Abstract Details

Title Updated safety of cladribine tablets in the treatment of patients with multiple sclerosis: Integrated safety analysis and post-approval data

Topic Multiple Sclerosis

Presentation(s) P7 - Poster Session 7 (5:30 PM-6:30 PM)

Poster/Presentation
Number 9-017

Objective To provide an update to the previously reported treatment-emergent adverse event (TEAE) profile for cladribine tablets (CT) using the latest integrated safety data from clinical studies including final data from the PREMIERE registry, and report post-approval safety data from Europe.

Background Pooling of long-term safety data for integrated analysis from the clinical trial program allows comprehensive characterization of the CT 10 mg (3.5 mg/kg cumulative dose over 2 years [CT3.5]) safety profile in patients with relapsing multiple sclerosis (RMS).

Design/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 summarized.

Results Demographics at first dosing date were balanced among treatment groups: mean age (CT3.5=37.8 years; PBO=37.2 years); proportion of females (CT3.5=66.3%; PBO=66.1%); and patients with prior disease modifying drug experience (CT3.5=19.9%; PBO=20.4%). Incidences per 100PY for: ≥1 serious TEAE were 3.80 (CT3.5) and 3.05 (PBO); serious lymphopenia (preferred term [PT]) were 0.10 (CT3.5) and 0 (PBO); serious infections and infestations (system organ class) were 0.60 (CT3.5) and 0.42 (PBO) (serious herpes zoster [PT]: 0.05 [CT3.5] and 0 [PBO]); malignant tumors were 0.26 (CT 3.5) and 0.12 (PBO). The Periodic Benefit-Risk Evaluation Report reported 922 post-approval ADRs, including 136 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, further establishes the safety profile of CT3.5 in RMS patients, which is consistent with the previously published integrated safety analysis. No new major safety findings were identified in this latest dataset. The pattern of post-approval ADRs was consistent with the clinical safety profile for CT3.5.

Authors/Disclosures
Gavin Giovannoni, MD (QMUL) PRESENTER	Dr. Giovannoni has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck KGaA. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche-Genentech. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Moderna. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sandoz. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Astoria Biologica. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zenas. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Giovannoni has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Medscape.
Stuart D. Cook, MD, F�鶹��ýӳ�� (Rutgers)	No disclosure on file
Thomas Leist, MD, PhD, F�鶹��ýӳ�� (Thomas Jefferson University)	Dr. Leist has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Leist has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Leist has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. Dr. Leist has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. Dr. Leist has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Horizon. Dr. Leist has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech. Dr. Leist has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Leist has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen. Dr. Leist has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Genentech. Dr. Leist has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Sanofi. Dr. Leist has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Horizon. Dr. Leist has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for EMD Seono. Dr. Leist has received personal compensation in the range of $10,000-$49,999 for serving as a Expert Wittness with DHHS HRSA.
	No disclosure on file
Sana Syed, MD (Sanofi Genzyme)	Dr. Syed has received personal compensation for serving as an employee of Sanofi US.
	No disclosure on file
	No disclosure on file
	No disclosure on file

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