Secukinumab in Psoriatic Arthritis (PsA)
George Vratsanos, MD, Executive Global Program Head, Immunology & Dermatology, Novartis, discusses new Ph. III data for secukinumab in psoriatic arthritis
Living with PsA: A Patient Perspective
Stephen, from the US, is living with psoriatic arthritis.
Psoriatic Arthritis Patient
Psoriatic arthritis on a patient’s foot with visible red lesions
Hand of Patient with Psoriatic Arthritis
Psoriatic arthritis of the hands, showing shortening and deformation of the hands and fingers
Spondyloarthritis (SpA) Infographic
See below for PDF version
IL-17A in SpA Infographic
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Novartis reports landmark Phase III results for AIN457 (secukinumab) showing rapid and significant efficacy in psoriatic arthritis patients
· Secukinumab demonstrated significant and sustained efficacy versus placebo in improving signs and symptoms of active psoriatic arthritis (PsA) in two pivotal studies1-4
· FUTURE 1 and FUTURE 2 are the first Phase III studies of a selective IL-17A inhibitor in PsA, a painful, debilitating condition causing inflammation of joints and skin5,6
· In FUTURE 1 more than 80% of secukinumab-treated patients experienced no progression of joint structural damage, which affects two-thirds of PsA patients1,2,7,8
· In both studies, secukinumab demonstrated rapid, significant and sustained improvements in skin psoriasis consistent with Phase III psoriasis study results1-4,9
Basel, November 16, 2014 – Novartis announced today first ever results from the pivotal Phase III FUTURE 1 and FUTURE 2 studies showing AIN457 (secukinumab) demonstrated rapid and significant clinical improvements versus placebo in improving the signs and symptoms of psoriatic arthritis (PsA). PsA is part of a family of long-term diseases impacting joints, known as spondyloarthritis (SpA), which also includes ankylosing spondylitis10. There is a high unmet treatment need for patients with PsA. Many patients do not respond to, or tolerate, anti-TNF (tumor-necrosis-factor) medicines, the current standard of care and approximately 45% of people are dissatisfied with current treatments5,11-13. Secukinumab stops the action of interleukin-17A (IL-17A), which is central to the development of inflammatory diseases14,15. These results are being presented today at the American College of Rheumatology (ACR) Congress in Boston, USA.
“We are thrilled to present these landmark Phase III results of secukinmab in PsA, a painful and debilitating condition, with a significant unmet treatment need for patients,” said Vasant Narasimhan, Global Head of Development, Novartis Pharmaceuticals. “We are committed to addressing unmet medical needs in rheumatology by bringing highly effective and long-lasting therapies to patients and these important data are expected to form the basis of our regulatory filing submission in PsA planned in 2015.”
About the data at ACR
Clinically and statistically significant improvements in signs and symptoms of PsA were achieved versus placebo, as measured by a 20% reduction in the American College of Rheumatology response criteria (ACR 20), a standard tool used to assess improvement at Week 2416. Between 50% to 54% of secukinumab patients achieved at least ACR 20 in both FUTURE 1 (150 mg; p<0.0001) and FUTURE 2 (150 and 300 mg; p<0.0001)1-4. This is in comparison to 17.3% and 15.3% of placebo patients who achieved ACR 20 in FUTURE 1 and FUTURE 2, respectively1-4.
Secukinumab patients in all dose groups experienced rapid onset of effect as early as Week 1 in FUTURE 1 (p<0.0001) and Week 3 in FUTURE 2 (150 mg p<0.0001 and 300 mg p<0.001)1-4. Long-term data from FUTURE 1 also confirmed these improvements were sustained through 52 weeks of treatment1,2. Importantly, clinical benefits with secukinumab were observed in patients who had not been previously treated with anti-TNF therapies (anti-TNF naïve), the current standard of care for PsA, and also in patients who had an inadequate or no response to anti-TNFs1,2,12,13. Those who had prior exposure to anti-TNFs included 29.5% and 35% of study participants in FUTURE 1 and FUTURE 2, respectively1-4.
In FUTURE 1, more than 80% of patients experienced no progression of joint structural damage, which is suffered by approximately two-thirds of patients with PsA, and is associated with loss of function and disability1,2,5,6. Improvements in joint damage were shown in both anti-TNF naïve patients and in the patients with inadequate or no response to anti-TNFs1,2. Additionally, secukinumab demonstrated rapid, significant and sustained improvements in skin psoriasis in both FUTURE 1 and FUTURE 2 which was consistent to results of the Phase III psoriasis studies1-4,9.
Secukinumab was well tolerated in both studies, with a safety profile that was consistent with that observed in the large psoriasis clinical trial program involving nearly 4,000 patients1-4,17. The most common adverse events (AEs) were the common cold, headache and upper respiratory tract infection1-4,17.
About Secukinumab Psoriatic Arthritis Phase III trials
FUTURE 1 and FUTURE 2 are the first multi-center, randomized, placebo-controlled Phase III studies to evaluate the efficacy of secukinumab in IL-17A inhibition in PsA. In the FUTURE 1 study patients received an intravenous loading dose every two weeks for the first four weeks of treatment followed by monthly subcutaneous doses of 75 mg or 150 mg compared to placebo, and FUTURE 2 compared subcutaneous loading dose secukinumab 75 mg, 150 mg and 300 mg to placebo1-4. The intravenous loading period used in FUTURE 1 was designed to provide high systemic exposure for induction of response, in keeping with the initial proof of concept study in PsA with secukinumab1,2. FUTURE 2 utilized an administration route (subcutaneous loading dose) and dose range (up to 300 mg) that is more consistent with the psoriasis program3,4. A combined total of more than 1,000 patients were enrolled in the studies1-4.
Both studies met their primary endpoint, the American College of Rheumatology response criteria (ACR 20) at Week 24 – a standard tool used to assess improvement (at least 20% improvement) in PsA signs and symptoms – and findings were consistent across the two studies1-4,16:
· FUTURE 1, 50.5% and 50.0% for both secukinumab treatment arms, respectively, versus 17.3% for placebo; p<0.0001
· FUTURE 2, 29.3% for secukinumab 75 mg (p<0.05); 51.0% and 54.0% for secukinumab 150 mg and 300 mg, respectively, versus 15.3% for placebo; p<0.0001
Full results of secondary endpoints will be presented at ACR. Secondary endpoints at Week 24 in FUTURE 1 and FUTURE 2 included1-4:
· 75% and 90% improvement in Psoriasis Area-and-Severity Index score (PASI 75 and PASI 90)
· Change from baseline in 28-joint Disease Activity Score using C-reactive protein (DAS28 – CRP)
· Physical function assessed using the Medical Outcome Short Form (36) Health Survey physical component summary scores (SF-36 PCS)
· Physical function assessed using the Health Assessment Questionnaire Disability Index (HAQ-DI)
· ACR 50 (American College of Rheumatology response criteria) response
· Proportion of subjects with dactylitis and enthesitis
· Overall safety and tolerability of each secukinumab regimen compared with placebo
Additional secondary endpoint at Week 24 in FUTURE 11-2:
· Radiographic progression assessed using the van der Heijde modified total Sharp score (mTSS)
About psoriatic arthritis (PsA)
Closely associated with psoriasis, psoriatic arthritis (PsA) is part of a family of long-term diseases impacting joints, known as spondyloarthritis (SpA); approximately 30% of patients with psoriasis have psoriatic arthritis10,11. Psoriatic arthritis (PsA) is a debilitating, long-lasting inflammatory disease linked with significant disability, poor quality of life and reduced life expectancy11. PsA is associated with joint pain and stiffness, skin and nail psoriasis, swollen toes and fingers, persistent painful tendonitis, and irreversible joint damage6. Between 0.3% and 1% of the general population may be affected by PsA and as many as one in four people with psoriasis may have undiagnosed PsA11,15.
About secukinumab (AIN457) and interleukin-17A (IL-17A)
Secukinumab (AIN457) is a human monoclonal antibody that selectively neutralizes IL-17A14. Secukinumab is the first IL-17A inhibitor with positive Phase III results for the treatment of PsA and AS. Research shows that IL-17A plays an important role in driving the body’s immune response in psoriasis and other inflammatory arthritic diseases, including PsA and AS15.
In addition to PsA, secukinumab is also in clinical trials for the treatment of ankylosing spondylitis (AS) and rheumatoid arthritis (RA). Global regulatory applications for secukinumab in AS and PsA are planned for 2015. This follows the secukinumab global regulatory applications for moderate-to-severe plaque psoriasis which were filed in October 2013 with approvals anticipated in late 2014 or early 2015.
Full Press Release
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