Secukinumab Suppresses Signs and Symptoms of Active Ankylosing Spondylitis

Newswise — BOSTON – Secukinumab, an anti-IL-17A monoclonal antibody biologic drug, showed promise as a treatment for patients with active ankylosing spondylitis, according to new research findings presented this week at the American College of Rheumatology Annual Meeting in Boston.

Ankylosing spondylitis, or AS, is the most common disease in a family of conditions known as spondyloarthritis. Spondyloarthritis is an inflammatory disorder affecting both the axial and peripheral skeleton. It involves bone and the synovium, and often occurs in the entheses, or sites where ligaments and tendons attach to bones. Symptoms of these diseases include inflammation and new bone formation that causes deformities. AS mainly affects the spine, tends to develop in young adults, and affects men more often than women. Frequency of AS in the United States is estimated at 0.5 percent.

A past Phase II study showed that secukinumab suppressed signs and symptoms of active AS after six weeks of treatment. New data from a Phase III study shows the drug’s efficacy after 16 and 52 weeks of treatment, as well as achieving safety standards. Researchers based in the Netherlands, along with colleagues in England, France, Germany, the United States and Switzerland, conducted the research.

“The objective of the study was to evaluate the safety and efficacy of secukinumab versus placebo in patients with active AS, with a primary endpoint at 16 weeks. Additionally, this ongoing study will evaluate the long term safety and efficacy of secukinumab in AS, with the 52 week data presented,” said Dominique Baeten, MD, PhD, professor of clinical immunology and rheumatology at the Academic Medical Center/University of Amsterdam in The Netherlands.

The researchers selected 371 randomized AS patients for the study. The mean age of the participants was 40.1-43.1 years. The mean disease duration of the patients was 6.5 to8.3 years, and their mean BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) score was 6.05-6.51. A little more than a quarter of the patients had had an inadequate response to existing anti-TNF agents to treat the signs and symptoms of their disease.

Patients were randomized to receive either IV secukinumab in 10 mg/kg doses at weeks 0, 2 and 4 followed by subcutaneous secukinumab at 75 mg or 150 mg doses every four weeks thereafter, or placebo according to the same IV and subcutaneous schedule. At week 16 of treatment, both active treatment groups had met the study’s efficacy goals over the placebo group – 59.7 percent of the first group and 60.8 percent of the second group met ASAS20 response levels compared to only 28.7 percent of the placebo group. Significant improvements in secondary measurements of AS signs and symptoms were also seen in patients taking both doses of secukinumab versus placebo at week 16 of treatment. The onset of action of secukinumab was rapid, with significant improvements in primary and secondary outcome parameters seen as early as one week of treatment, and those responses were sustained through week 52.

A significant improvement in signs and symptoms of AS was observed in both TNF blocker naïve patients and TNF blocker incomplete responders. Secukinumab was generally well tolerated by the patients with a safety profile consistent with that observed in the psoriasis and psoriatic arthritis clinical trial programs. The researchers concluded that secukinumab offers rapid, significant and sustained improvement of AS symptoms to patients regardless of their prior exposure to other TNF drugs. They further concluded that secukinumab is safe to use and well tolerated by AS patients.

“Secukinumab is the first drug achieving statistically and clinically significant therapeutic effects in phase III in AS since the introduction of TNF blockers,” said Dr. Baeten. “The efficacy, safety and tolerability profile of secukinumab in AS was confirmed in an independent phase III placebo-controlled trial with subcutaneous dosing of secukinumab. Taken together, these data indicate that secukinumab may become a very useful alternative for TNF blockade in patients with active AS.”

Funding sources for this study included Novartis.

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The American College of Rheumatology is an international professional medical society that represents more than 9,500 rheumatologists and rheumatology health professionals around the world. Its mission is to Advance Rheumatology! The ACR/ARHP Annual Meeting is the premier meeting in rheumatology. For more information about the meeting, visit http://www.acrannualmeeting.org/ or join the conversation on Twitter by using the official #ACR14 hashtag.  Paper Number: 819

Secukinumab, a Monoclonal Antibody to Interleukin-17A, Significantly Improves Signs and Symptoms of Active Ankylosing Spondylitis: Results of a 52-Week Phase 3 Randomized Placebo-Controlled Trial with Intravenous Loading and Subcutaneous Maintenance Dosing

Dominique L. Baeten1, Juergen Braun2, Xenofon Baraliakos2, Joachim Sieper3, Maxime Dougados4, Paul Emery5, Atul A. Deodhar6, Brian Porter7, Ruvie Martin7, Shephard Mpofu8 and Hanno Richards8, 1Department of Clinical Immunology and Rheumatology and Department of Experimental Immunology, Academic Medical Centre/University of Amsterdam, Amsterdam, Netherlands, 2Rheumazentrum Ruhrgebiet, Herne, Germany, 3Charité University Medicine Berlin, Berlin, Germany, 4Université Paris René Descartes and Hôpital Cochin, Paris, France, 5University of Leeds, Leeds, United Kingdom, 6Oregon Health and Sciences University, Portland, OR, 7Novartis Pharma AG, East Hanover, NJ, 8Novartis Pharma AG, Basel, Switzerland

Background/Purpose: A phase 2, proof-of-concept study indicated that secukinumab, an anti–IL-17A monoclonal antibody, suppressed signs and symptoms of active ankylosing spondylitis (AS) by Week (Wk) 6. We present Wk 16 and Wk 52 efficacy and safety data from MEASURE 1 (NCT01358175), a phase 3 study assessing secukinumab vs. placebo (PBO) in patients (pts) with AS.

Methods: Pts with active AS fulfilling modified New York Criteria and BASDAI ≥ 4, despite current or previous therapy with NSAIDs, DMARDs and/or anti-TNF agents, were randomized to receive: i.v. secukinumab 10 mg/kg (Wk 0, 2, 4) followed by s.c. secukinumab 75 mg every 4 wks (10 IV → 75 SC), s.c. secukinumab 150 mg every 4 wks (10 IV → 150 SC), or PBO on same i.v. and s.c. schedules. Endpoints included ASAS20 at Wk 16 (primary), ASAS40, hsCRP, ASAS 5/6, BASDAI, SF-36 PCS, ASQoL and ASAS partial remission. Statistical analyses followed a pre-defined hierarchical hypothesis testing strategy to adjust for multiplicity. PBO pts were re-randomized to secukinumab 75 mg or 150 mg s.c. based on ASAS20 response at Wk 16, with non-responders switched at Wk 16 and responders at Wk 24.

Results: Baseline characteristics of the 371 randomized pts were similar between study arms: mean age 40.1-43.1 years, mean disease duration 6.5-8.3 years, mean BASDAI 6.05-6.51, ~27% inadequate response to anti-TNF agents (TNF-IR). The study met its primary efficacy endpoint with a significantly higher ASAS20 response at Wk 16 in the 10 IV → 75 SC (59.7%) and 10 IV → 150 SC (60.8%) groups vs. PBO (28.7%; P < 0.01 for each dose); ASAS20 response rates in TNF-naïve pts were 60.0%, 66.3% and 32.6%, and in the TNF-IR pts were 58.8%, 45.5% and 18.2%, in the 10 IV → 75 SC, 10 IV → 150 SC and PBO groups, respectively (P< 0.01 vs. PBO). Significant improvements with both doses of secukinumab vs. PBO were observed for all pre-specified secondary endpoints at Wk 16 (Table), with responses sustained through Wk 52. Onset of action of secukinumab was rapid, with significant improvements in ASAS20, ASAS40, hsCRP, ASAS5/6 and BASDAI seen at Wk 1. Through to Wk 16, drug exposure levels were similar in the secukinumab groups due to the i.v. loading doses. Secukinumab was generally well tolerated. At Wk 16, 66.9% of pts in the 10 IV → 75 SC group and 69.6% in the 10 IV → 150 SC group experienced an AE, vs. 55.7% on PBO; SAE rates were 1.6%, 2.4% and 4.1%, respectively. Through Wk 52 visit of the last pt (average exposure [range]: 451.7 [8–757] days), AE/SAE rates were 76.5%/10.1% and 85.1%/9.4% for pts receiving secukinumab 75 or 150 mg s.c., respectively, at any point in the study.

Conclusion: The selective IL-17A inhibitor secukinumab provided rapid and significant improvement of signs and symptoms in pts with active AS, regardless of prior anti-TNF exposure. Improvements were observed from Wk 1 and sustained through 52 wks. Secukinumab was well tolerated through 52 wks with no unexpected safety findings.

Disclosures: D. L. Baeten, Research grants from Boehringer Ingelheim, Jannsen, MSD, Novartis, Pfizer, 2, 9, Consulting fees from AbbVie, Boehringer Ingelheim, BMS, Eli Lilly, Jannsen, MSD, Novartis, Pfizer, Roche, UCB, 5 J. Braun, Honoraria for talks: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis and UCB, 9, Honoraria advisory boards: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis and UCB, 9, Honoraria for paid consultancies: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis and UCB, 5, Grants for studies from Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis and UCB, 2 X. Baraliakos, Research funds from AbbVie, Merck, Pfizer, UCB, Novartis, and Chugai, 2, Consulting fees from AbbVie, Merck, Pfizer, UCB, Novartis, and Chugai, 5, Speaker’s fees from AbbVie, Merck, Pfizer, UCB, Novartis, and Chugai, 8 J. Sieper, Consulting fees from AbbVie, Pfizer, Merck, UCB and Novartis, 5, Research grants from AbbVie, Pfizer and Merck, 2, Speaker's bureau for AbbVie, Pfizer, Merck and UCB, 8 M. Dougados, Research grants from AbbVie, BMS, Eli Lilly, Merck, Pfizer, 2, Consulting fees from Eli Lily, 5 P. Emery, Consulting fees from AbbVie, BMS, Merck, Novartis, Pfizer, Roche, UCB, 5 A. A. Deodhar, Research grants from AbbVie, Amgen, Novartis, Pfizer and UCB, 2, Consulting fees from AbbVie, Celgene, Novartis, Pfizer and UCB, 5 B. Porter, Employee of Novartis , 3, Novartis stock , 1 R. Martin, Employee of Novartis , 3 S. Mpofu, Employee of Novartis , 1, Novartis stock, 3 H. Richards, Employee of Novartis , 3