Abstract Details

Title Ponesimod Shows Improved Effect on Brain Volume Compared with Other DMTs, A Model Based Meta-Analysis

Topic Multiple Sclerosis

Presentation(s) P1 - Poster Session 1 (9:00 AM-5:00 PM)

Poster/Presentation
Number 291

Objective In the Phase Ill OPTIMUM study, treatment with ponesimod (20 mg) has shown less brain atrophy from baseline to Week 108 compared with teriflunomide (14 mg). Here we model and evaluate Brain Volume Loss (BVL) across randomized clinical trials (RCTs).

Background BVL can be seen in the earliest stages of multiple sclerosis (MS) and may lead to irreversible neurological impairment. MS Disease Modifying Therapies (DMTs) effects on BVL have been investigated in RCT settings.

Design/Methods A model-based meta-analysis (MBMA) of published RCTs of patients with Relapsing-Remitting MS was performed to indirectly compare ponesimod with other DMTs, in terms of BVL. The MBMA used longitudinal change from baseline brain volume and assumed that treatment effect vs. placebo changed over time with an exponential function. A nonparametric placebo approach was utilized to estimate relative treatment effects and reduce potential bias from between-trial heterogeneity in absolute BVL.

Results The MBMA included longitudinal BVL data from 21 eligible RCTs that investigated 11 unique drugs and placebo. Based on indirect comparison, ponesimod appears to lead to less BVL at 2 years compared with placebo and 10 other comparators, including other sphingosine 1-phosphate (S1P) receptor modulators, orals and anti-CD20 B cell depleting monoclonals. The median difference in % brain volume loss at 2 years [95% Cl] ranged from 0.23 [0.04 -0.42] to 0.78 [0.58 -1.03].

Conclusions Based on the MBMA results, ponesimod, the only monospecific S1P1 receptor modulator, has shown improved brain volume data compared to other MS DMTs. Additional studies looking at direct CNS effects of ponesimod could help to further explain its beneficial effect on BVL.

Authors/Disclosures
Maria Ait Tihyaty (Johnson and Johnson Innovative Medicine) PRESENTER	Dr. Ait Tihyaty has received personal compensation for serving as an employee of Dianthus Therapeutics.
	No disclosure on file
Alexander Keenan	Alexander Keenan has received personal compensation for serving as an employee of Janssen Pharmaceuticals. Alexander Keenan has received stock or an ownership interest from Johnson and Johnson.
	No disclosure on file

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