February 2, 2026
Finance

Sanofi Advances Venglustat Regulatory Plans Amid Mixed Trial Findings for Rare Diseases

New phase 3 results for venglustat in type 3 Gaucher and Fabry diseases show promise with some setbacks, guiding regulatory strategy

Summary

Sanofi has released new data from its LEAP2MONO phase 3 trial comparing oral venglustat to enzyme replacement therapy (ERT) in patients 12 and older with type 3 Gaucher disease. The investigational drug met the primary endpoint and most secondary endpoints in neurological manifestations and showed comparable results to ERT on non-neurological measures. However, data from another phase 3 study for Fabry disease did not meet its primary endpoint, resulting in ongoing analysis. Sanofi plans regulatory submissions for venglustat in Gaucher disease and continues evaluation in Fabry disease while monitoring safety and efficacy.

Key Points

Venglustat met the primary endpoint and three of four key secondary endpoints in type 3 Gaucher disease patients aged 12 and older with neurological symptoms.
In non-neurological measures such as spleen and liver volume and hemoglobin levels, venglustat performed similarly to enzyme replacement therapy (ERT).
Sanofi plans to submit global regulatory applications for venglustat in GD3 based on positive phase 3 data.
Phase 3 trials for venglustat in Fabry disease showed pain reduction in both arms but did not meet the primary endpoint; further analysis is ongoing.

Sanofi SA (NASDAQ:SNY) recently disclosed topline findings from its LEAP2MONO phase 3 clinical trial assessing venglustat's efficacy as a once-daily oral therapy against the current standard intravenous enzyme replacement therapy (ERT) administered biweekly in patients aged 12 and older diagnosed with type 3 Gaucher disease (GD3).

Venglustat functions as an investigational glucosylceramide synthase inhibitor, aiming to mitigate the pathological buildup of certain sugars and fat molecules in cellular and organ tissues. Importantly, this compound is designed to cross the blood-brain barrier, a key attribute considering the neurological involvement in GD3.

In the randomized trial, 43 participants were assigned to one of two groups: one receiving venglustat with a placebo infusion, and the other receiving standard ERT alongside a placebo tablet. The study's primary goal was to determine if venglustat could match or surpass the efficacy of ERT in managing neurological symptoms associated with GD3.

The trial results indicated that venglustat met its primary endpoint and achieved three out of four key secondary endpoints relating to neurological manifestations in both adolescent and adult cohorts with GD3. When examining non-neurological outcomes—specifically changes in spleen volume, liver volume, and hemoglobin levels—venglustat's performance paralleled that of ERT, meeting the study's secondary objectives.

Based on these data, Sanofi intends to move forward with global regulatory submissions to seek approval for venglustat in treating type 3 Gaucher disease.

Separately, venglustat is under investigation for Fabry disease, another rare lysosomal storage disorder. Preliminary results from the phase 3 PERIDOT trial demonstrated reductions in neuropathic and abdominal pain across both treatment arms; however, the study did not achieve its primary endpoint. Sanofi is conducting additional data analyses to further understand these findings. Additionally, the ongoing CARAT phase 3 trial is evaluating venglustat's impact on left cardiac ventricular mass index among male and female Fabry disease patients.

Throughout clinical evaluations, venglustat has shown an acceptable tolerability profile with no emergent safety concerns relative to previous studies.

Sanofi's current portfolio includes ERT products such as Fabrazyme for Fabry disease and both Cerezyme and Cerdelga for Gaucher disease, available in multiple markets worldwide. Notably, the FDA expanded Cerezyme's label in January 2026 to cover non-central nervous system manifestations of GD3, augmenting its prior approval for GD1 treatment in the United States.

The LEAP2MONO study remains ongoing, with further findings expected following completion of its open-label phase.

At the time of this announcement, Sanofi's stock (SNY) exhibited a 1.28% increase in premarket trading, valued at $47.64 per share.

Risks
  • The phase 3 PERIDOT study in Fabry disease failed to meet its primary endpoint, indicating uncertain efficacy in this indication.
  • Ongoing analysis of Fabry disease trial data may reveal limitations or unexpected findings affecting regulatory prospects.
  • The LEAP2MONO trial is still ongoing with open-label data pending, so long-term efficacy and safety remain to be fully characterized.
  • No new safety signals emerged, but longer-term safety surveillance is necessary given the investigational status of venglustat.
Disclosure
Education only / not financial advice
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