Scapho

Scapho

secukinumab

Manufacturer:

Novartis

Distributor:

Zuellig Pharma
Full Prescribing Info
Contents
Secukinumab.
Description
Active substance: Each vial of powder for solution for subcutaneous injection contains 150 mg of secukinumab when reconstituted with 1 mL water for injection.
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.
Excipients/Inactive Ingredients: Powder for solution for subcutaneous injection: Sucrose, L-histidine, L-histidine hydrochloride monohydrate, polysorbate 80, water for injection.
Action
Pharmacology: Pharmacodynamics: Mechanism of Action: Secukinumab is a fully human IgG1 antibody that selectively binds to and neutralizes the proinflammatory cytokine interleukin-17A (IL-17A). Secukinumab works by targeting IL-17A and inhibiting its interaction with the IL-17 receptor, which is expressed on various cell types including keratinocytes and synoviocytes. 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.
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 and psoriatic arthritis 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 affected skin of patients with plaque psoriasis. IL-17A is highly up-regulated in lesional skin in contrast to non-lesional skin of plaque psoriasis patients. Furthermore higher frequency of IL-17-producing cells was detected in the synovial fluid of patients with psoriatic arthritis. The frequency of IL-17 producing cells was also significantly higher 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 remodeling including angiogenesis and fibrosis.
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.
Clinical Studies: Psoriasis: The safety and efficacy of Scapho were assessed in four randomized, 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, JUNCTURE]. The efficacy and safety of Scapho 150 mg and 300 mg were evaluated versus either placebo or etanercept. In addition, one study assessed a chronic treatment regimen versus a 'retreatment as needed' regimen [SCULPTURE].
Of the 2,403 patients who were included in the placebo-controlled studies, 79% were biologic-naive, 45% were non-biologic 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.
Psoriasis Study 1 (ERASURE) evaluated 738 patients. Patients randomized to Scapho received 150 mg or 300 mg doses at weeks 0, 1, 2, and 3 and 4 followed by the same dose every month. Patients randomized to receive placebo who were non-responders at week 12 were then crossed over to receive Scapho (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.
Psoriasis Study 2 (FIXTURE) evaluated 1,306 patients. Patients randomized to Scapho received 150 mg or 300 mg doses at weeks 0, 1, 2, and 3 and 4 followed by the same dose every month. Patients randomized to etanercept received 50 mg doses twice per week for 12 weeks followed by 50 mg every week. Patients randomized to receive placebo who were non-responders at week 12 then crossed over to receive Scapho (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.
Psoriasis Study 3 (FEATURE) evaluated 177 patients using a pre-filled syringe compared with placebo after 12 weeks of treatment to assess the safety, tolerability, and usability of Scapho self-administration via the pre-filled syringe. Patients randomized to Scapho 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 randomized to receive placebo at weeks 0, 1, 2, and 3 and 4 followed by the same dose every month.
Psoriasis Study 4 (JUNCTURE) evaluated 182 patients using a pre-filled pen compared with placebo after 12 weeks of treatment to assess the safety, tolerability, and usability of Scapho self-administration via the pre-filled pen. Patients randomized to Scapho received 150 mg or 300 mg doses at weeks 0, 1, 2, and 3 and 4 followed by the same dose every month. Patients were also randomized to receive placebo at weeks 0, 1, 2, and 3, followed by the same dose every month.
Psoriasis Study 5 (SCULPTURE) evaluated 966 patients. All patients received Scapho 150 mg or 300 mg doses at weeks 0, 1, 2, 3, 4, 8 and 12 and then were randomized 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. Patients randomized to "retreatment as needed" did not achieve adequate maintenance of response and therefore a fixed monthly maintenance regimen is recommended.
The co-primary 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 (see Tables 1 and 2). 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, therefore this dose is recommended.

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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 (primary endpoint), 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 long-term PASI 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 Week 52. (See Table 3.)

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Scapho was efficacious in biologic-naive, biologic/anti-TNF-exposed and biologic/anti-TNF-failure patients.
Scapho was associated with a fast onset of efficacy as shown in the figure below with a 50% reduction in mean PASI by week 3 for 300 mg. (See Figure.)

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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 placebo controlled studies 1 and 2 in the subset of psoriatic arthritis patients, physical function was assessed using the HAQ Disability Index (HAQ-DI). In these studies, patients treated with 150 mg or 300 mg Scapho 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.
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 ppIGA 0 or 1 response ("clear" or "almost clear") for patients with moderate to severe palmoplantar 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 affected. In this study, 62% of patients had at least 50% or more of scalp surface area affected. Secukinumab 300 mg was superior to placebo at Week 12 as assessed by significant improvement from baseline in both the PASI 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 Week 24 (PASI 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 (Studies 1 and 2) 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 (Dermatology Life Quality Index), and these improvements were maintained for up to 52 weeks. The Work Productivity and Activity Impairment Questionnaire-Psoriasis outcomes (WPAI-PSO) showed 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 the HRQoL (Health Related Quality of Life Index) as measured by Scalpdex. These improvements were observed starting at Week 4 and were maintained through 24 weeks.
Statistically significant improvements (decreases) at week 12 from baseline (SCALP) were demonstrated in patient reported signs and symptoms of scalp itching (-59.4%), pain (-45.9%), and scaling (-69.5%), whereas placebo treated patients demonstrated worsening (increases) in scalp itching (7.7%) and pain (38.5%), and less improvement in scalp scaling (-4.7%).
Psoriatic arthritis: The safety and efficacy of Scapho were assessed in 1003 patients in two randomized, 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. Over 62% and 47% of the PsA patients had enthesitis and dactylitis at baseline, respectively.
The efficacy and safety of Scapho 75 mg, 150 mg and 300 mg were evaluated versus placebo with either an i.v. or s.c. loading dose regimen. In Psoriatic Arthritis 1 Study (PsA1 Study) and Psoriatic Arthritis 2 Study (PsA2 Study) 29% and 35% of patients, respectively, were previously treated with an anti-TNFα agent and discontinued the anti-TNFα agent for either lack of efficacy or intolerance (anti-TNFα-IR patients).
PsA1 Study (FUTURE 1) evaluated 606 patients, of whom 60.7% had concomitant MTX. Patients randomized to Scapho 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 randomized to receive placebo who were non-responders at Week 16 were then crossed over to receive Scapho (either 75 mg or 150 mg) at Week 16 followed by the same dose every month. Patients randomized to receive placebo who were responders at Week 16 were then crossed over to receive Scapho (either 75 mg or 150 mg) at Week 24 followed by the same dose every month. The primary endpoint was American College of Rheumatology (ACR) 20 response at Week 24.
PsA2 Study (FUTURE 2) evaluated 397 patients, of whom 46.6% had concomitant MTX. Patients randomized to Scapho received 75 mg, 150 mg or 300 mg s.c. at Weeks 0, 1, 2, and 3 and 4 followed by the same dose every month starting at Week 4. Patients randomized to receive placebo who were non-responders at Week 16 were then crossed over to receive Scapho (either 150 mg or 300 mg, s.c.) at Week 16 followed by the same dose every month. Patients randomized to receive placebo who were responders at Week 16 were crossed over to receive Scapho (either 150 mg or 300 mg) at Week 24 followed by the same dose every month. The primary endpoint was ACR 20 response at Week 24.
Clinical response: Signs and symptoms: Treatment with Scapho resulted in significant improvement in the measure of disease activity compared to placebo at Weeks 16 and 24 (see Table 4).

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The onset of action of Scapho occurred as early as Week 2. Statistically significant difference in ACR 20 vs placebo was reached at Week 3.
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-TNFα-naive and anti-TNFα-IR Scapho-treated patients, had a significantly higher ACR 20 response compared to placebo at Week 24 with a slightly higher response in the anti- TNFα- naive group (anti-TNFα-naive: 37%, 64% and 58% for 75 mg, 150 mg and 300 mg, respectively, compared to placebo 15.9%; anti-TNFα-IR: 15%, 30% and 46% for 75 mg, 150 mg and 300 mg, respectively, compared to placebo 14.3%). Anti-TNF & alpha-IR patients on 300mg showed higher response rates on ACR20 compared to placebo patients (p<0.05) and demonstrated clinical meaningful benefit over 150 mg on multiple secondary endpoints. Improvements in the PASI75 response were seen regardless of previous anti-TNFα exposure.
In PsA1 Study, Scapho-treated patients demonstrated significantly improved PsA signs and symptoms at Week 24 with similar magnitude of response to PsA2 Study. Efficacy was maintained up to Week 52.
Radiographic response: Structural damage was 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 Scapho or placebo and at Week 52 when all patients were on open-label Scapho. A modified Total Sharp Score (mTSS) was used to express the changes.
By Week 24, Scapho 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 5).

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Radiographic inhibition was observed in both anti-TNFα-naive and anti-TNFα-IR patients. Similar effect of inhibition of structural damage was observed irrespective of concomitant MTX use. Inhibition of structural damage was maintained with Scapho treatment up to Week 52.
The percentage of patients with no-disease progression (defined as a change from baseline in modified total Sharp score of ≤ 0.5) from randomization to Week 24 was 92.3% in secukinumab 10 mg/kg i.v. load-75 mg s.c. maintenance, 82.3% in secukinumab 10 mg/kg i.v. load-150 mg s.c. maintenance and 75.7% in placebo.
Physical function and health related quality of life: In PsA2 Study, patients treated with Scapho 150 mg and 300 mg showed improvement in physical function compared to patients treated with placebo as assessed by Heath Assessment Questionnaire-Disability Index (HAQ-DI) at Week 24. The proportion of patients on 150 mg or 300 mg who achieved a minimal clinically important difference (MCID) of ≥0.3 improvement in HAQ-DI score from baseline was greater compared to placebo at Week 24 (46.0%, 49.0% vs. 16.3%, p<0.0001).
There was greater improvement in Dermatology Life Quality Index (DLQI) scores in the Scapho groups as compared to placebo at Week 24 (p<0.01). There was also greater improvement in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scores in the 150 mg and 300 mg Scapho groups when compared to placebo at Week 24 (p<0.01). Scapho-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). Improvements were also seen for EQ-5D. In addition improvements were seen in the psoriatic arthritis QoL (PsAQoL p<0.01) and in psoriatic arthritis-related productivity at work and within household, as reported by the Work Productivity and Activity Impairment-General Health questionnaire (WPAI-GH) compared to placebo at Week 24.
In PsA1 Study, Scapho-treated patients significantly improved physical function as assessed by HAQ-DI and SF-36 Physical Components at Week 24. Efficacy was maintained up to Week 52.
Ankylosing spondylitis: The safety and efficacy of Scapho were assessed in 590 patients in two randomized, 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 these studies had a diagnosis of AS for a median of 2.7 to 5.8 years.
The efficacy and safety of Scapho 75 mg and 150 mg were evaluated versus placebo with either an i.v. or s.c. loading regimen. In Ankylosing Spondylitis 1 Study (AS1 Study) and Ankylosing Spondylitis 2 Study (AS2 Study) 27.0% and 38.8% of patients, respectively, were previously treated with an anti-TNFα agent and discontinued the anti-TNFα agent for either lack of efficacy or intolerance (anti-TNFα-IR patients).
AS1 Study (MEASURE 1) evaluated 371 patients, of whom 14.8% and 33.4% used concomitant MTX or sulfasalazine, respectively. Patients randomized to Scapho received 10 mg/kg, i.v., at Weeks 0, 2, and 4, followed by either 75 mg or 150 mg s.c. every month. Patients randomized to receive placebo who were non-responders at Week 16 were crossed over to receive Scapho (either 75 mg or 150 mg) at Week 16, followed by the same dose every month. Patients randomized to receive placebo who were responders at Week 16 were crossed over to receive Scapho (either 75 mg or 150 mg) at Week 24, followed by the same dose every month. The primary end point was at least a 20% improvement in Assessment of Spondyloarthritis International Society (ASAS20) criteria at Week 16.
AS2 Study (MEASURE 2) evaluated 219 patients, of whom 11.9% and 14.2% used concomitant MTX or sulfasalazine, respectively. Patients randomized to Scapho 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 randomized to placebo at baseline were re-randomized to receive Scapho (either 75 mg or 150 mg) s.c. every month. The primary end point was ASAS 20 at Week 16.
Clinical response: Signs and symptoms: In AS2 Study, treatment with Scapho 150 mg resulted in greater improvement in ASAS20, ASAS40, high-sensitivity C-reactive protein (hsCRP), ASAS 5/6 and BASDAI score compared with placebo at Week 16 (see Table 6).

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The onset of action of Scapho 150 mg occurred as early as Week 1 for ASAS20 (superior to placebo) in AS2 Study.
ASAS20 responses were improved at Week 16 in both antiTNFα-naïve patients (68.2% vs. 31.1%; p<0.05) and anti-TNFα-IR patients (50.0% vs. 24.1%; p<0.05) for Scapho 150 mg compared with placebo, respectively.
The magnitude of response (treatment difference versus placebo) with regards to signs and symptoms at Week 16 was similar in anti-TNFα-naïve and anti-TNFα-IR patients in both studies, with higher absolute response rates in anti-TNFα-naïve patients.
Physical function and health-related quality of life: In AS2 Study, patients treated with Scapho 150 mg showed improvements by Week 16 compared to placebo-treated patients in physical function as assessed by the BASFI (-2.15 vs 0.68, p< 0.0001) and in pain as assessed by the Total and Nocturnal Back Pain scale (-29.64 vs -9.64, p<0.0001). Scapho-treated patients reported improvements compared to placebo-treated patients in tiredness (fatigue) as reported at Week 16 by scores on the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale and in health-related quality of life as measured by ASQoL (LS mean change: -4.00 vs -1.37, p<0.001) and SF-36 Physical Component Summary (SF-36 PCS) (LS mean change: 6.06 vs 1.92, p< 0.001). Scapho 150 mg had numerically larger mean improvements than placebo for 3 of the 4 Work Productivity and Activity Impairment-General Health (WPAI-GH) outcomes at Week 16. These improvements were sustained up to Week 52.
In AS1 Study, Scapho-treated patients reported improvement in physical function compared to placebo-treated patients at Week 16, as assessed by the BASFI, Total and Nocturnal Back Pain scale, FACIT-Fatigue, ASQoL, EQ-5D and SF-36 Physical Component Summary. Numerically greater increases in work productivity as measured with the WPAI-GH were also observed at Week 16 (tests of significance not performed). These improvements in physical function were all sustained up to Week 52.
Pharmacokinetics: 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 μg/mL or 27.3 ± 9.5 μg/mL, respectively, between 5 and 6 days post dose.
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 μg/mL and 55.2 μg/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.
Elimination: 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 PK properties of secukinumab observed in psoriatic arthritis were similar to those displayed in plaque psoriasis patients.
Special populations: Elderly patients: Of the 3,430 plaque psoriasis patients exposed to Scapho 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 974 PsA patients exposed to Scapho in clinical studies, a total of 85 patients were 65 years of age or older and 4 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.
Toxicology: 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 intraveneous 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 redicted 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.
Animal studies have not been conducted to evaluate the carcinogenic potential of secukinumab.
In an embryofetal development study in cynomolgus monkeys, secukinumab showed no maternal toxicity, embryotoxicity or teratogenicity when administered throughout organogenesis and late gestation.
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 Use in Pregnancy & Lactation).
Indications/Uses
Plaque psoriasis: Scapho is indicated for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy.
Psoriatic arthritis: Scapho is indicated for the treatment of adult patients with active psoriatic arthritis. Scapho can be used alone or in combination with methotrexate.
Ankylosing spondylitis: Scapho is indicated for the treatment of adult patients with active ankylosing spondylitis.
Dosage/Direction for Use
Plaque psoriasis: The recommended dose is 300 mg by subcutaneous injection with initial dosing at weeks 0, 1, 2 and 3 and 4 followed by monthly maintenance dosing. 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 and 3 and 4 followed by monthly maintenance dosing.
For patients who are anti-TNFα 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 and 3 and 4 followed by monthly maintenance dosing starting at Week 4. Each 300 mg dose is given as two subcutaneous injections of 150 mg.
Ankylosing spondylitis: 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.
Special populations: Renal impairment/hepatic impairment: Scapho has not been studied specifically in these patient populations.
Pediatric patients: Safety and effectiveness in pediatric patients below the age of 18 years have not yet been established.
Geriatric patients (65 years of age or older): No dose adjustment is required.
Method of administration: Powder for solution for injection: Scapho is administered by subcutaneous injection. Scapho powder for solution must be reconstituted before use.
Full instructions for use are provided in Instructions for Use and Handling under Cautions for Usage.
Overdosage
No cases of overdose have been reported in clinical studies.
Doses up to 30 mg/kg (i.e. approximately 2,000 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.
Contraindications
Severe hypersensitivity reactions to the active substance or to any of the excipients (see Description, Precautions and Adverse Reactions).
Special Precautions
Infections: Scapho has the potential to increase the risk of infections. In clinical studies, infections have been observed in patients receiving Scapho (see Adverse Reactions). Most of these were mild or moderate.
Caution should be exercised when considering the use of Scapho 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 Scapho should not be administered until the infection resolves.
No increased susceptibility to tuberculosis was reported from clinical studies. However, Scapho should not be given to patients with active tuberculosis. Anti-tuberculosis therapy should be considered prior to initiation of Scapho in patients with latent tuberculosis.
Crohn's disease: Caution should be exercised, when prescribing Scapho to patients with active Crohn's disease as exacerbations of Crohn's disease, in some cases serious, were observed in clinical studies in both Scapho and placebo groups. Patients who are treated with Scapho and have active Crohn's disease should be followed closely.
Hypersensitivity reactions: In clinical studies, rare cases of anaphylactic reactions have been observed in patients receiving Scapho. If an anaphylactic or other serious allergic reaction occurs, administration of Scapho should be discontinued immediately and appropriate therapy initiated.
Vaccinations: Live vaccines should not be given concurrently with Scapho (see Interactions).
Patients receiving Scapho may receive concurrent inactivated or non-live vaccinations. In a study, after meningococcal and inactivated influenza vaccinations, a similar proportion of patients treated with Scapho and patients treated with placebo were able to mount an adequate immune response of at least a 4-fold increase in antibody titers to meningococcal and influenza vaccines. The data suggest that Scapho does not suppress the humoral immune response to the meningococcal or influenza vaccines.
Females and males of reproductive potential: Infertility: There are no special recommendations for females of reproductive potential.
The effect of Scapho on human fertility has not been evaluated. Animal studies do not indicate direct or indirect harmful effects with respect to fertility. (See Pharmacology: Toxicology: Non-Clinical Safety data under Actions.)
Use In Pregnancy & Lactation
Use in Pregnancy: Risk Summary: There are no adequate data from the use of Scapho in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonic/fetal development, parturition or postnatal development. Because animal reproduction studies are not always predictive of human response, Scapho should be used during pregnancy only if the benefits clearly outweigh the potential risks.
Animal Data: In an embrtofetal development study in cynomolgous monkeys, secukinumab showed no maternal toxicity, embryotoxicity or teratogenicity when administered throughout organogenesis and late gestation.
Use in Lactation: It is not known whether secukinumab is excreted in human milk. Because immunoglobulins are excreted in human milk, caution should be exercised when Scapho is administered to a woman who is breast-feeding.
Adverse Reactions
Summary of the safety profile: A total of 6,200 patients have been treated with Scapho in blinded and open-label clinical studies in various indications (plaque psoriasis and other autoimmune conditions), representing 6,267 patient years of exposure. Of these, 3,671 patients were exposed to Scapho 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 Scapho 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 Scapho arm and 1.2% in the placebo arm.
ADRs from clinical studies (Table 7) 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 (CIOMS III): very common (≥ 1/10); common (≥ 1/100 to <1/10); uncommon (≥ 1/1,000 to <1/100); rare (≥ 1/10,000 to <1/1,000); very rare (<1/10,000). (See Table 7.)

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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 Scapho 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 categorized 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 8.)

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Infections: In the placebo-controlled period of clinical studies in plaque psoriasis (a total of 1,382 patients treated with Scapho and 694 patients treated with placebo for up to 12 weeks), infections were reported in 28.7% of patients treated with Scapho 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 Scapho and in 0.3% of patients treated with placebo (see Precautions).
Over the entire treatment period (a total of 3,430 patients treated with Scapho for up to 52 weeks for the majority of patients), infections were reported in 47.5% of patients treated with Scapho (0.9 per patient-year of follow-up). Serious infections were reported in 1.2% of patients treated with Scapho (0.015 per patient-year of follow-up).
Infection rates as observed in psoriatic arthritis and ankylosing spondylitis clinical studies were similar to what was observed in the psoriasis studies.
Hypersensitivity reactions: In clinical studies, urticaria and rare cases of anaphylactic reactions to Scapho were observed.
Immunogenicity: In psoriasis and psoriatic arthritis clinical studies, less than 1% of patients treated with Scapho developed antibodies to secukinumab up to 52 weeks of treatment. About half of the treatment emergent anti-drug antibodies were neutralizing, but this was not associated with loss of efficacy or PK abnormalities.
Adverse reactions in psoriatic arthritis: Scapho was studied in two placebo-controlled psoriatic arthritis trials with 1,003 patients (703 patients on Scapho and 300 patients on placebo) for a total exposure of 1,061 patient- years of study exposure (median duration of exposure for secukinumab-treated patients: 456 days in PsA1 Study and 245 days in PsA2 Study). The safety profile observed in patients with psoriatic arthritis treated with Scapho is consistent with the safety profile in psoriasis.
Adverse reactions in ankylosing spondylitis: Scapho was studied in two placebo-controlled ankylosing spondylitis trials with 590 patients (394 patients on Scapho and 196 patients on placebo) for a total of 755 patient-years of study exposure (median duration of exposure for secukinumab-treated patients: 469 days in AS 1 Study and 460 days in AS 2 Study). The safety profile observed in patients with ankylosing spondylitis treated with Scapho is consistent with the safety profile in plaque psoriasis.
Drug Interactions
Live vaccines should not be given concurrently with Scapho (see Precautions).
In a study in subjects with plaque psoriasis, no interaction was observed between secukinumab and midazolam (CYP 3A4 substrate).
Scapho has been concomitantly administered with methotrexate (MTX) and/or corticosteroids in arthritis studies (including psoriatic arthritis and ankylosing spondylitis) where no interaction was seen.
Caution For Usage
Instructions for Use and Handling: Instruction for Use of Scapho 150 mg powder for solution for injection: The following information is intended for medical or healthcare professionals only.
Store the vial of 150 mg powder for solution for injection of Scapho in the refrigerator between 2°C to 8°C.
The single-use vial contains 150 mg of Scapho for reconstitution with sterile water for injection (SWFI). Do not use the vial after the expiry date shown on the outer box or vial. If it has expired, return the entire pack to the pharmacy.
The preparation of the solution for subcutaneous injection shall be done without interruption ensuring that aseptic technique is used. The preparation time from piercing the stopper until end of reconstitution on average takes 20 minutes and should not exceed 90 minutes.
To prepare Scapho 150 mg powder for solution for injection please adhere to the following instructions: Instructions for reconstitution of Scapho 150 mg powder for solution for injection: Bring the vial of Scapho 150 mg powder for solution for injection to room temperature and ensure sterile water for injection (SWFI) is at room temperature.
Withdraw slightly more than 1.0 mL sterile water for injection (SWFI) into a 1 mL graduated disposable syringe and adjust to 1.0 mL.
Remove the plastic cap from the vial.
Insert the syringe needle into the vial containing the lyophilized cake of Scapho through the center of the rubber stopper and reconstitute the cake by slowly injecting 1.0 mL of SWFI into the vial. The stream of SWFI should be directed onto the lyophilized cake.
Tilt the vial to an angle of approx. 45° and gently rotate between the fingertips for approx. 1 minute. Do not shake or invert the vial.
Keep the vial standing at room temperature for a minimum of 10 minutes to allow for dissolution. Note that foaming of the solution may occur.
Tilt the vial to an angle of approx. 45° and gently rotate between the fingertips for approx. 1 minute. Do not shake or invert the vial.
Allow the vial to stand undisturbed at room temperature for approximately 5 minutes. The resulting solution should be clear. Its color may vary from colorless to slightly yellow. Do not use if the lyophilized powder has not fully dissolved or if the liquid contains easily visible particles, is cloudy or is distinctly brown.
Prepare the required number of vials (1 vial for the 150 mg dose, 2 vials for the 300 mg dose).
After preparation, the solution for subcutaneous injection can be used immediately or can be stored at 2°C to 8 °C for up to 24 hours. Do not freeze. After storage at 2°C to 8°C, the solution should be allowed to come to room temperature for approximately 20 minutes before administration. The solution should be administered within 1 hour after removal from the 2°C to 8°C storage.
Instructions for administration of Scapho solution: Tilt the vial to an angle of approximately 45 degrees and position the needle tip at the very bottom of the solution in the vial when drawing the solution into the syringe. DO NOT invert the vial.
Carefully withdraw slightly more than 1.0 mL of the solution for subcutaneous injection from the vial into a 1 mL graduated disposable syringe using a suitable needle (e.g. 21G x 2"). This needle will only be used for withdrawing Scapho into the disposable syringe. Prepare the required number of syringes (1 syringe for the 150 mg dose, 2 syringes for the 300 mg dose).
With the needle pointing upward, gently tap the syringe to move any air bubbles to the top.
Replace the attached needle with a 27G x ½" needle.
Expel the air bubbles and advance the plunger to the 1.0 mL mark.
Clean the injection site with an alcohol swab.
Inject the Scapho solution subcutaneously into the front of thighs, lower abdomen (but not the area 2 inches around the navel (belly button) or outer upper arms. Choose a different site each time an injection is administered. Do not inject into areas where the skin is tender, bruised, red, scaly or hard. Avoid areas with scars or stretch marks.
Any remaining solution in the vial must not be used and should be discarded in accordance with local requirements. Vials are for single use only. Dispose of the used syringe in a sharps container (closable, puncture resistant container). For the safety and health of the patient and others, needles and used syringes must never be re-used.
Incompatibilities: Powder for solution for injection: Scapho should not be mixed with any medication or diluents other than sterile water for injection.
Storage
Store in a refrigerator at 2°C to 8°C.
Store in the original carton to protect from light.
ATC Classification
L04AC10 - secukinumab ; Belongs to the class of interleukin inhibitors. Used as immunosuppressants.
Presentation/Packing
Powd for soln for inj (vial) 150 mg (white, solid, lyophilisate) x 1's.
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