nevertheless, the use of COSENTYX u00ae pre-filled syringes/pens in latex sensitive individuals has not been studied and there is therefore a potential risk of hypersensitivity reactions which cannot be completely ruled out.

Vaccinations

Live vaccines should not be given concurrently with secukinumab (see also section 4.4). Patients receiving secukinumab may receive concurrent inactivated or non-live vaccinations. In a study, after meningococcal and inactivated influenza vaccinations, a similar proportion of healthy volunteers treated with 150 mg of secukinumab and those treated with placebo were able to mount an adequate immune response of at least a 4-fold increase in antibody titres to meningococcal and influenza vaccines. The data suggests that secukinumab does not suppress the humoral immune response to the meningococcal or influenza vaccines. Prior to initiating therapy with COSENTYX u00ae, it is recommended that paediatric patients receive all age-appropriate immunisations as per current immunisation guidelines.

Concomitant immunosuppressive therapy

In psoriasis studies, the safety and efficacy of secukinumab in combination with immunosuppressants, including biologics, or phototherapy have not been evaluated. Secukinumab was administered concomitantly with methotrexate (MTX), sulfasalazine and/or corticosteroids in arthritis studies (including in patients with psoriatic arthritis and ankylosing spondylitis). Caution should be exercised when considering concomitant use of other immunosuppressants and secukinumab (see also section 4.5).

Live vaccines should not be given concurrently with secukinumab (see also section 4.4). In a study in adult subjects with plaque psoriasis, no interaction was observed between secukinumab and midazolam (CYP3A4 substrate). No interaction was seen when secukinumab was administered concomitantly with methotrexate (MTX) and/or corticosteroids in arthritis studies (including in patients with psoriatic arthritis and ankylosing spondylitis).

Women of childbearing potential

Women of childbearing potential should use an effective method of contraception during treatment and for at least 20 weeks after treatment.

Pregnancy

COSENTYX u00ae is contraindicated in pregnant women (see section 4.3).

Breast-feeding

Because immunoglobulins are excreted in milk, secukinumab should not be administered to a woman who is breastfeeding.

Fertility

The effect of secukinumab on human fertility has not been evaluated. Animal studies do not indicate direct or indirect harmful effects with respect to fertility.

COSENTYX u00ae has no or negligible influence on the ability to drive and use machines.

Summary of the Safety Profile

The most frequently reported adverse drug reactions (ADRs) are upper respiratory tract infections (most frequently nasopharyngitis, rhinitis).

Tabulated list of adverse reactions

ADRs from clinical studies and post-marketing reports (Table 2) are listed by MedDRA system organ class. Within each system organ class, the ADRs are ranked by frequency, with the most frequent reactions first. 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 (u2265 1/10); common (u2265 1/100 to < 1/10); uncommon (u2265 1/1,000 to < 1/100); rare (u2265 1/10,000 to < 1/1,000); very rare (< 1/10,000); and not known (cannot be estimated from the available data). Over 20,000 patients have been treated with secukinumab in blinded and open-label clinical studies in various indications (plaque psoriasis and other autoimmune conditions), representing 34,908 patient years of exposure. Of these, over 14,000 patients were exposed to secukinumab for at least one year. The safety profile of secukinumab is consistent across all indications.

Table 2 List of adverse reactions in clinical studies and post-marketing experience

System Organ Class Frequency Adverse reaction

Infections and infestations Very common Upper respiratory tract infections

Common Oral herpes

Tinea pedis

Uncommon Oral candidiasis

Otitis externa

Lower respiratory tract infections

Not known Mucosal and cutaneous candidiasis (including oesophageal candidiasis)

Blood and lymphatic system disorders Uncommon Neutropenia

Immune system disorders Rare Anaphylactic reactions

Nervous system disorders Common Headache

Eye disorders Uncommon Conjunctivitis

Respiratory, thoracic and mediastinal disorders Common Rhinorrhoea

Gastrointestinal disorders Common Diarrhoea

Nausea

Uncommon Inflammatory bowel disease (including Crohnu2019s disease and ulcerative colitis).

Skin and subcutaneous tissue disorders Common Urticaria, Dermatitis (including eczema)

Uncommon Dyshidrotic eczema

Rare Exfoliative dermatitis

Not known Pyoderma gangrenosum, Dermatitis exfoliative generalized, angioedema

General disorders and administration site conditions Common Fatigue

1) Placebo-controlled clinical studies (phase III) in plaque psoriasis, PsA, AS and nr-axSpA patients exposed to 300 mg, 150 mg, 75 mg or placebo up to 12 weeks (psoriasis) or 16 weeks (PsA, AS and nr-axSpA) treatment duration 2) Cases were reported in patients with psoriasis diagnosis 3) Adverse Drug Reactions added based on post marketing reports. Frequency determined based on placebo-controlled clinical studies (phase III) in plaque psoriasis patients. 4) These events are related to Eczematous eruptions

Description of selected adverse reactions

Infections

In the placebo-controlled period of clinical studies in plaque psoriasis (a total of 1,382 patients treated with secukinumab and 694 patients treated with placebo for up to 12 weeks), infections were reported in 28,7 % of patients treated with secukinumab compared with 18,9 % of patients treated with placebo. The majority of infections consisted of non-serious and mild to moderate upper respiratory tract infections, such as nasopharyngitis, which did not necessitate treatment discontinuation. There was an increase in mucosal or cutaneous candidiasis, consistent with the mechanism of action, but the cases were mild or moderate in severity, non-serious, responsive to standard treatment and did not necessitate treatment discontinuation. Serious infections occurred in 0,14 % of patients treated with secukinumab and in 0,3 % of patients treated with placebo (see section 4.4).

Over the entire treatment period (a total of 3,430 patients treated with secukinumab for up to 52 weeks for the majority of patients), infections were reported in 47,5 % of patients treated with secukinumab (0,9 per patient-year of follow-up). Serious infections were reported in 1,2 % of patients treated with secukinumab (0,015 per patient-year of follow-up).

Infection rates observed in psoriatic arthritis and ankylosing spondylitis clinical studies were similar to those observed in the psoriasis studies. Due to the nature of the lesions, patients with hidradenitis suppurativa are more susceptible to infections. In the placebo-controlled period of clinical studies in hidradenitis suppurativa (a total of 721 patients treated with secukinumab and 363 patients treated with placebo for up to 16 weeks), infections were numerically higher to those observed in the psoriasis studies (30.7 % of patients treated with secukinumab compared with 31.7 % in patients treated with placebo). Most of these were non-serious, mild or moderate in severity and did not require treatment discontinuation or interruption.

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 10 9 /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. Non-serious infections with usual response to standard care and not requiring discontinuation of secukinumab 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 10 9 /l (CTCAE grade 4) were reported.

Hypersensitivity reactions

In clinical studies, urticaria, rare cases of anaphylactic reactions and angioedema have been observed in patients receiving COSENTYX u00ae. Angioedema cases have also been reported in the post-marketing setting. (see also section 4.4).

Immunogenicity

In psoriasis, psoriatic arthritis, axial spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis), and hidradenitis suppurativa clinical studies, less than 1 % of patients treated with secukinumab developed antibodies to secukinumab up to 52 weeks of treatment. About half of the treatment-emergent anti-drug antibodies were neutralising, but this was not associated with loss of efficacy or pharmacokinetic abnormalities.

Adverse reactions in hidradenitis suppurativa

COSENTYX u00ae was studied in two placebo-controlled hidradenitis suppurativa trials with 1,084 patients (721 patients on COSENTYX u00ae and 363 on placebo) with a total exposure of 825 patient years of study exposure (median duration of exposure for secukinumab-treated patients: 307 days). The safety profile observed in patients with HS treated with COSENTYX u00ae was consistent with the known safety profile observed in psoriasis.

Paediatric population

The safety of secukinumab was assessed in two phase III studies in paediatric patients with plaque psoriasis. The first study (paediatric study 1) was a double-blind, placebo-controlled study of 162 patients from 6 to less than 18 years of age with severe plaque psoriasis. The second study (paediatric study 2) is an open-label study of 84 patients from 6 to less than 18 years of age with moderate to severe plaque psoriasis. The safety profile reported in these two studies was consistent with the safety profile reported in adult plaque psoriasis patients.

The safety of COSENTYX u00ae was also assessed in a Phase III study in 86 paediatric patients from 2 to less than 18 years of age with the ERA and JPsA categories of JIA. The safety profile reported in this study was consistent with the safety profile reported in adult patients.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare providers are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8

Doses up to 30 mg/kg (approximately 2000 to 3000 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.