Key clinical-trial evidence for secukinumab

Author:Anoma Ranaweera B.V.Sc; PhD (Clinical Biochemistry, University of Liverpool, UK). Chief Editor: Dr Amanda Oakley, Dermatologist, Hamilton, New Zealand, March 2015.

In January 2015, the US Food and Drug Administration (FDA) approved secukinumab (Cosentyx™, Novartis, USA) for the treatment of moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy (a drug that is absorbed into the bloodstream and distributed to all parts of the body) or phototherapy (light therapy).

The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorisation for secukinumab.

Secukinumab is a human IgG1 monoclonal antibody that selectively binds to the cytokine interleukin-17A (IL-17A) inhibiting its pro-inflammatory effects.

IL-17A is a key cytokine (messenger protein) involved in the development of plaque psoriasis, and is found in high concentrations in psoriasis plaques.

The approval of secukinumab is based on the efficacy and safety outcomes from 10 Phase II and III studies which included over 3,990 patients with moderate-to-severe plaque psoriasis. These trials included four pivotal Phase III trials, ERASURE, FIXTURE, FEATURE and JUNCTURE studies detailed below.

ERASURE study – efficacy

Table 1
END POINT SECUKINUMAB 300MG SECUKINUMAB 150MG PLACEBO
Co-primary efficacy endpoint at week 12 – no./total no. patients (%)
PASI 75 200/245 (81.6) 174/243 (71.6) 11/246 (4.5)
Response of 0 or 1 on the modified investigator’s global assessment 160/245 (65.3) 125/244 ( (51.2) 6/246 (2.4)
Key secondary efficacy endpoints – no./total no. patients (%)
PASI 90 at week 12 145/245 (59.2) 95/243 (59.2) 3/246 (1.2)
Maintenance of PASI 75 from week 12 to week 52 161/200 (80.5) 126/174 (72.4) Not evaluated
Maintenance of 0 or 1 response on modified investigator’s global assessment from wk 12 to wk 52 119/160 (74.4) 74/125 (59.2) Not evaluated
Other efficacy endpoints – no./total no. patients (%)
PASI 100 at week 12 70/245 (28.6) 31/243 (12.8) 2/246 (0.8)
Dermatology Life Quality Index* – mean score
Baseline 13.9 13.4 12.0
Week 12 2.5 3.3 10.9
Absolute change -11.4 -10.1 -1.1
*scores on the dermatology life quality index vary from 0–30 with higher scores indicating a greater effect of disease on quality of life.

Safety – ERASURE study

Table2
Adverse event Secukinumab 300mg (n= 245)
No. pts (%)
Secukinumab 100mg (n = 245)
No. pts (%)
Placebo (n = 247)
No. pts (%)
Nasopharyngitis 22 (9.0) 23 (9.4) 19 (7.7)
Headache 12 (4.9) 13 (5.3) 7 (2.8)
Upper respiratory tract infections 9 (3.7) 10 (4.1) 0
Pruritus (itch) 9 (3.7) 8 (3.3) 5 (2.0)
Oropharyngeal pain 4 (1.6) 10 (4.1) 3 (1.2)
Fatigue 2 (0.8) 8 (3.3) 2 (0.8)
Hypertension 0 9 (3.7) 3 (1.2)
Influenza-like illness 5 (2.0) 3 (1.2) 3 (1.2)

FIXTURE study – efficacy

Table 3
End point Secukinumab 300mg Secukinumab 150mg Etanercept 50mg Placebo
Co-primary efficacy endpoint at week 12 – no./total no. patients (%)
PASI 75 249/323 (77.1) [P<0.001 vs etanercept and placebo] 219/327 (67.0) [P<0.001 vs etanercept and placebo] 142/323 (44.0) 16/324 (4.9)
Response of 0 or 1 on the modified investigator’s global assessment 202/323 (62.5) [P<0.001 vs etanercept and placebo] 167/327 (51.1) [P<0.001 vs etanercept and placebo] 67/323 (20.7) 5/324 (1.5)
Key secondary efficacy endpoints – no./total no. patients (%)
PASI 90 at week 12 175/323 (54.2) [P<0.001 vs etanercept] 137/327 (41.9) [P<0.001 vs etanercept] 67/323 (20.7) Not evaluated
Maintenance of PASI 75 from week 12 to week 52 210/249 (84.3) [P<0.001 vs etanercept] 180/219 (82.2)
[P = 0.009 vs etanercept] 103/142 (72.5) Not evaluated
Maintenance of 0 or 1 response on modified investigator’s global assessment from wk 12 to wk 52 161/202 (79.7) [P<0.001 vs etanercept] 113/167 (67.7) [P=0.002 vs etanercept] 50/88 (56.8] Not evaluated
Other efficacy endpoints – no./total no. patients (%)
PASI 100 at week 12 78/232 (24.1) [P <0.001 vs etanercept] 47/327 (14.4) [P <0.001 vs etanercept] 14/323 (4.3) 0/324
Dermatology Life Quality Index* – mean score
Baseline 13.3 13.4 13.4 13.4
Week 12 2.9 3.7 5.5 11.5
Absolute change -10.4 -9.7 -7.9 -1.9
*scores on the dermatology life quality index vary from 0–30 with higher scores indicating a greater effect of disease on quality of life.

Safety – FIXTURE study

The most common adverse reactions (occurring in > 2% of patients) at week 12 are summarised in table 4.

Table 4
Adverse Event
>No. pts (%)
Secukinumab 300mg
(n = 326)
Secukinumab 150mg
(n = 327)
Etanercept
(n = 323)
Placebo
(n = 327)
Nasopharyngitis 35 (10.7) 45 (13.8) 36 (11.1) 26 (8.0)
Headache 30 (9.2) 16 (4.9) 23 (7.1) 23 (7.0)
Diarrhoea 17(5.2) 12 (3.7) 11 (3.4) 6 (1.8)
Pruritus (itch) 8 (2.5) 12 (3.7) 8 (2.5) 11 (3.4)
Arthralgia (joint pain) 5 (1.5) 14 (4.3) 12 (3.7) 10 (3.1)
Upper respiratory infections 7 (2.1) 10 (3.1) 7 (2.2) 3 (0.9)
Back pain 8 (2.5) 8 (2.4) 9 (2.8) 6 (1.8)
Cough 11 (3.4) 5 (1.5) 4 (1.2) 4 (1.2)
Hypertension (high blood pressure) 5 (1.5) 10 (3.1) 5 (1.5) 4 (1.2)
Nausea 8 (2.5) 6 (1.8) 4 (1.2) 7 (2.1)
Oropharyngeal pain (pain in mouth/throat) 9 (2.8) 5 (1.5) 4 (1.2) 7 (2.1)
Infection or infestation 87 (26.7%) 101 (30.9) 79 (24.5) 63 (19.3)

FEATURE study

Table 5
End point Secukinumab 300mg (n = 59) Secukinumab 150mg (n = 59) Placebo (n = 59)
PASI 75 response (n %) 44 (75) 41 (69) 0
IGA of clear or almost clear (n %) 40 (68) 31 (53) 0

Adverse reactions that occurred at a higher incidence (>2%) in secukinumab-treated patients vs placebo through to week 12 included nasopharyngitis, diarrhoea and upper respiratory tract infections.

JUNCTURE study

Table 6
End point Secukinumab 300mg (n = 60) Secukinumab 150mg (n = 61) Placebo (n = 61)
PASI 75 response (n %) 52 (87) 43 (70) 2 (3)
IGA of clear or almost clear (n %) 44 (43) 32 (52) 0 (0)

Adverse reactions that occurred at a higher incidence (>2%) in secukinumab-treated patients vs placebo through to week 12 included nasopharyngitis, diarrhoea and upper respiratory tract infections.

Future directions for secukinumab

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