Svar Life Science

May 12, 2023

First-in-human study with SAR445088: A novel selective classical complement pathway inhibitor

NEW Complement solutions  CITATION

In this new study, WIESLAB® Complement System Classical Pathway (CP) and WIESLAB® Complement System Alternative Pathway (AP) assays were used to determine the pharmacodynamic profile of SAR445088 in the first-in-human trial of this anti-C1s humanized monoclonal antibody. 

According to the study, SAR445088 was well-tolerated and had variable pharmacokinetic (PK) and pharmacodynamic (PD) profiles after ascending doses and multiple doses in humans.

May 12, 2023

First-in-human study with SAR445088: A novel selective classical complement pathway inhibitor

NEW Complement solutions  CITATION

In this new study, WIESLAB® Complement System Classical Pathway (CP) and WIESLAB® Complement System Alternative Pathway (AP) assays were used to determine the pharmacodynamic profile of SAR445088 in the first-in-human trial of this anti-C1s humanized monoclonal antibody. 

According to the study, SAR445088 was well-tolerated and had variable pharmacokinetic (PK) and pharmacodynamic (PD) profiles after ascending doses and multiple doses in humans.

BACKGROUND AND STUDY OBJECTIVES

SAR445088 is an anti-C1s humanized monoclonal antibody that inhibits activated C1s, preventing the enzymatic action of C1 on its substrates. Thus SAR445088 inhibits the Complement classical pathway, whereas the alternative pathway and lectin pathways remain functional.

This publication reports the first-in-human single-center, double-blind, randomized, placebo-controlled, integrated single ascending dose (part 1) and multiple ascending doses (part 2) studies of SAR445088.

This study assessed the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of SAR445088 in healthy participants. 

The WIESLAB CP was used to determine the activity of SAR445088 by quantitatively determining complement activation in serum. Furthermore, the WIESLAB AP was used to determine retained functional complement AP in human serum. 

STUDY OUTCOMES

Utilizing the WIESLAB CP as one of two methods to determine PD. A dose-dependent inhibition of percent CP activity is reported after single or multiple doses. The extent and duration of inhibition of percent CP activity appeared to be dose-dependent. 

In this first-in-human trial, SAR445088 was well tolerated. No serious AE occurred, and a dose-dependent inhibition was demonstrated. This supports further evaluation of SAR445088 in patients with classical complement-mediated diseases such as cold agglutinin disease, chronic inflammatory demyelinating polyneuropathy (CIDP), and antibody-mediated rejection (AMR) of organ transplants.

We at Svar think that this is an exciting progression in pathway-specific complement modulation, Paving the way for further studies with similar approaches.

CITATION

Chow T, et al., First-in-human study with SAR445088: A novel selective classical complement pathway inhibitor. Clin Transl Sci. (2023) DOI: 10.1111/cts.13481

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