Rilzabrutinib for IgG4-related disease

Last updated May 30, 2025, by Lindsey Shapiro, PhD
Fact-checked by Marta Figueiredo, PhD

What is rilzabrutinib for IgG4-RD?

Rilzabrutinib is an investigational oral therapy being developed by Sanofi for people with immunoglobulin G4-related disease (IgG4-RD).

IgG4-RD arises when certain immune cells, particularly matured B-cells producing high amounts of the IgG4 antibody, infiltrate tissues and cause inflammation and scarring. Rilzabrutinib works by suppressing Bruton’s tyrosine kinase (BTK), an enzyme important for the maturation, function, and growth of B-cells and other immune cells. It is therefore expected to dampen the harmful immune responses that drive tissue damage and IgG4-RD symptoms.

Rilzabrutinib was designed with a technology that enables it to selectively and durably bind to BTK, but in a reversible way, meaning that the duration of the bond can be fine-tuned. Together, these characteristics may help prevent side effects associated with off-targets (binding to molecules other than the target) and provide a favorable long-term safety profile, in addition to high efficacy.

The experimental therapy was granted an orphan drug designation in the U.S. for IgG4-RD in 2025, a status that is meant to speed the clinical development of medications for rare diseases.

Sanofi is also investigating rilzabrutinib as a potential treatment for a number of other immune-mediated diseases.

Therapy snapshot

How will rilzabrutinib be administered in IgG4-RD?

In the single trial to date testing rilzabrutinib in IgG4-RD patients, the therapy was administered as oral tablets, at a dose of 400 mg taken twice daily.

Rilzabrutinib in IgG4-RD clinical trials

Rilzabrutinib has been tested in an international Phase 2a trial (NCT04520451) involving 27 adults with IgG4-RD.

Participants were randomly assigned to receive either rilzabrutinib plus a tapering of glucocorticoids — the standard first-line therapy for IgG4-RD that is associated with certain side effects — or glucocorticoids alone for 12 weeks (about three months). After this period, those on glucocorticoids alone were able to change to the rilzabrutinib-based regimen, and all patients continued on such treatment for up to 64 weeks (nearly 15 months).

The study’s main goals were to compare the treatments’ safety and ability to prevent flares, or periods of new or worsening symptoms.

Sanofi has reported that a year of treatment with the rilzabrutinib-based regimen led to reductions in IgG4-RD flares and other disease markers, while enabling participants to successfully taper off glucocorticoids. However, full trial results haven’t been made available yet. 

Rilzabrutinib side effects in IgG4-RD

Full results of the single trial testing rilzabrutinib in people with IgG4-RD have not been published to date, so the therapy’s side-effect profile remains unclear in this patient population.

According to Sanofi, the therapy showed a favorable safety profile in the Phase 2a trial, consistent with data from other rilzabrutinib studies involving healthy volunteers and people with other immune conditions.

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