Cosentyx for the treatment of active non-radiographic axial spondyloarthritis, approved by FDA
The FDA ( US Food and Drug Administration ) has approved Cosentyx ( Secukinumab ) for the treatment of active non-radiographic axial spondyloarthritis ( nr-axSpA ), confirming Cosentyx efficacy in addressing the axial spondyloarthritis ( axSpA ) disease spectrum.
The approval of Cosentyx for nr-axSpA is based on efficacy and safety outcomes from the PREVENT phase III study, which included 555 adults with active nr-axSpA that were biologic treatment naïve or had an inadequate response / were intolerant to an anti-tumor necrosis factor-α therapy ( anti-TNFs ).
Cosentyx met the primary endpoints achieving statistically significant improvements versus placebo in the signs and symptoms of nr-axSpA, as measured by at least a 40% improvement in the Assessment of Spondyloarthritis International Society ( ASAS40 ) response criteria in biologic-naïve individuals at week 52.
nr-axSpA patients treated with Cosentyx showed improvement in both load and without load arms compared to placebo-treated patients at week 16 in health-related quality of life as measured by the Ankylosing Spondylitis Quality of Life ( ASQoL ) questionnaire ( least squares mean change: week 16: -3.5 and -3.6 -vs -1.8, respectively ).
General health status and quality of life was assessed by the Short Form health survey ( SF-36 ).
At week 16, patients treated with Cosentyx showed greater improvement from baseline in the SF-36 physical component summary ( PCS ) score and in the mental component summary ( MCS ) score10.
The safety profile of Cosentyx in the PREVENT trial was shown to be consistent with previous clinical trials. No new safety signals were detected.
nr-axSpA is part of the axSpA spectrum, which is characterized by inflammatory arthritis of the spine associated with chronic inflammatory back pain.
The axSpA disease spectrum also includes ankylosing spondylitis ( AS ), in which joint damage is visible on x-ray, and nr-axSpA, in which joint damage is generally not visible on x-ray.
The physical limitations of axSpA can affect activities of daily living as well as leisure activities causing limitations for patients.
Cosentyx is the first and only fully-human biologic that directly inhibits interleukin-17A ( IL-17A ), an important cytokine involved in the inflammation and development of psoriatic arthritis ( PsA ), moderate to severe plaque psoriasis ( PsO ), ankylosing spondylitis ( AS ) and nr-axSpA. Cosentyx has been studied clinically for more than 13 years.
PREVENT is a two-year randomized, double-blind, placebo-controlled phase III study ( with a two-year extension phase) to investigate the efficacy and safety of Cosentyx, in patients with active nr-axSpA.
The study enrolled 555 male and female adult patients with active nr-axSpA ( with onset before 45 years of age, spinal pain rated as greater than or equal to 40/100 on a visual analog scale ( VAS ) and Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) 4 or more ) and who had been taking at least two different non-steroidal anti-inflammatory drugs ( NSAIDs ) at the highest dose up to 4 weeks prior to study start.
Patients may have previously taken a TNF inhibitor ( not more than one ) but had had an inadequate response. Of the 555 patients enrolled in the study, 501 ( 90% ) were biologic naive.
Patients were allocated to one of three treatment groups: Cosentyx 150 mg subcutaneously with loading dose ( induction: 150 mg Secukinumab subcutaneously weekly for 4 weeks, then maintenance with 150 mg Secukinumab monthly ); Cosentyx 150 mg no loading dose ( 150 mg Secukinumab subcutaneously monthly ), or placebo ( induction of subcutaneously weekly for 4 weeks, followed by maintenance of once-monthly ).
The primary endpoints are the proportion of biologic-naïve patients achieving an ASAS40 response with Cosentyx 150 mg at weeks 16 and 52. Secondary endpoints include change in BASDAI over time and change in the Ankylosing Spondylitis Disease Activity Score with CRP ( ASDAS-CRP ).
ASAS40 is achieved when there is a measure of an improvement of at least 40% and an improvement of at least 20 units on a 0–100 scale in at least three of the following domains: Patient global assessment, Pain assessment, Function ( Bath Ankylosing Spondylitis Functional Index [ BASFI ] ), and Inflammation ( morning stiffness severity and duration ) and no worsening in the remaining domains.
BASDAI assesses a patient’s disease activity on six measures: fatigue, spinal pain, joint pain / swelling, enthesitis, morning stiffness duration and morning stiffness severity. ( Xagena )
Source: Novartis, 2020