▎WuXiEdited by Kant Content Team

Today, Sanofi announced nearly one-year treatment results from the Phase 2 trial of its potential "first-in-class" monoclonal antibody frexalimab for the treatment of multiple sclerosis (MS). Analysis of the data at 48 weeks of the trial showed a continued reduction in disease activity in patients treated with frexalimab, demonstrating good tolerability.Sanofi has initiated a Phase 3 clinical trial for frexalimab in treating relapsing MS and non-relapsing secondary progressive MS.

The Phase 2 trial announced this time is a randomized, double-blind, placebo-controlled study evaluating the efficacy of frexalimab in patients with relapsing MS. Patients were randomized (4:4:1:1) to receive either high-dose (1200 mg of frexalimab intravenously every four weeks) or low-dose (300 mg of frexalimab subcutaneously every two weeks) frexalimab or a matched placebo for 12 weeks (Part A).The primary endpoint was the number of new Gd+ T1 magnetic resonance imaging (MRI) brain lesions at week 12.Secondary endpoints include other MRI-based efficacy measures as well as the safety, tolerability, and pharmacokinetics of frexalimab. After week 12, subjects receiving placebo were switched to the corresponding frexalimab group and entered Part B of the currently ongoing open-label extension (OLE).

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From the initial 12-week double-blind period, 97% (125/129) of subjects entered the OLE. The analysis results at Week 48 showed:

• At week 48, 96% and 87% of patients continuing high-dose and low-dose frexalimab treatment, respectively, showed no Gd+ T1 brain lesions.At Week 12, when the OLE began, patients who switched from placebo to high-dose and low-dose frexalimab treatment showed a reduction in Gd+ T1 brain lesions by Week 24. By Week 48, 90% and 92% of patients, respectively, did not show any Gd+ T1 brain lesions.

  
  

• The number of Gd+ T1 brain lesions in subjects continuing to receive frexalimab remained at a low level, with mean lesion counts of 0.0 (SD: 0.2) and 0.2 (SD: 0.5) in the high-dose and low-dose groups, respectively.In subjects who switched from placebo to frexalimab at week 12, the number of Gd+ T1 lesions continued to decrease, with mean lesion counts of 0.2 (SD: 0.6) and 0.1 (SD: 0.3) in the high-dose and low-dose groups, respectively.
  
  
  
  
  
• As of Week 48, the number and volume changes of new or enlarging Gd+ T2 lesions in all frexalimab treatment groups remained at low levels, and patients' lymphocyte counts remained stable.

  
  

• Subjects continuing to receive high-dose frexalimab treatment had a low annualized relapse rate (ARR) of 0.04 (95% CI: 0.01, 0.18) during the 48-week treatment period, with 96% of patients remaining relapse-free.The ARR for patients in the initial low-dose group was 0.22, while the ARR for patients switched to high-dose and low-dose frexalimab was 0.09 and 0.40, respectively, at week 48.

  
  

• Frexalimab was generally well-tolerated. In all patient subgroups receiving the therapy during the OLE period up to Week 48, the most common adverse events (≥10%) were nasopharyngitis (n=14, 11%) and headache (n=14, 11%), among others.

Frexalimab (SAR441344) is a novel CD40L-targeting monoclonal antibody believed to block the co-stimulatory CD40/CD40L cellular pathway, which is essential for the activation and function of both adaptive (T and B cells) and innate (macrophages and dendritic cells) immune cells, without the need for lymphocyte depletion.The results of the 12-week Phase 2 trial of Frexalimab for the treatment of MS have been previously published in The New England Journal of Medicine.

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References:

[1] Press Release: New 48-week frexalimab phase 2 data support potential for high sustained efficacy in multiple sclerosis. Retrieved April 17, 2024 from https://www.sanofi.com/en/media-room/press-releases/2024/2024-04-17-05-00-00-2864225

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