Talk: Efficacy and Safety of Canakinumab (Ilaris) in A Large Cohort of Patients Across Different Severity Phenotypes of Cryopyrin Associated Periodic Syndrome (CAPS) (2009 ACR/ARHP Annual Scientific Meeting)

Monday, October 19, 2009: 5:15 PM

203 B (Pennsylvania Convention Center)

J.B. Kuemmerle-Deschner¹, H.J. Lachmann², E. Hachulla³, J. Hoyer⁴, J. Smith⁵, K. Leslie⁶, I. Kone-Paut⁷, J. Braun⁸, A. Widmer⁹, N. Patel¹⁰, R. Preiss¹⁰ and P.N. Hawkins², ¹Universitätsklinikum Tübingen, Klinik fuer Kinder-und Jugendmedizin, Germany, ²Royal Free and University College Medical School, London, United Kingdom, ³Hopital Claude Huriez, Lille Cedex, France, ⁴Univ.-Klinikum Gießen und Marburg, Marburg, Germany, ⁵University of Wisconsin Hospital and Clinics, Madison, WI, ⁶UCSF, School of Medicine, San Francisco, CA, ⁷Hopital Kremlin Bicetre, Le Kremlin Bicetre, France, ⁸Rheumazentrum Ruhrgebiet, Herne, Germany, ⁹Novartis, Basel, Switzerland, ¹⁰Novartis, East Hanover, NJ

Presentation Number: 1235

Purpose: CAPS (disease spectrum consisting of FCAS, MWS, NOMID) is a rare hereditary, autosomal dominant, systemic inflammatory disease associated with excessive production of IL-1β. The fully human monoclonal antibody canakinumab provides prolonged selective blockade of IL-1β.

Method: Patients enrolled in this open-label multi-center study were canakinumab naïve or rolled over from earlier Phase II/III studies. Patients received canakinumab 150 mg s.c. or 2 mg/kg s.c. (≤40 kg) every 8 weeks. The primary objective of this ongoing trial is to assess the long-term safety and tolerability of canakinumab in CAPS patients. Secondary objectives included assessment of response (for naïve patients), maintenance of response, percentage of patients requiring dose adjustment, and immunogenicity of canakinumab. A relapse was defined as: serum levels of CRP and/or serum amyloid A protein (SAA) >30 mg/L and physician’s global assessment of disease activity >minimal or physician’s global assessment of disease activity =minimal along with the assessment of skin disease >minimal.

Results: Out of 98 patients (19 FCAS; 69 MWS; 9 MWS/NOMID; 1 cold urticaria/protocol deviation; 19 pediatric) aged 5-69 years enrolled in the study, 44 patients were canakinumab-naïve, while 54 had previously received canakinumab in another study. The median duration of exposure to canakinumab was 113 days (range 9-232 days) and the mean number of injections per patient was 2.9 (range 1-9) at the time of this interim analysis. A complete response by Day 8 was seen in 41/44 (93.2%) canakinumab-naïve patients. 13 patients had missing relapse assessment data at the interim analysis cut off. Of the remaining 85 patients, 77 had no relapse (90.6%), 5 experienced a relapse (5.9%), and 3 naïve patients did not achieve a complete response. At least one dose adjustment was required in 16 patients (16.3%). AEs were predominantly mild to moderate in severity, the most frequent AE was nasopharyngitis. Two patients discontinued due to AEs (1 due to worsening of multiple sclerosis like lesions and another due to MWS flare). Serious AEs were reported in 5 patients and resolved while on treatment. The majority of patients (94.9%) had no injection site reactions, 5.1% reported reactions, which were all mild. No anti-canakinumab antibodies were observed.

Conclusion: For CAPS patients, canakinumab administered every 8 weeks, provided rapid improvement of symptoms and sustained remission in a large cohort of patients across all disease severity phenotypes.

Keywords: Muckle-Wells syndrome, interleukins (IL) and monoclonal antibodies

Disclosure: J. B. Kuemmerle-Deschner, Novartis Pharmaceutical Corporation, 3, Novartis Pharmaceutical Corporation, 5 ; H. J. Lachmann, EU framework 7grant, 2, Novartis Pharmaceutical Corporation, 5 ; E. Hachulla, Novartis Pharmaceutical Corporation, 5 ; J. Hoyer, None; J. Smith, None; K. Leslie, None; I. Kone-Paut, Novartis Pharmaceutical Corporation, 5 ; J. Braun, Novartis Pharmaceutical Corporation, 2, Centocor, Inc., 6, Schering-Plough, 6, Wyeth Pharmaceuticals, 6, Amgen, 6, Abbott Laboratories, 6, BMS, 6, Roche Pharmaceuticals, 6, Chugai, 6, Pfizer Inc, 6, MSD, 6 ; A. Widmer, Novartis Pharmaceutical Corporation, 1, Novartis Pharmaceutical Corporation, 3 ; N. Patel, Novartis Pharmaceutical Corporation, 1, Novartis Pharmaceutical Corporation, 3 ; R. Preiss, Novartis Pharmaceutical Corporation, 1, Novartis Pharmaceutical Corporation, 3 ; P. N. Hawkins, Novartis Pharmaceutical Corporation, 5 .

1235 - Efficacy and Safety of Canakinumab (Ilaris) in A Large Cohort of Patients Across Different Severity Phenotypes of Cryopyrin Associated Periodic Syndrome (CAPS)