EMD Serono, Inc., USA (an affiliate of Merck KGaA, Darmstadt, Germany)

Author Of 2 Presentations

Disease Modifying Therapies – Mechanism of Action Poster Presentation

P0310 - Cladribine tablets in patients with RRMS and active SPMS after suboptimal response to prior DMD (MASTER-2 and CLICK-MS): initial baseline demographics (ID 129)

Speakers
Presentation Number
P0310
Presentation Topic
Disease Modifying Therapies – Mechanism of Action

Abstract

Background

Although the efficacy and safety of cladribine tablets (CT) 10 mg (3.5 mg/kg cumulative dose over 2 years [yrs]) have been shown in patients (pts) with relapsing forms of multiple sclerosis (MS) in Phase 3 trials, real world data are limited.

Objectives

To examine real-world effectiveness, safety, and pt reported outcomes (PROs) in pts with relapsing-remitting MS (RRMS) and active secondary progressive MS (SPMS) who transition to CT after suboptimal response to prior disease-modifying drugs (DMDs).

Methods

MASTER-2 and CLICK-MS are single arm, observational, 30-month (mo), Phase 4 trials in the US (Timeline: 2019–2023). Eligible pts are adults with RRMS or active SPMS, with suboptimal response to an oral/infusion (MASTER-2) or injectable (CLICK-MS) DMD, meeting criteria for CT 3.5 mg/kg treatment (US Prescribing Information). The primary outcome is 24-mo annualized relapse rate (ARR). Key secondary outcomes are PROs, treatment adherence and satisfaction, ARR in prior 24 mos, MS treatment pattern prior to transition and follow-up if CT are discontinued, and adverse events (AEs). Planned enrollment per study is 200 pts across 50 sites.

Results

Pt enrollment is ongoing for both trials. As of May 2020, 52 pts (mean [standard deviation {SD}] age: 50 [10.6] yrs; 75% female) have baseline data available in MASTER-2 (data not shown for CLICK-MS). Mean (SD) time since diagnosis was 11.8 (7.71) yrs. Most recent DMDs used included teriflunomide (23.1%), dimethyl fumarate (23.1%), fingolimod (19.2%), ocrelizumab (13.5%), natalizumab (9.6%) and alemtuzumab (1.9%). Sixteen pts had 21 relapses within 24 mos prior to enrollment (mean [SD] ARR: 0.21 [0.351]). Mean (SD) baseline PRO scores before starting CT were 50.7 (25.11) for 14-Item Treatment Satisfaction Questionnaire for Medication (Global Satisfaction), 50.0 (9.57) and 41.4 (11.56) for 36-Item Short Form Health Survey (mental and physical component summaries, respectively), 1.4 (1.71) for Beck-Depression Inventory-Fast Screen, 8.9 (4.79) for the Fatigue Impact Scale, and 2.7 (2.31) for Patient Determined Disability Steps scale. Thirty-six treatment emergent AEs (2 serious, but unrelated) were seen in 12 pts in 9.97 pt-yrs to date. Additional MASTER-2 and CLICK-MS pt baseline data will be shown in the presentation.

Conclusions

These studies will report real-world effectiveness and safety data of cladribine tablets in pts with RRMS and active SPMS with suboptimal response to prior oral, infusion, or injectable DMDs.

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Disease Modifying Therapies – Risk Management Poster Presentation

P0411 - Treatment-emergent adverse events occurring early in the treatment course of cladribine tablets in two phase 3 trials in multiple sclerosis (ID 377)

Speakers
Presentation Number
P0411
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

Tolerability and adherence to disease-modifying drugs (DMDs) can be influenced by treatment-emergent adverse events (TEAEs) that start shortly after therapy initiation. One potential advantage of cladribine tablets is its short treatment course which may limit TEAEs; patients who receive the approved 3.5 mg/kg dosage only receive doses for two 4 to 5-day periods per treatment year.

Objectives

To identify TEAEs early in the course of treatment in patients enrolled in the Phase 3 CLARITY and ORACLE-MS clinical trials.

Methods

This was a post hoc analysis of safety populations in CLARITY and ORACLE-MS studies. Patients received cladribine tablets 3.5 mg/kg (cumulative dose over 2 years; N=636) or placebo (N=641). The incidence of early adverse events, TEAEs, serious TEAEs, drug-related TEAEs, and TEAEs leading to discontinuation were summarized based on incidence within 2, 6, and 12 weeks (Wk) after commencement of therapy.

Results

The incidence of TEAEs occurring within the first 2–12Wk of treatment across both trials in both treatment groups was generally low, and the majority of events were mild (placebo: 53.8–68.4%; cladribine tablets: 54.4–68.0%). The most common TEAEs by time epoch after initiating placebo and cladribine tablets 3.5 mg/kg treatment, respectively, were: nausea: 3.3% vs. 4.9% (2Wk), 3.7% vs. 6.4% (6Wk), and 4.5% vs. 8.0% (12Wk); fatigue: 2.0% vs. 1.4% (2Wk), 3.1% vs. 2.5% (6Wk), and 4.4% vs. 3.1% (12Wk); headache: 8.3% vs. 9.0% (2Wk), 11.9% vs. 14.8% (6Wk), and 15.1% vs. 18.4% (12Wk); lymphopenia: 0.0% vs. 2.5% (6Wk) and 0.5% vs. 6.8% (12Wk); leukopenia: 0.0% vs. 1.3% (12Wk). Other endpoints will be shown in the final presentation.

Conclusions

Incidence of TEAEs experienced during the first 12 weeks of treatment with cladribine tablets 3.5 mg/kg in Phase 3 clinical trials was low and mostly mild. Nausea, headache, and lymphopenia were seen more frequently in cladribine tablets-treated patients versus those in the placebo group. These findings suggest that cladribine tablets are generally well tolerated, which may facilitate treatment adherence.

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