Frexalimab shows favourable safety and efficacy in OLE

Frexalimab continued to show favourable safety and a sustained reduction in relapsing MS activity after 72 weeks in the open-label extension (OLE) of the main phase 2 trial. Lymphocyte counts were stable after 72 weeks. This data supports the further development of frexalimab in phase 3 trials as a high-efficacy, non-lymphocyte-depleting MS therapy.

Frexalimab is a second-generation IgG1 monoclonal antibody that inhibits the CD40/CD40L pathway, potentially modifying T- and B-cell activation and innate immune cell function without depleting lymphocytes [1]. In a phase 2 trial (NCT04879628), frexalimab 1,200 mg intravenous (IV) every 4 weeks was well tolerated and was associated with reduced disease activity in patients with relapsing MS. The 129 participants were randomised (4:4:1:1) to receive either frexalimab 1,200 mg IV every 4 weeks or 300 mg subcutaneous (SC) every 2 weeks, or a matching placebo. After 12 weeks, participants in the placebo groups switched to the respective frexalimab arms and entered the OLE. Prof. Gavin Giovannoni (Queen Mary University of London, UK) presented the OLE results [2].

Of the 129 participants in the randomised trial, 125 (97%) participated in the OLE; 111 (89%) were still on treatment after 72 weeks. At that time, the mean number of gadolinium-positive T1 lesions remained low, both in the group that continued on frexalimab and in the group that had switched from placebo: continued frexalimab IV, 0.1; continued frexalimab SC, 0.4; placebo IV/frexalimab IV, 0.1; placebo SC/frexalimab SC, 0.2. The mean new/enlarging T2 lesion count showed very similar patterns. T2 lesion volume also remained low, dropping below baseline values in the frexalimab IV group. The adjusted annualised relapse rate (ARR) for participants originally assigned to frexalimab IV was 0.07. In this group, 94% of the participants remained relapse-free over 72 weeks. Expanded Disability Status Scale (EDSS), lymphocyte counts, and immunoglobulin levels all remained stable. Prof. Giovannoni said the safety profile looked “very reassuring,” with no new safety signals over 72 weeks.

1. Vermersch P, et al. N Engl J Med 2024;390(7):589-600.
2. Giovannoni G, et al. Safety and efficacy of frexalimab in the treatment of relapsing multiple sclerosis: 18-month results from the phase 2 open-label extension. Abstract O066, ECTRIMS 2024, 18–20 September, Copenhagen, Denmark.

 

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Posted on 18 November 202418 November 2024