Rilzabrutinib Granted Orphan Drug Designation For Multiple Rare, Immune-Mediated Conditions

Rilzabrutinib (Sanofi), an investigational, novel, advanced, oral, reversible Bruton’s tyrosine kinase (BTK) inhibitor, was granted orphan drug designation (ODD) by the FDA for the treatment of warm autoimmune hemolytic anemia (wAIHA) and IgG4-related disease (IgG4-RD), according to a news release from Sanofi.¹

Anemia can present in mutltiple forms and necessitate frequent transfusions and visits to a clinician. | Image Credit: © Elnur - stock.adobe.com

Neither wAIHA nor IgG4-RD has any currently approved treatments for patients, presenting a major unmet medical need for those who struggle with either of these rare diseases. FDA ODD is designed to bolster research into investigational therapies that address rare diseases or conditions affecting fewer than 200,000 patients in the US. Previously, rilzabrutinib received fast track designation for the treatment of immune thrombocytopenia (ITP); with a Prescription Drug User Fee Act (PDUFA) date of August 29, 2025, for its ITP designation, rilzabrutinib is poised to become a standard care option for ITP, wAIHA, IgG4-RD, and other immune-mediated diseases.²

Supporting clinical trial from phase 2 trials demonstrated the potential effectiveness of rilzabrutinib in each of the 2 conditions indicated for the ODD. For wAIHA, data from a phase 2b study (NCT05002777) were presented at the American Society of Hematology 2024 Annual Meeting and Exposition, highlighting rilzabrutnib’s clinically meaningful outcomes on disease markers and response rate in patients with the disease. An overall hemoglobin response was achieved in 14 of 22 enrolled patients (64%), with increased hemoglobin levels associated with reduced hemolysis markers. There were no serious treatment-related adverse events, according to investigators.^3,4

Regarding IgG4-RD, the results of a phase 2a trial (NCT04520451) found that 52 weeks of treatment with rilzabrutinib led to a reduction in disease flare-ups, glucocorticoid sparing, and other disease markers, with a positive safety profile consistent with previous studies. Investigators from Sanofi said that detailed data from this trial will be presented at an upcoming medical meeting.^1,5

“ODD for these 2 rare, immune-mediated conditions validates our ongoing commitment to pursuing potential first- and best-in-class medicines for diseases that affect small populations but persist with unmet medical need,” Karin Knobe, MD, PhD, global head of development, rare diseases, at Sanofi, said in the news release. “Our continued exploration of rilzabrutinib across multiple indications speaks to our belief in its potential for multi-immune modulation.”¹

In conjunction with new Tailored Covalency technology from Sanofi, rilzabrutinib is designed to selectively inhibit the BTK target in B-cells and other immune cells, which plays an essential role in inflammation and the pathogenesis of multiple immune-mediated diseases. While rilzabrutnib selectively inhibits BTK, it is intended to simultaneously reduce the risk of off-target side effects. Patients with wAIHA or IgG4-RD face debilitating symptoms of their conditions; both diseases can be fatal, especially IgG4-RD, which impacts almost every organ and leads to sometimes irreversible organ dysfunction. Rilzabrutinib is poised to transform the treatment paradigm for these patients, offering them new hope for these previously treatment-less conditions.¹

As mentioned previously, rilzabrutinib demonstrated meaningful results in the phase 3 LUNA trial in adults with persistent or chronic ITP, another rare, immune-mediated disease. Across the study population, 65% of patients receiving rilzabrutinib reported a platelet response, compared with 33% of patients on placebo. Given the similarities in pathology between ITP and wAIHA—both conditions are characterized by bleeding and the risk of thrombosis episodes—these positive results from LUNA provide positive indications for the future of rilzabrutinib’s development in wAIHA.^1,6

REFERENCES

1. Sanofi. Press release: Rilzabrutinib granted orphan drug designation in the US for two rare diseases with no approved medications. News Release. Released April 3, 2025. Accessed April 4, 2025. https://www.sanofi.com/en/media-room/press-releases/2025/2025-04-03-05-00-00-3054815

2. Rosa K. Rilzabrutinib gets FDA fast track designation for immune thrombocytopenia. Pharmacy Times. Published November 19, 2020. Accessed April 4, 2025. https://www.pharmacytimes.com/view/rilzabrutinib-gets-fda-fast-track-designation-for-immune-thrombocytopenia

3. Cooper N, Kuter DJ, Frederiksen H, et al. 3836 Part a Efficacy and Safety of Oral Bruton Tyrosine Kinase Inhibitor (BTKi) Rilzabrutinib in Patients with Warm Autoimmune Hemolytic Anemia (wAIHA): Multicenter, Open-Label, Phase 2b Study. Presented at ASH Annual Meeting & Exposition Monday, December 9, 2024. Accessed Online April 4, 2025. https://ash.confex.com/ash/2024/webprogram/Paper200325.html

4. ClinicalTrials.gov. Efficacy, Safety and Pharmacokinetics of Rilzabrutinib in Patients With Warm Autoimmune Hemolytic Anemia (wAIHA) (LUMINA 2). National Library of Medicine. Last Updated February 28, 2025. Accessed April 4, 2025. https://clinicaltrials.gov/study/NCT05002777

5. ClinicalTrials.gov. Open Label Two-Arm Study to Evaluate Rilzabrutinib in IgG4-Related Disease Participants. National Library of Medicine. Last Updated February 21, 2025. Accessed April 4, 2025. https://www.clinicaltrials.gov/study/NCT04520451?tab=results

6. Sanofi. Press release: ASH: Rilzabrutinib demonstrated significant patient benefit in the first positive phase 3 study of a BTK inhibitor in ITP. News Release. Released December 7, 2024. Accessed April 4, 2025. https://www.sanofi.com/en/media-room/press-releases/2024/2024-12-07-16-30-00-2993342