Contributions
Abstract: P875
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Introduction: Pooling of long-term safety data for integrated analysis allowed comprehensive characterisation of the Cladribine Tablets (CT) safety profile in patients at the earliest stages, or more advanced stages of relapsing multiple sclerosis (RMS). Previous characterisation of a monotherapy oral cohort treated with CT 3.5 mg/kg (CT3.5) included cumulative safety data up to Feb 2015, >3 years beyond completion of the last clinical study.
Objectives: Two-year update of the serious treatment emergent adverse event (TEAE) profile from the CT3.5 integrated safety analysis.
Methods: The monotherapy oral cohort was derived from the CLARITY, CLARITY Extension, and ORACLE-MS trials, and the PREMIERE registry. It included 923 patients who received CT3.5 and 641 patients who received placebo (PBO). Adjusted adverse events incidences per 100 patient-years (Adj-AE per 100PY) were calculated. Two data cut-offs were compared: cumulative to Feb 2015 (previously presented, defined here as “Period 1” [P1]) and cumulative to May 2017 (updated, defined as “Period 2” [P2]). Serious adverse drug reactions (ADR; implied causality) from post-marketing sources are also summarised.
Results: Demographics at respective study enrolment, including age (36.5 years, CT3.5), proportion of females (66.3%, CT3.5) and prior disease modifying drug experience, were balanced among treatment groups. Adj-AE per 100PY rates for experiencing ≥1 serious TEAE were 3.88 (CT3.5) and 3.24 (PBO) in P2, 4.00 (CT3.5) and 3.57 (PBO) in P1. Adj-AE per 100PY for serious lymphopenia (preferred term [PT]) were 0.11 (CT3.5) and 0 (PBO) in P2, 0.12 (CT3.5) and 0 (PBO) in P1; for serious infection and infestations (system organ class [SOC]): 0.63 (CT3.5) and 0.44 (PBO) in P2, 0.69 (CT3.5) and 0.50 (PBO) in P1; for serious herpes zoster (PT): 0.05 (CT3.5) and 0 (PBO) in P2, 0.06 (CT3.5) and 0 (PBO) in P1. Adj-AE per 100PY for serious neoplasms, benign, malignant and unspecified (SOC) were 0.65 (CT3.5) and 0.35 (PBO) in P2, 0.74 (CT3.5) and 0.50 (PBO) in P1. Regarding post-marketing data, 11 serious ADRs were reported; none are new safety findings for CT3.5.
Conclusions: This integrated analysis confirms the serious TEAE profile associated with CT3.5 treatment of patients with early and active RMS. The updated profile (P2) was generally consistent with that from 2 years prior (P1). No new major safety findings were identified in the updated dataset, where patients were followed for up to 10 years.
Disclosure: The CLARITY study: NCT00213135; The CLARITY Extension study: NCT00641537; The ORACLE-MS study: NCT00725985; The PREMIERE registry: NCT01013350. Disclosures: This study was sponsored by EMD Serono Inc, a business of Merck KGaA, Darmstadt, Germany (in the USA), and Merck Serono SA, Geneva, an affiliate of Merck KGaA Darmstadt, Germany (ROW). Author disclosures
SC has received honoraria for lectures/consultations from Merck, Bayer HealthCare, Sanofi-Aventis, Neurology Reviews, Biogen Idec, Teva Pharmaceuticals, and Actinobac Biomed Inc.; has served on advisory boards for Bayer HealthCare, Merck, Actinobac Biomed, Teva Pharmaceuticals, and Biogen Idec; and received grant support from Bayer HealthCare. GG has received speaker honoraria and consulting fees from Abbvie, Atara Bio, Almirall, Bayer Schering Pharma, Biogen Idec, FivePrime, GlaxoSmithKline, GW Pharma, Merck, , 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, Novartis, and Ironwood. TL has received consultancy fees or clinical research grants from Acorda, Bayer, Biogen, Daiichi, EMD Serono, Novartis, ONO, Pfizer, Teva Neuroscience. SS is an employee of EMD Serono, Inc., a business of Merck KGaA, Darmstadt, Germany. AN and RS are employees of Merck KGaA, Darmstadt, Germany.
Abstract: P875
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Introduction: Pooling of long-term safety data for integrated analysis allowed comprehensive characterisation of the Cladribine Tablets (CT) safety profile in patients at the earliest stages, or more advanced stages of relapsing multiple sclerosis (RMS). Previous characterisation of a monotherapy oral cohort treated with CT 3.5 mg/kg (CT3.5) included cumulative safety data up to Feb 2015, >3 years beyond completion of the last clinical study.
Objectives: Two-year update of the serious treatment emergent adverse event (TEAE) profile from the CT3.5 integrated safety analysis.
Methods: The monotherapy oral cohort was derived from the CLARITY, CLARITY Extension, and ORACLE-MS trials, and the PREMIERE registry. It included 923 patients who received CT3.5 and 641 patients who received placebo (PBO). Adjusted adverse events incidences per 100 patient-years (Adj-AE per 100PY) were calculated. Two data cut-offs were compared: cumulative to Feb 2015 (previously presented, defined here as “Period 1” [P1]) and cumulative to May 2017 (updated, defined as “Period 2” [P2]). Serious adverse drug reactions (ADR; implied causality) from post-marketing sources are also summarised.
Results: Demographics at respective study enrolment, including age (36.5 years, CT3.5), proportion of females (66.3%, CT3.5) and prior disease modifying drug experience, were balanced among treatment groups. Adj-AE per 100PY rates for experiencing ≥1 serious TEAE were 3.88 (CT3.5) and 3.24 (PBO) in P2, 4.00 (CT3.5) and 3.57 (PBO) in P1. Adj-AE per 100PY for serious lymphopenia (preferred term [PT]) were 0.11 (CT3.5) and 0 (PBO) in P2, 0.12 (CT3.5) and 0 (PBO) in P1; for serious infection and infestations (system organ class [SOC]): 0.63 (CT3.5) and 0.44 (PBO) in P2, 0.69 (CT3.5) and 0.50 (PBO) in P1; for serious herpes zoster (PT): 0.05 (CT3.5) and 0 (PBO) in P2, 0.06 (CT3.5) and 0 (PBO) in P1. Adj-AE per 100PY for serious neoplasms, benign, malignant and unspecified (SOC) were 0.65 (CT3.5) and 0.35 (PBO) in P2, 0.74 (CT3.5) and 0.50 (PBO) in P1. Regarding post-marketing data, 11 serious ADRs were reported; none are new safety findings for CT3.5.
Conclusions: This integrated analysis confirms the serious TEAE profile associated with CT3.5 treatment of patients with early and active RMS. The updated profile (P2) was generally consistent with that from 2 years prior (P1). No new major safety findings were identified in the updated dataset, where patients were followed for up to 10 years.
Disclosure: The CLARITY study: NCT00213135; The CLARITY Extension study: NCT00641537; The ORACLE-MS study: NCT00725985; The PREMIERE registry: NCT01013350. Disclosures: This study was sponsored by EMD Serono Inc, a business of Merck KGaA, Darmstadt, Germany (in the USA), and Merck Serono SA, Geneva, an affiliate of Merck KGaA Darmstadt, Germany (ROW). Author disclosures
SC has received honoraria for lectures/consultations from Merck, Bayer HealthCare, Sanofi-Aventis, Neurology Reviews, Biogen Idec, Teva Pharmaceuticals, and Actinobac Biomed Inc.; has served on advisory boards for Bayer HealthCare, Merck, Actinobac Biomed, Teva Pharmaceuticals, and Biogen Idec; and received grant support from Bayer HealthCare. GG has received speaker honoraria and consulting fees from Abbvie, Atara Bio, Almirall, Bayer Schering Pharma, Biogen Idec, FivePrime, GlaxoSmithKline, GW Pharma, Merck, , 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, Novartis, and Ironwood. TL has received consultancy fees or clinical research grants from Acorda, Bayer, Biogen, Daiichi, EMD Serono, Novartis, ONO, Pfizer, Teva Neuroscience. SS is an employee of EMD Serono, Inc., a business of Merck KGaA, Darmstadt, Germany. AN and RS are employees of Merck KGaA, Darmstadt, Germany.