Updated safety of cladribine tablets in the treatment of patients with multiple sclerosis: Integrated safety analysis and post-approval data
ECTRIMS Online Library. Cook S. 09/13/19; 278591; P1390
S Cook
S Cook
Contributions
Abstract

Abstract: P1390

Type: Poster Sessions

Abstract Category: Therapy - Long-term treatment monitoring

S. Cook1, G. Giovannoni2, T. Leist3, G. Comi4, S. Syed5, A. Nolting6, D. Damian5, R. Schick6

1Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, NJ, United States, 2Queen Mary University of London, Blizard Institute, Barts and The London School of Medicine and Dentistry, London, United Kingdom, 3Division of Clinical Neuroimmunology, Jefferson University, Comprehensive MS Center, Philadelphia, PA, United States, 4Department of Neurology and Institute of Experimental Neurology, Università Vita-Salute San Raffaele, Ospedale San Raffaele, Milan, Italy, 5EMD Serono Research & Development Institute Inc., Billerica, MA, United States, 6Merck Healthcare KGaA, Darmstadt, Germany

Introduction: Pooling of long-term safety data for integrated analysis from the clinical trial program allows comprehensive characterization of the Cladribine Tablets (CT) 10 mg (3.5 mg/kg cumulative dose over 2 years; referred to as CT3.5) safety profile in patients with relapsing multiple sclerosis (RMS).
Objectives: To use the latest integrated safety data for CT, from clinical studies including final data from the PREMIERE registry, to provide an update to the previously reported treatment emergent adverse event (TEAE) profile. Additionally, to report post-approval safety data from Europe.
Methods: The monotherapy oral cohort (CT3.5, N=923, patient-years [PY]=3936.69; placebo [PBO], N=641, PY=2421.47) was derived from the CLARITY, CLARITY Extension, and ORACLE-MS trials, and the PREMIERE registry. Incidences per 100PY were calculated for adverse events, cumulative to the end of PREMIERE. Adverse drug reactions (ADRs) including serious ADRs (SADRs; implied causality) from post-approval sources are also summarised.
Results: Demographics reported at first dosing date were found to be balanced among treatment groups, including mean age (37.8 years, CT3.5; 37.2 years, PBO), proportion of females (66.3%, CT3.5; 66.1%, PBO) and proportion of patients with prior disease modifying drug experience (19.9%, CT3.5; 20.4%, PBO). Incidences per 100PY for experiencing ≥1 serious TEAE were 3.80 (CT3.5) and 3.05 (PBO). Incidences per 100PY for serious lymphopenia (preferred term [PT]) was 0.10 for CT3.5 and 0 for PBO. For serious infections and infestations (system organ class), incidences per 100PY were 0.60 (CT3.5) and 0.42 (PBO); for serious herpes zoster (PT): 0.05 (CT3.5) and 0 (PBO). Incidences per 100PY for malignant tumours were 0.26 (CT 3.5) and 0.12 (PBO). Separately, 922 ADRs from post-approval sources were reported in the Periodic Benefit-Risk Evaluation Report, of which 136 were SADRs; none of which are new safety findings for CT3.5.
Conclusions: This integrated analysis of trial data, exclusively focused on the frequency of serious TEAEs with CT3.5 in RMS patients, further establishes the safety profile of this dose. This profile is consistent with the previously published integrated safety analysis profile. No new major safety findings were identified in this latest dataset which includes final data from the PREMIERE registry. The pattern of post-approval ADRs was consistent with the clinical safety profile for CT3.5.
Disclosure:
CLARITY: NCT00213135
CLARITY Extension: NCT00641537
ORACLE-MS: NCT00725985
PREMIERE: NCT01013350
Funding disclosure: This study was sponsored by EMD Serono Inc, a business of Merck KGaA, Darmstadt, Germany.
Author disclosure:
SC: received honoraria for lectures/consultations from Merck Healthcare KGaA, Bayer HealthCare, Sanofi-Aventis, Neurology Reviews, Biogen Idec, Teva Pharmaceuticals, and Actinobac Biomed Inc.; has served on advisory boards for Bayer HealthCare, Merck Healthcare KGaA, Actinobac Biomed, Teva Pharmaceuticals, and Biogen Idec; and received grant support from Bayer HealthCare.
GG: received speaker honoraria and consulting fees from Abbvie, Actelion, Atara Bio, Almirall, Bayer Schering Pharma, Biogen Idec, FivePrime, GlaxoSmithKline, GW Pharma, Merck & Co., Merck Healthcare KGaA, Pfizer Inc, Protein Discovery Laboratories, Teva Pharmaceutical Industries Ltd, Sanofi-Genzyme, UCB, Vertex Pharmaceuticals, Ironwood, and Novartis; and has received research support unrelated to this study from Biogen Idec, Merck & Co., Novartis, and Ironwood.
TL: received consultancy fees or clinical research grants from Acorda, Bayer, Biogen, Daiichi, EMD Serono, Novartis, ONO, Pfizer, Teva Neuroscience.
GC: received consulting fees from Novartis, Teva Pharmaceutical Industries Ltd., Sanofi-Aventis, Merck, Receptos, Biogen Idec, Genentech-Roche, and Bayer Schering; lecture fees from Novartis, Teva Pharmaceutical Ind. Ltd., Sanofi-Aventis, Merck, Biogen Dompè, Bayer Schering, and Serono Symposia International Foundation; and trial grant support from Novartis, Teva Pharmaceutical Ind. Ltd., Sanofi-Aventis, Receptos, Biogen Idec, Genentech-Roche, Merck, Biogen Dompè, and Bayer Schering.
SS and DD: employees of EMD Serono Research & Development Institute Inc., a business of Merck KGaA, Darmstadt, Germany.
AN and RS: employees of Merck Healthcare KGaA, Darmstadt, Germany.

Abstract: P1390

Type: Poster Sessions

Abstract Category: Therapy - Long-term treatment monitoring

S. Cook1, G. Giovannoni2, T. Leist3, G. Comi4, S. Syed5, A. Nolting6, D. Damian5, R. Schick6

1Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, NJ, United States, 2Queen Mary University of London, Blizard Institute, Barts and The London School of Medicine and Dentistry, London, United Kingdom, 3Division of Clinical Neuroimmunology, Jefferson University, Comprehensive MS Center, Philadelphia, PA, United States, 4Department of Neurology and Institute of Experimental Neurology, Università Vita-Salute San Raffaele, Ospedale San Raffaele, Milan, Italy, 5EMD Serono Research & Development Institute Inc., Billerica, MA, United States, 6Merck Healthcare KGaA, Darmstadt, Germany

Introduction: Pooling of long-term safety data for integrated analysis from the clinical trial program allows comprehensive characterization of the Cladribine Tablets (CT) 10 mg (3.5 mg/kg cumulative dose over 2 years; referred to as CT3.5) safety profile in patients with relapsing multiple sclerosis (RMS).
Objectives: To use the latest integrated safety data for CT, from clinical studies including final data from the PREMIERE registry, to provide an update to the previously reported treatment emergent adverse event (TEAE) profile. Additionally, to report post-approval safety data from Europe.
Methods: The monotherapy oral cohort (CT3.5, N=923, patient-years [PY]=3936.69; placebo [PBO], N=641, PY=2421.47) was derived from the CLARITY, CLARITY Extension, and ORACLE-MS trials, and the PREMIERE registry. Incidences per 100PY were calculated for adverse events, cumulative to the end of PREMIERE. Adverse drug reactions (ADRs) including serious ADRs (SADRs; implied causality) from post-approval sources are also summarised.
Results: Demographics reported at first dosing date were found to be balanced among treatment groups, including mean age (37.8 years, CT3.5; 37.2 years, PBO), proportion of females (66.3%, CT3.5; 66.1%, PBO) and proportion of patients with prior disease modifying drug experience (19.9%, CT3.5; 20.4%, PBO). Incidences per 100PY for experiencing ≥1 serious TEAE were 3.80 (CT3.5) and 3.05 (PBO). Incidences per 100PY for serious lymphopenia (preferred term [PT]) was 0.10 for CT3.5 and 0 for PBO. For serious infections and infestations (system organ class), incidences per 100PY were 0.60 (CT3.5) and 0.42 (PBO); for serious herpes zoster (PT): 0.05 (CT3.5) and 0 (PBO). Incidences per 100PY for malignant tumours were 0.26 (CT 3.5) and 0.12 (PBO). Separately, 922 ADRs from post-approval sources were reported in the Periodic Benefit-Risk Evaluation Report, of which 136 were SADRs; none of which are new safety findings for CT3.5.
Conclusions: This integrated analysis of trial data, exclusively focused on the frequency of serious TEAEs with CT3.5 in RMS patients, further establishes the safety profile of this dose. This profile is consistent with the previously published integrated safety analysis profile. No new major safety findings were identified in this latest dataset which includes final data from the PREMIERE registry. The pattern of post-approval ADRs was consistent with the clinical safety profile for CT3.5.
Disclosure:
CLARITY: NCT00213135
CLARITY Extension: NCT00641537
ORACLE-MS: NCT00725985
PREMIERE: NCT01013350
Funding disclosure: This study was sponsored by EMD Serono Inc, a business of Merck KGaA, Darmstadt, Germany.
Author disclosure:
SC: received honoraria for lectures/consultations from Merck Healthcare KGaA, Bayer HealthCare, Sanofi-Aventis, Neurology Reviews, Biogen Idec, Teva Pharmaceuticals, and Actinobac Biomed Inc.; has served on advisory boards for Bayer HealthCare, Merck Healthcare KGaA, Actinobac Biomed, Teva Pharmaceuticals, and Biogen Idec; and received grant support from Bayer HealthCare.
GG: received speaker honoraria and consulting fees from Abbvie, Actelion, Atara Bio, Almirall, Bayer Schering Pharma, Biogen Idec, FivePrime, GlaxoSmithKline, GW Pharma, Merck & Co., Merck Healthcare KGaA, Pfizer Inc, Protein Discovery Laboratories, Teva Pharmaceutical Industries Ltd, Sanofi-Genzyme, UCB, Vertex Pharmaceuticals, Ironwood, and Novartis; and has received research support unrelated to this study from Biogen Idec, Merck & Co., Novartis, and Ironwood.
TL: received consultancy fees or clinical research grants from Acorda, Bayer, Biogen, Daiichi, EMD Serono, Novartis, ONO, Pfizer, Teva Neuroscience.
GC: received consulting fees from Novartis, Teva Pharmaceutical Industries Ltd., Sanofi-Aventis, Merck, Receptos, Biogen Idec, Genentech-Roche, and Bayer Schering; lecture fees from Novartis, Teva Pharmaceutical Ind. Ltd., Sanofi-Aventis, Merck, Biogen Dompè, Bayer Schering, and Serono Symposia International Foundation; and trial grant support from Novartis, Teva Pharmaceutical Ind. Ltd., Sanofi-Aventis, Receptos, Biogen Idec, Genentech-Roche, Merck, Biogen Dompè, and Bayer Schering.
SS and DD: employees of EMD Serono Research & Development Institute Inc., a business of Merck KGaA, Darmstadt, Germany.
AN and RS: employees of Merck Healthcare KGaA, Darmstadt, Germany.

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