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KESIMPTA demonstrated efficacy in a range of MS outcome measures1–5

 

The efficacy profile of KESIMPTA compared with teriflunomide was characterised in ASCLEPIOS I and II and exploratory meta- and post hoc analyses.1–5 Median treatment duration in the ASCLEPIOS I and ASCLEPIOS II trials was 85 weeks (interquartile range: 73-97 weeks).1,2

KESIMPTA was studied in two identically designed
Phase 3 trials vs an oral active comparator (teriflunomide)2

ASCLEPIOS I and II were Phase 3, randomised, double-blind, double-dummy, active comparator-controlled, parallel-group, multicentre adaptive and flexible duration design trials (maximum duration of up to 30 months). Across both trials, median treatment duration was 85 weeks (33% of patients receiving KESIMPTA were treated for more than 96 weeks [interquartile range: 73-97 weeks]).1,2

KESIMPTA demonstrated a significant reduction in relapses of up to 59% vs teriflunomide1,2

ASCLEPIOS Primary endpoint

Relative reduction in annualized relapses vs teriflunomide

Annualized relapse rate (ARR) is the mean number of attacks experienced by a patient over 1 year

ARR=annualized relapse rate; CI=confidence interval.

*Data on the ARR were analysed using a negative binomial regression model, with an offset for time spent in the trial in years to adjust for varying treatment duration among patients.

KESIMPTA demonstrated a significant reduction in the number of gadolinium enhancing (Gd+) T1 lesions vs teriflunomide, with near complete suppression of T1 lesion activity1,2

ASCLEPIOS key MRI secondary endpoints

Mean number of Gd+ T1 lesions per MRI scan1,2

Gadolinium: a contrast agent to enhance the appearance of inflammation on an MRIT1 MRI: a T1 MRI supplies information about current disease activity by highlighting areas of active inflammation

KESIMPTA use resulted in a significant reduction in the number of new or enlarging T2 lesions, with 5x fewer new or enlarging lesions per year vs teriflunomide1,2

Mean number of new or enlarging T2 lesions per year1,2

T2 MRI: a T2 MRI provides information about the total amount of lesion area, both old and new

CI=confidence interval; Gd+=gadolinium enhancing; MRI=magnetic resonance imaging.
*Negative binomial regression model.

KESIMPTA demonstrated a significant reduction in risk of confirmed disability worsening (CDW) vs teriflunomide2

ASCLEPIOS clinical secondary endpoints

Pre-specified meta-analysis of pooled data from ASCLEPIOS I and II

3–month CDW1,2

6–month CDW1,2

CDW manifests as an increase in a patients' EDSS score that is sustained over a pre-determined time period. This was previously termed confirmed disability progression (CDP).8 CDW is reflective of the worsening of relapsing-remitting MS (RRMS) disability, whereas CDP is more often used to represent progressive changes.

KESIMPTA demonstrated a favourable trend but non-significant difference in 6-month confirmed disability improvement (CDI) vs teriflunomide†2,4

6-month CDI was defined as a decrease from baseline in EDSS score sustained for at least 6 months.2

CDI=confirmed disability improvement; CDP=confirmed disability progression; CDW=confirmed disability worsening; CI=confidence interval;
EDSS=expanded disability status scale; HR=hazard ratio; K-M=Kaplan-Meier; RRMS=relapsing-remitting multiple sclerosis.
*Indicated statistical significance (2-sided) at the 0.04875 level.
Across both trials, median treatment duration was 85 weeks (interquartile range: 73-97 weeks).1,2 Analysed via a Cox regression model. 6-month confirmed disability improvement was defined as a decrease from baseline in EDSS score sustained for at least 6 months. Statistical test uses significance (2-sided) level at 0.04875.

KESIMPTA achieved no evidence of disease activity (NEDA-3) in more patients vs teriflunomide3,5

ASCLEPIOS post hoc analysis

Post hoc analysis of pooled ASCLEPIOS I and II studies3,5

Month 0–12

Percentage of patients treated with KESIMPTA achieving individual component measures of NEDA-3

 

 

Month 12–24

Percentage of patients treated with KESIMPTA achieving individual component measures of NEDA-3

 

 

NEDA-3 is defined as no:9

Re-baselining for Year 2 (Months 12–24) was conducted at Month 12 to adjust for the impact of disease activity occurring prior to treatment initiation (T2 lesions) and continuing through the first year of treatment. This re-baselining allows for an accurate measure of the impact on disease activity as measured in Year 2.9,10

No conclusions of clinical outcomes can be drawn.
CI=confidence interval; CDW=confirmed disability worsening; Gd+=gadolinium positive; NEDA=no evidence of disease activity.

Neurofilament light chain (NfL) concentration in serum and annual rate of brain volume loss (BVL)

ASCLEPIOS additional secondary endpoints

KESIMPTA showed a significant and consistent reduction in serum NfL levels from first assessment at Month 3 vs teriflunomide*2,4

 

KESIMPTA showed no difference in the slope of brain volume change from baseline vs teriflunomide*2,4

BVL=brain volume loss; CI=confidence interval; NfL=neurofilament light chain; PBVC=percentage brain volume change.
*Based on the results of the ASCLEPIOS I and ASCLEPIOS II phase 3 pivotal trials for Kesimpta. Across both trials median treatment duration was 85 weeks (interquartile range: 73-97 weeks).1,2 Full analysis set. NfL concentration in serum was analysed via a repeated measures model. Brain volume change was analysed by a Jacob integration model, random coefficient model.

ARR=annualized relapse rate; MRI=magnetic resonance imaging; MS=multiple sclerosis; NEDA-3=no evidence of disease activity.

References

  1. KESIMPTA [Summary of Product Characteristics]. Basel, Switzerland: Novartis AG; April 2021.
  2. Hauser SL, Bar-Or A, Cohen JA, et al. Ofatumumab versus Teriflunomide in Multiple Sclerosis. New Engl J Med. 2020;383:547–547.
  3. Hauser SL, Bar-Or A, Cohen JA, et al. Ofatumumab vs Teriflunomide in Relapsing Multiple Sclerosis: Analysis of No Evidence of Disease Activity (NEDA-3) from ASCLEPIOS I and II Trials [Poster LB62]. Presented at: 6th EAN Congress as Virtual Congress; 23–26 May 2020.
  4. Hauser SL, Bar-Or A, Cohen J, et al. Efficacy and safety of ofatumumab versus teriflunomide in RMS: Phase 3 ASCLEPIOS I and II trials. Presented at: 25th ECTRIMS Congress; September 2019; Stockholm, Sweden.
  5. Data on file. OMB157 (ofatumumab). Summary of clinical efficacy in relapsing multiple sclerosis. Novartis Pharmaceuticals Corp; East Hanover, NJ. December 2019.
  6. Kesimpta (ofatumumab). Managing Frequently Asked Questions (FAQs) and Potential Objections.
  7. Fox EJ, Mayer L, Aungst A, et al. Long-term safety, compliance, and effectiveness of ofatumumab in patients with relapsing multiple sclerosis: The ALITHIOS Phase 3b study [Poster P0218]. Poster presented at: 8th Joint ACTRIMS-ECTRIMS Meeting, MS Virtual 2020; 11–13 September 2020.
  8. Giovannoni G, Tomic D, Bright JR, Havrdová E. “No evident disease activity”: The use of combined assessments in the management of patients with multiple sclerosis. Mult Scler. 2017;23(9):1179–1187.
  9. Data on file. OMB157 (ofatumumab). OMB 157G 5.3.5.3. Statistical overview. Novartis Pharmaceuticals Corp; East Hanover, NJ. December 2019.
  10. Giovannoni G, Turner B, Gnanapavan S, et al. Is it time to target no evident disease activity (NEDA) in multiple sclerosis? Mult Scler Relat Disord. 2015;4(4):329–333.
UK | March 2021 | 108314
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