Frexalimab (SAR441344) as a potential multiautoimmune disorder tackling mAB targeting the CD40-CD40L pathway undergoing clinical trials: a review

Abstract

Autoimmune disorders exhibit intricate pathology. Their mechanisms are complex, which attenuates the need for novel therapeutic interventions. Frexalimab, a potent monoclonal antibody targeting the dysregulated CD40-CD40L pathway, stands out as a formidable weapon against the assault of inflammation and tissue devastation. Diverse electronic databases were searched using relevant keywords to extract data on the role of Frexalimab in combating various autoimmune diseases. This review highlights Frexalimab's efficacy in improving various disability indicators of relapsing multiple sclerosis (RMS), alleviating fatigue in primary Sjögren's syndrome (PSJS), and improving glycemic control in diabetic patients. Across multiple trials, its favorable safety profile has proven its superiority over first-generation drugs in minimizing side effects. Indeed, Frexalimab has become a harbinger of hope in the fight against autoimmune diseases and has pioneered a unique and unchallenging way for tackling complex autoimmune diseases in the clinical realm, however, further large-scale trials are needed to establish its therapeutic benefits across different autoimmune conditions.

Keywords: CD40-CD40L pathway; Sjögren’s syndrome; autoimmune disorders; clinical trials; efficacy; frexalimab; multiple sclerosis; pharmacodynamics; pharmacokinetics; safety; systemic lupus erythematosus; type 1 diabetes.

Figure 1

The figure demonstrates the proposed mechanism of action of anti-CD40L monoclonal antibodies and how they further contribute towards the amelioration of symptoms in various autoimmune disorders. Normally, activation of T cells by antigen-presenting cells (APCs)/B cells requires the interaction of costimulatory molecules and the subsequent activation of the T cell receptor (TCR) signal. Anti-CD40L mAbs prevent this interaction and the downstream signaling. APC, antigen presenting cell; TCR, T-cell receptor; MHC II, major histocompatibility complex class II; mAb, monoclonal antibody.

Figure 2

Efficacy and safety profile of first generation anti-CD40L drugs (ruplizumab and toralizumab) compared with that of second generation anti-CD40L drugs (dapirolizumab pegol, letolizumab, dozadalibep, and frexalimab).