Pivotal Trial Data

Phase 3 study results: Respectively for each trial, results for the primary end point: reduction of ARR, 51% (0.11 vs 0.22), 58% (0.10 vs 0.25); for the key secondary end points: reduction of number of Gd+ T1 lesions per scan, 98% (0.01 vs 0.46), 94% (0.03 vs 0.52); reduction of annualized rate of NE T2 lesions, 82% (0.72 vs 4.00), 85% (0.64 vs 4.16); 3-month CDP risk reduction of 34% (10.9 vs 15.0).¹

ASCLEPIOS I & II study design: ASCLEPIOS I and II were 2 identical, randomized, active-controlled, double-blind Phase 3 studies in patients with relapsing MS, approximately 40% of whom were DMT treatment naïve. Patients were randomized to double-dummy SC KESIMPTA (20 mg every 4 weeks) or oral Aubagio (14 mg daily) for up to 30 months. Primary end point was ARR. Key end points were number of Gd+ T1 lesions and annualized rate of new or enlarging T2 lesions, and reduction in risk of 3-month CDP. Treatment duration was variable based on end of study criteria. Maximum duration 120 weeks, median duration 85 weeks.¹

ARR reductions³

Limitations: This analysis represents chance findings. The open-label extension study is not blinded, not controlled, and includes inherent self-selection bias for remaining in the trial. This study is an ongoing trial and the data presented are an interim analysis. No conclusions of statistical or clinical significance can be drawn.

ALITHIOS study design: ALITHIOS (N=1703) is an open-label, umbrella extension, Phase 3b, single-arm study evaluating long-term (up to 6 years) safety, tolerability, and effectiveness of KESIMPTA (20 mg SC) in subjects with RMS. The study enrolled 1367 RMS patients from the ASCLEPIOS I and II trials who continued KESIMPTA treatment. A long-term (up to 6 years) analysis (n=465) was conducted to evaluate efficacy in the recently diagnosed treatment-naïve subgroup treated with KESIMPTA. 366/465 (78.7%) of treatment-naïve patients were still receiving KESIMPTA at data cutoff (September 25, 2023). A long-term (up to 6 years) safety analysis was conducted to evaluate IgM/IgG levels and their association with serious infection. 1330/1703 (77.6%) of patients were still receiving KESIMPTA at data cutoff (September 25, 2023).^3-6

*Treatment-naïve was defined as patients not on any treatment prior to starting the clinical trials. This includes patients who started on KESIMPTA and patients who switched from teriflunomide to KESIMPTA.⁴

Long-term MRI lesion activity in patients who remained on KESIMPTA and those who switched from Aubagio to KESIMPTA

T1 Lesions Over Time³

T2 Lesions Over Time³

Limitations: This analysis represents chance findings. The open-label extension study is not blinded, not controlled, and includes inherent self-selection bias for remaining in the trial. No conclusions of statistical or clinical significance can be drawn.

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ARR reductions in treatment-naïve patients on first-line KESIMPTA vs Aubagio

Primary end point: relative reduction in annualized relapses vs Aubagio⁷

Gd+ T1 lesions reductions up to 6 years⁴

NE T2 lesions reductions up to 6 years⁴

This post hoc study assessed the benefit–risk profile of KESIMPTA vs Aubagio, comprising clinical and MRI data in a subpopulation of recently diagnosed treatment-naïve participants from the combined ASCLEPIOS I and II trial populations.⁷

Post hoc study design: Efficacy and safety data were drawn from the pooled ASCLEPIOS subpopulation of protocol-defined treatment-naïve patients who were within 0.1–2.9 years from diagnosis (median 0.35 and 0.36 years for KESIMPTA and Aubagio patients, respectively). Of the 1882 participants randomly assigned to treatment in ASCLEPIOS I and II, 615 (32.7%) were both recently diagnosed and treatment naïve at baseline (KESIMPTA, 314; Aubagio, 301).⁷
No conclusions can be drawn.

ALITHIOS study design: ALITHIOS (N=1703) is an open-label, umbrella extension, Phase 3b, single-arm study evaluating long-term (up to 6 years) safety, tolerability, and effectiveness of KESIMPTA (20 mg SC) in subjects with RMS. The study enrolled 1367 RMS patients from the ASCLEPIOS I and II trials who continued KESIMPTA treatment. A long-term (up to 6 years) analysis (n=465) was conducted to evaluate efficacy in the recently diagnosed treatment-naïve subgroup treated with KESIMPTA. 366/465 (78.7%) of treatment-naïve patients were still receiving KESIMPTA at data cutoff (September 25, 2023). A long-term (up to 6 years) safety analysis was conducted to evaluate IgM/IgG levels and their association with serious infection. 1330/1703 (77.6%) of patients were still receiving KESIMPTA at data cutoff (September 25, 2023).^3-6

^†As evidenced by ARR, MRI (Gd+ T1 and T2 lesions), and 3- and 6-month CDP. Primary end point, ARR reduction of 51% (0.11 vs 0.22), 58% (0.10 vs 0.25).^1
‡KESIMPTA Sensoready® Pens must be refrigerated at 2°C to 8°C (36°F to 46°F). Keep product in the original carton to protect from light until the time of use. Do not freeze. To avoid foaming, do not shake. If necessary, KESIMPTA may be stored at room temperature below 30°C (86°F) for up to 7 days and returned to the refrigerator, to be used within the next 7 days.¹

NEDA-3 status at year 6 was similar for participants regardless of previous DMT experience before entry in the trials.^3,4

Re-baselining for year 2 (months 12-24) was conducted at month 12 to adjust for impact of disease activity prior to treatment initiation (T2 lesions) and continuing through the first year of treatment. This re-baselining allows for the accurate measure of the disease activity as measured in year 2.^9,10

Limitations: This analysis considers patients without evidence of disease activity (which may also include patients with partially missing information) as NEDA-3. A sensitivity analysis was conducted for the population of patients who completed the full 24 months of treatment.⁹ No conclusions of clinical outcomes can be drawn.

NEDA-3 post hoc analysis design: All patients from the pivotal trials, full analysis set population (all randomized patients with assigned treatments) who also received KESIMPTA in the ALITHIOS extension study (data cutoff: September 25, 2023) were included in the intent-to-treat principle, but patients who discontinued from the study drug prematurely for reasons other than “lack of efficacy” or “death” and had NEDA-3 before early discontinuations were excluded. The outcomes presented here are the proportion of study patients within a treatment group who met the NEDA-3 criteria vs those who did not. The proportion of patients meeting NEDA-3 criteria was analyzed cross-sectionally in 1-year time intervals across 6 years. Within the prespecified time period, patients who achieved NEDA-3 experienced no 6-month CDP; no confirmed relapse; no Gd+ T1 lesions; no NE T2 lesions; and no discontinuation from the study drug due to either lack of efficacy or death.^3,4,9
 

*Sample program is only available to patients who are determined to be appropriate candidates for treatment with KESIMPTA and is intended to give patients a chance to see if KESIMPTA may be right for them.

Risk reduction in CDP at year 6 with KESIMPTA vs later switch

6-month CDP in first-line subgroup vs later switch*

CDP (Long-term)

This post hoc study assessed the benefit–risk profile of KESIMPTA vs Aubagio, comprising clinical and MRI data in a subpopulation of recently diagnosed treatment-naïve participants from the combined ASCLEPIOS I and II trial populations. 

Limitations: This analysis represents chance findings. The open-label extension study is not blinded, not controlled, and includes inherent self-selection bias for remaining in the trial. This study is an ongoing trial and the data presented are an interim analysis. No conclusions of statistical or clinical significance can be drawn. 

Post hoc study design: Efficacy and safety data were drawn from the pooled ASCLEPIOS subpopulation of protocol-defined treatment-naïve patients who were within 0.1–2.9 years from diagnosis (median 0.35 and 0.36 years for KESIMPTA and Aubagio patients, respectively). Of the 1882 participants randomly assigned to treatment in ASCLEPIOS I and II, 615 (32.7%) were both recently diagnosed and treatment naïve at baseline (KESIMPTA, 314; Aubagio, 301).⁷
No conclusions can be drawn. 

ALITHIOS study design: ALITHIOS (N=1703) is an open-label, umbrella extension, Phase 3b, single-arm study evaluating long-term (up to 6 years) safety, tolerability, and effectiveness of KESIMPTA (20 mg SC) in subjects with RMS. The study enrolled 1367 RMS patients from the ASCLEPIOS I and II trials who continued KESIMPTA treatment. A long-term (up to 6 years) analysis (n=465) was conducted to evaluate efficacy in the recently diagnosed treatment-naïve subgroup treated with KESIMPTA. 366/465 (78.7%) of treatment-naïve patients were still receiving KESIMPTA at data cutoff (September 25, 2023). A long-term (up to 6 years) safety analysis was conducted to evaluate IgM/IgG levels and their association with serious infection. 1330/1703 (77.6%) of patients were still receiving KESIMPTA at data cutoff (September 25, 2023).^3-6

Disability progression was defined as an increase in EDSS of at least 1.5, 1, or 0.65 points in patients with a baseline EDSS of 0, 1 to 5, or 5.5 or greater, respectively. 
*Cumulative 6-month CDP event rate in first-line subgroup vs later switch. Core HR: 0.56 (0.33-0.96), P=0.035. Core + extension at 72 weeks, P=0.033.^4
†Switching period refers to the patients started with Aubagio and not applicable to the patients treated with KESIMPTA in the core period; for Aubagio/KESIMPTA group, data from first dose of Aubagio until last dose of KESIMPTA plus 100 days/analyses cutoff dates have been used.