Sanofi is narrowing development of one of its 5 billion euro ($5.4 billion), “pipeline-in-a-product” assets. The French drugmaker axed Sjögren’s syndrome from the list of targeted indications for frexalimab after seeing phase 2 efficacy data—and reported a phase 3 flop for one of its tarnished former top prospects.
Frexalimab is a CD40L monoclonal antibody that cleared a midphase test in multiple sclerosis (MS) last year. The readout suggested Sanofi may have found a way around the blood clot risks that blighted earlier CD40 drug candidates. Encouraged, Sanofi pushed ahead with phase 3 studies in two forms of MS and midstage trials in Type 1 diabetes and systemic lupus erythematosus.
The company began comparing frexalimab, also known as SAR441344, to placebo in Sjögren’s in 2020. The goal was to show whether the candidate can improve scores on a Sjögren’s disease activity scale. Sanofi revealed the molecule fell short as part of its first-quarter results (PDF) Thursday.
“The data confirmed pharmacologic activity and well-tolerated safety profile but not the necessary efficacy outcomes to continue to move forward the development in this indication,” Sanofi said. The findings of the 84-patient phase 2 trial persuaded Sanofi to stop development in Sjögren’s. Development in other, potentially more lucrative indications is continuing.
Sanofi revealed the setback alongside news of another blow to venglustat, a GCS inhibitor that has slipped down the pecking order in recent years. Venglustat was among the assets that Paul Hudson identified as Sanofi's top prospects when he took over as CEO in 2019. However, the drugmaker stopped a phase 2/3 trial in autosomal dominant polycystic kidney disease in 2021.
The failure came months after venglustat missed the mark in a phase 2 Parkinson’s disease study. While the failures dented Sanofi’s “pipeline in a pill” ambitions, work continued in GM2 gangliosidosis, Gaucher disease type 3 and Fabry disease. Thursday, Sanofi crossed GM2 off the list of active indications “based on the absence of positive trends on clinical endpoints.”
Sanofi said the phase 3 GM2 trial “reinforced the favorable safety profile” of venglustat. Development is continuing in Fabry and Gaucher, settings in which Sanofi could file for approval in 2025 and beyond.