Riliprubart Receives FDA Orphan Drug Designation for AMR in Solid Organ Transplantation

The FDA granted an orphan drug designation (ODD) to riliprubart (SAR445088; Sanofi) for the investigational treatment of antibody-mediated rejection (AMR) in solid organ transplantation. The designation will help address a critical unmet need within transplant medicine, where AMR is a significant challenge without any FDA-approved treatments, according to a Sanofi news release.¹

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Riliprubart is a first-in-class IgG4 humanized monoclonal antibody that selectively inhibits activated C1s in the classical complement pathway of the innate immune system. The treatment’s safety and efficacy are being investigated in a phase 2 trial (NCT05156710)², which is currently ongoing, as well as the phase 3 MOBILIZE (NCT06290128)³ and VITALIZE (NCT06290141)⁴ trials.¹

According to the news release from Sanofi, the phase 2 trial is exploring riliprubart’s potential in kidney disease transplant recipients. The study includes 2 patient cohorts: those who are at risk of developing rejection (cohort A) and those with active forms of antibody-mediated rejection (cohort B). Although all patients will be treated with riliprubart, cohort A assesses the treatment’s efficacy in preventing AMR, whereas cohort B is focused on the treatment of active AMR. The multicohort, randomized, open-label trial’s primary end points are treatment failure rate (cohort A) and AMR resolution rate (cohort B), both of which will be assessed up to week 49. Additionally, secondary end points include treatment failure rate (cohort A) and AMR resolution rate (cohort B) per local assessment, and others include adverse events (AEs), pharmacokinetic measures, and changes from baseline in renal function, creatinine ratio, and histopathology.^1,2

Prior to the phase 3 MOBILIZE and VITALIZE trials, approximately 87% of participants (42/48) with chronic inflammatory demyelinating polyneuropathy (CIDP) who were treated with standard of care improved or remained stable after switching to riliprubart (52% improved). Additionally, 50% (n = 9) of those who were refractory to standard of care improved while on riliprubart. The treatment also demonstrated a manageable safety profile throughout the study, with the most common AEs being headache, nasopharyngitis, and COVID-19 infection. With these data, the MOBILIZE and VITALIZE phase 3 trials were initiated.^5,6

The phase 3 trials enrolled adults with CIDP who experienced failure or had an inadequate response to a standard of care treatment (MOBILIZE) and adults with CIDP receiving maintenance treatment with intravenous immunoglobulin (IVIg; VITALIZE). In MOBILIZE, patients receive either riliprubart or a placebo for 24 weeks, but both groups follow up initial treatment with riliprubart for a 24-week open-label extension phase. Primary end points consist of percentages of participants experiencing a response, those randomized to riliprubart with a lasting response, and those randomized to placebo who experience a response. Secondary end points include changes in baseline Inflammatory Raschbuilt Overall Disability Scale and adjusted inflammatory neuropathy cause and treatment disability scores, among others.^3,6

Similarly to MOBILIZE, patients enrolled in VITALIZE are randomly assigned to receive riliprubart with placebo IVIG or placebo for 24 weeks, followed by an open-label extension phase with riliprubart for 24 weeks. Both primary and secondary end points for this trial are also similar.^4,6

“[The] ODD for riliprubart marks an important milestone in our mission to address critical challenges in transplant medicine, leveraging our expertise in immunology. Antibody-mediated rejection represents a serious threat to transplanted organs and patient survival. Through riliprubart's innovative mechanism of action, we hope to bring forward a treatment option that could significantly improve outcomes for kidney transplant recipients,” Alyssa Johnsen, global therapeutic area development head, immunology and inflammation, Sanofi, said in a news release.¹

REFERENCES

1. Sanofi. Press Release: Riliprubart earns orphan drug designation in the US for antibody-mediated rejection in solid organ transplantation. News release. June 25, 2025. Accessed July 8, 2025. https://www.sanofi.com/en/media-room/press-releases/2025/2025-06-25-05-00-00-3104793

2. BIVV020 (SAR445088) in Prevention and Treatment of Antibody-mediated Rejection (AMR). ClinicalTrials.gov identifier: NCT05156710. Updated January 10, 2025. Accessed July 8, 2025. https://clinicaltrials.gov/study/NCT05156710

3. A Study to Test the Effects and Safety of Riliprubart in People With Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) for Which the Usual Treatments do Not Work (MOBILIZE). ClinicalTrials.gov identifier: NCT06290128. Updated June 17, 2025. https://clinicaltrials.gov/study/NCT06290128

4. A Study to Test the Efficacy and Safety of Riliprubart Against the Usual Treatment of Intravenous Immunoglobulin (IVIg) in People With Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) (VITALIZE). ClinicalTrialsl.gov identifier: NCT06290141. Updated July 1, 2025. Accessed July 8, 2025. https://clinicaltrials.gov/study/NCT06290141

5. Sanofi. Media Update: Riliprubart one-year results from phase 2 study underpin the potential as a first-in-class treatment in chronic inflammatory demyelinating polyneuropathy. News release. June 25, 2024. Accessed July 8, 2025. https://www.sanofi.com/en/media-room/press-releases/2024/2024-06-25-20-30-00-2904145

6. Lewis RA, Allen J, Merkies ISJ, et al. Two Phase 3 Trial Designs Evaluating Riliprubart, a C1s-Complement Inhibitor, in CIDP. Presented at: European Academy of Neurology (EAN) Congress. Helsinki, Finland. June 29–July 02, 2024. https://congress.sanofimedical.com/s3fs-public/2024-06/Phase%203%20Trial%20Designs%20Evaluating%20Riliprubart%2C%20a%20C1s-Complement%20Inhibitor%2C%20in%20CIDP.pdf?VersionId=w1h617SkZfB2CSg0HuzPUUCoZjdha9ds