riliprubart (SAR445088) / Sanofi - LARVOL DELTA

VITALIZE: 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) (clinicaltrials.gov) - P3 | N=160 | Recruiting | Sponsor: Sanofi | Trial completion date: May 2027 ➔ Nov 2027

Trial completion date • Pain

Beneath the surface in autoimmune hemolytic anemia: pathogenetic networks, therapeutic advancements and open questions. (PubMed, Front Immunol) - "Glucocorticoids remain the standard first-line therapy for warm AIHA; in contrast, CAD/CAS is increasingly managed with agents targeting B-cell function or complement activation, including rituximab and sutimlimab...Emerging therapeutics targeting the classical complement pathway include novel anti-C1s monoclonal antibodies such as riliprubart, which exhibits an extended half-life due to enhanced affinity for the neonatal Fc receptor. Parallel strategies aim to disrupt B-cell receptor (BCR) signaling cascades, employing Bruton tyrosine kinase (BTK) inhibitors such as ibrutinib, spleen tyrosine kinase (SYK) inhibitors such as fostamatinib and sovleplenib, and phosphoinositide 3-kinase (PI3K) inhibitors such as parsaclisib. Collectively, these advances are reshaping the therapeutic landscape of AIHA toward a precision medicine model guided by mechanistic insights into disease biology. In this review, we delineate the evolving immunopathogenesis of AIHAs and examine..."

Journal • Review • Anemia • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Immunology • SYK

Press Release: Riliprubart granted orphan drug designation in Japan for chronic inflammatory demyelinating polyneuropathy (GlobeNewswire) - "The Ministry of Health, Labour and Welfare (MHLW) in Japan has granted orphan drug designation to riliprubart, a monoclonal antibody that selectively inhibits activated C1s in the classical complement pathway for people with chronic inflammatory demyelinating polyneuropathy (CIDP)...Long-term, 76-week sustained efficacy and safety data from riliprubart’s phase 2 study were presented at the Peripheral Nerve Society meeting in Edinburgh, UK on May 17-20, 2025. Findings suggest a potential sustained long-term benefit provided by riliprubart across a broad spectrum of participants with CIDP."

Orphan drug • Immunology • Inflammation

Press Release: Riliprubart earns orphan drug designation in the US for antibody-mediated rejection in solid organ transplantation (GlobeNewswire) - "The US Food and Drug Administration (FDA) has granted orphan drug designation to riliprubart for the investigational treatment of antibody-mediated rejection (AMR) in solid organ transplantation. This designation reflects Sanofi’s commitment to addressing a critical unmet need in transplant medicine, where AMR remains a significant challenge with no FDA-approved treatments available."

Orphan drug • Antibody-mediated Rejection • Solid Organ Transplantation

Antibody-mediated Rejection - Treatment Standard. (PubMed, Nephrol Dial Transplant) - "We conclude that steroids, rituximab, bortezomib, and interleukin-6 (IL-6) antagonists lack sufficiently robust evidence to support their use in AMR. Along these lines, in severe early AMR, complement inhibition may also be an option. Ongoing phase 2 trials evaluating prolonged courses of high dose IVIG, the neonatal Fc receptor blocker efgartigimod, the tyrosine kinase inhibitor fostamatinib, and the complement inhibitor BIVV020, along with phase 3 trials of the anti-IL-6 receptor antibody tocilizumab and the CD38 antibody felzartamab, offer hope for effective, approved therapies targeting different aspects of AMR pathobiology."

Journal • Antibody-mediated Rejection • Inflammation • Transplantation

Biomarker and Subgroup Insights on Novel CIDP Therapy Riliprubart: Luis Querol, MD, PhD (NeurologyLive) - P2 | N=110 | NCT04658472 | Sponsor: Bioverativ, a Sanofi company | "New biomarker and exploratory data from a phase 2 study (NCT04658472) assessing riliprubart in CIDP were presented at the recent Peripheral Nerve Society (PNS) Annual Meeting, held May 17-20, in Edinburgh, Scotland. Overall, the analyses revealed that treatment with the agent resulted in reduced neurofilament light levels, a biomarker of neuroaxonal damage, in patients with CIDP. More notably, greater reductions in NfL levels were associated with higher treatment response rates, as measured by Inflammatory Neuropathy Cause and Treatment (INCAT) Disability score."

P2 data • CNS Disorders

LTS: Long-term Safety and Efficacy Study of Riliprubart in Participants With CIDP (clinicaltrials.gov) - P3 | N=300 | Recruiting | Sponsor: Sanofi | Not yet recruiting ➔ Recruiting

Enrollment open • Pain

Confirmation of Fixed Quarterly Riliprubart Regimen in Patients with Cold Agglutinin Disease Using Population PK/PD and Exposure-Response Analyses. (PubMed, Clin Pharmacol Ther) - "The observed riliprubart concentration-time profiles from 9 CAD patients were consistently within the popPK simulated 90% prediction interval. Based on the totality of the efficacy, safety, and PK/PD data observed under clinical evaluation, the proposed dose regimen demonstrated suitability for CAD patients."

Journal • PK/PD data • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Immunology

Phase 2 Efficacy and Safety of Riliprubart, a C1s-Complement Inhibitor, in Chronic Inflammatory Demyelinating Polyneuropathy (S16.009). (PubMed, Neurology) - P2 | "Dr. Hughes has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi."

Journal • P2 data • Fatigue • Infectious Disease • Pain • NEFL • Plasma NfL

Safety and Tolerability Study in Adults With Cold Agglutinin Disease Previously Treated With SAR445088 or Never Treated With SAR445088 (clinicaltrials.gov) - P1 | N=9 | Terminated | Sponsor: Bioverativ, a Sanofi company | Trial completion date: Jan 2026 ➔ Mar 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jan 2026 ➔ Mar 2025; Business decision, not related to any safety or efficacy issues.

Trial completion date • Trial primary completion date • Trial termination • Anemia • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Immunology

Phase 3 Trial Designs Evaluating Riliprubart, a C1s-Complement Inhibitor, in Chronic Inflammatory Demyelinating Polyneuropathy (AAN 2025) - P2, P3 | "These Phase 3 trials aim to demonstrate efficacy and safety of riliprubart in people with CIDP, including participants with residual disability or refractory disease despite SOC therapies."

P3 data • Pain • NEFL

Phase 2 Efficacy and Safety of Riliprubart, a C1s-Complement Inhibitor, in Chronic Inflammatory Demyelinating Polyneuropathy (AAN 2025) - P2 | "These preliminary results support riliprubart's proof-of-concept in CIDP, with a favorable benefit:risk profile, supporting further investigation as a potential new therapy for people with CIDP who experienced failure/inadequate response to SOC treatments and those with residual disability despite maintenance treatment."

Clinical • P2 data • Fatigue • Infectious Disease • Pain • NEFL • Plasma NfL

LTS: Long-term Safety and Efficacy Study of Riliprubart in Participants With CIDP (clinicaltrials.gov) - P3 | N=300 | Not yet recruiting | Sponsor: Sanofi

New P3 trial • Pain

BIVV020 (SAR445088) n Prevention and Treatment of Antibody-mediated Rejection (AMR) (clinicaltrials.gov) - P2 | N=48 | Active, not recruiting | Sponsor: Sanofi | Recruiting ➔ Active, not recruiting

Enrollment closed • Antibody-mediated Rejection • Immunology • Transplant Rejection • Transplantation

BIVV020 (SAR445088) n Prevention and Treatment of Antibody-mediated Rejection (AMR) (clinicaltrials.gov) - P2 | N=45 | Recruiting | Sponsor: Sanofi | Trial primary completion date: Nov 2024 ➔ Dec 2025

Trial primary completion date • Antibody-mediated Rejection • Immunology • Transplant Rejection • Transplantation

Autoimmune Hemolytic Anemias: Challenges in Diagnosis and Therapy. (PubMed, Transfus Med Hemother) - "Therapy is quite different, as steroids and rituximab are effective in the former, but have a lower response rate and duration in the latter...Several new drugs are increasingly used or are in trials for relapsed/refractory AIHAs, including B-cell (parsaclisib, ibrutinib, rilzabrutinib), and plasma cell target therapies (bortezomib, daratumumab), bispecific agents (ianalumab, obexelimab, povetacicept), neonatal Fc receptor blockers (nipocalimab), and complement inhibitors (sutimlimab, riliprubart, pegcetacoplan, iptacopan)...Along with all these variables, there are rare forms like mixed (wAIHA plus CAD), atypical (IgA or warm IgM driven), and DAT negative, where the diagnosis and clinical management are particularly challenging. This article covers the classic clinical features, diagnosis, and therapy of wAIHA and CAD, and focuses, with the support of clinical vignettes, on difficult diagnosis and refractory/relapsing cases requiring novel therapies."

Journal • Review • Anemia • Autoimmune Hemolytic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Immunology • Infectious Disease • Oncology • Rare Diseases • Thrombosis • Transplantation

Psychometric Validation of the Inflammatory-Rasch-Built Overall Disability Scale (I-RODS) and Modified Rasch-Built-Fatigue Severity Scale (R-FSS) in Adult Patients With Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) (ISPOR-EU 2024) - P2 | "OBJECTIVES: Psychometrically validate and derive meaningful change thresholds for the Inflammatory-Rasch-built Overall Disability Scale (I-RODS) and Modified Rasch-built-Fatigue Severity Scale (R-FSS) using clinical trial data on Riliprubart in Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) patients... I-RODS and R-FSS are acceptable as endpoint measures in clinical trials in adult CIDP patients."

Clinical • CNS Disorders • Depression • Fatigue • Mood Disorders • Pain • Psychiatry

Use of Riliprubart (SAR445088) in cold agglutinin disease (CAD): Interim analysis confirms acceptable efficacy and safety with 12-week intravenous administration in Part 2 of the long-term Phase 1b study (DGHO 2024) - P1 | "These results support 12-weekly IV administration of 3.5 g of riliprubart, with an additional dose on Day 29 after the initial dose, for the Phase 3 study."

Clinical • P1 data • Anemia • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Lymphoma • Lymphoplasmacytic Lymphoma • Meningococcal Infections • Systemic Lupus Erythematosus • Waldenstrom Macroglobulinemia

Pharmacokinetics, pharmacodynamics, safety, and tolerability of a single-dose riliprubart, an anti-C1s humanized monoclonal antibody in East-Asian Adults: results from a phase 1, randomized, open-label trial. (PubMed, Expert Opin Investig Drugs) - "These results are comparable tofirst-in-human study results from non-East-Asian participants and support thesame dosing regimen of riliprubart for global simultaneous clinicaldevelopment. https://cris.nih.go.kr(identifier: KCT0006571)."

Journal • P1 data • PK/PD data

Phase 2 Efficacy and Safety of Riliprubart, a C1s-Complement Inhibitor, in CIDP (EAN 2024) - P2 | "These preliminary results support proof- of- concept for riliprubart in CIDP, with a favourable benefit- risk profile, supporting further investigation in Phase- 3."

Clinical • P2 data • Pain

Two Phase 3 Trial Designs Evaluating Riliprubart, a C1s-Complement Inhibitor, in CIDP (EAN 2024) - P2 | "These Phase 3 trials aim to demonstrate riliprubart efficacy for CIDP, including people with refractory disease or residual disability."

P3 data • Pain

RILIPRUBART (SAR445088) IN COLD AGGLUTININ DISEASE: INTERIM ANALYSIS FROM PART 2 OF A LONG-TERM PHASE 1B TRIAL CONFIRMS ACCEPTABLE EFFICACY AND SAFETY WITH 12-WEEKLY IV ADMINISTRATION (EHA 2024) - P1 | "These safety, efficacy, PK, and PD results support IV administration of 3. 5 g of riliprubart every 12 weeks, withan additional IV infusion on Day 29 after the initial dose, for the Phase 3 study."

Clinical • P1 data • Anemia • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Lymphoma • Lymphoplasmacytic Lymphoma • Meningococcal Infections • Systemic Lupus Erythematosus • Waldenstrom Macroglobulinemia

VITALIZE: 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) (clinicaltrials.gov) - P3 | N=160 | Recruiting | Sponsor: Sanofi | Not yet recruiting ➔ Recruiting

Enrollment open • Pain

Preliminary Efficacy and Safety Data from the Phase 2 Trial of Riliprubart (SAR445088), a Humanized Monoclonal Antibody Targeting Complement C1s, in Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) (AAN 2024) - P2 | "These proof-of-concept results demonstrate a favorable benefit:risk profile of riliprubart, which will be further investigated in Phase 3."

Clinical • P2 data • Fatigue • Infectious Disease • Pain • C1S • NEFL • Plasma NfL

MOBILIZE: 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 (clinicaltrials.gov) - P3 | N=140 | Recruiting | Sponsor: Sanofi | Not yet recruiting ➔ Recruiting

Enrollment open • Pain