At the 2025 annual American Society of Hematology (ASH) meeting, Sanofi presented a robust portfolio of data that solidifies its leadership in two distinct yet complementary arenas within rare blood diseases: the pioneering science of multi-immune modulation and the delivery of comprehensive hemophilia care.

The data reveal a company investing deeply in understanding disease mechanisms—from the complex immune dysregulation driving conditions like immune thrombocytopenia (ITP) to the pursuit of optimal factor replacement in hemophilia.

To understand the vision connecting these efforts, Drug and Device World spoke with Jeff Schaffnit, General Manager and Head of Rare Blood Diseases at Sanofi.

He provides insights into Sanofi’s strategic pillars, which are interwoven with a detailed examination of the key abstracts presented at ASH, painting a picture of a present and future where scientific innovation is relentlessly focused on holistic patient empowerment.

Connecting Two Strategic Pillars

Sanofi’s rare blood disease strategy is built on two foundational pillars: advancing Comprehensive Hemophilia Care through a portfolio of factor and non-factor therapies, and pioneering a new treatment paradigm via Multi-Immune Modulation, primarily through Bruton’s tyrosine kinase (BTK) inhibition.

For Schaffnit, these priorities are united by a single, overarching vision. “Our overarching vision, here at Sanofi, underscores our commitment to scientific innovation and understanding of how we can adapt and evolve current approaches in different disease areas to achieve more impactful outcomes for our patients.”

He elaborates that this approach is intentionally multi-pronged. In hemophilia, the goal is to provide a spectrum of options that offer robust, individualized protection. For other rare blood disorders, the focus shifts to targeting the root causes of immune dysregulation.

The data presented at ASH, Schaffnit notes, reflect this holistic ambition. “At ASH, our overall data highlight our determination to redefine care in rare blood disorders, addressing root causes of disease and supporting patient unmet needs holistically, looking at factors like health-related quality of life (HRQoL) and patient satisfaction.”

The following sections delve into the data that bring this dual vision to life, beginning with the expanding universe of BTK inhibition.

The recent US approval of Wayrilz (rilzabrutinib) for ITP marked a significant milestone for Sanofi’s immunoscience pipeline. At ASH 2025, the company showcased data exploring the potential of this BTK inhibitor beyond ITP, in warm autoimmune hemolytic anemia (wAIHA) and sickle cell disease (SCD), embodying the “multi-immune modulation” concept.

Targeting Immune Dysregulation

Schaffnit explains the fundamental science driving this focus. “BTK is a central regulator of both the innate and adaptive immune systems, playing a pivotal role in autoimmunity and inflammation… These conditions can create substantial clinical and quality-of-life burdens for patients, and for some patients, current treatments may fail to address the underlying immune dysregulation driving the disease. This represents a significant opportunity for BTK inhibition in ITP and beyond.”

This rationale is supported by data across multiple conditions, demonstrating a consistent approach to modulating the immune system at its core.

Deepening the ITP Story: Quality of Life and Steroid-Sparing Effects

New analyses from the Phase III LUNA3 study (NCT04562766) in ITP provided a nuanced view of Wayrilz’s impact. Beyond durable platelet responses, an abstract detailed meaningful improvement in self-reported women’s reproductive health, including reductions in heavy menstrual bleeding and improved perceptions around pregnancy and birth likelihood. Another presentation highlighted sustained improvements in fatigue and HRQoL during the open-label and long-term extension periods, with patients initially on placebo experiencing similar benefits after switching to Wayrilz.

Perhaps one of the most clinically significant findings came from the long-term extension study, which reported that among patients on concomitant corticosteroids (CS) at entry, 29% discontinued CS entirely and an additional 24% were able to substantially reduce their dose while maintaining platelet responses. This steroid-sparing potential addresses a major toxicity concern in chronic ITP management.

Expanding into Warm Autoimmune Hemolytic Anemia (wAIHA)

The Phase IIb LUMINA2 study (NCT05002777) in wAIHA offered compelling evidence for Wayrilz’s efficacy in another antibody-mediated disease. A post-hoc analysis focused on the debilitating symptom of fatigue, measured by the FACIT-Fatigue scale. The data showed clinically meaningful improvements in fatigue, which were most pronounced in patients who achieved a durable hemoglobin (Hb) response. Intriguingly, the analysis found only a weak-to-moderate correlation between fatigue improvement and Hb level increases, but a strong negative correlation with reductions in inflammatory markers like IL-10 and TNF-α/

Schaffnit adds, “Our recent approval of Wayrilz underscores our commitment to scientific innovation and to understanding how we can adapt and evolve current approaches in different disease areas to achieve even more impactful outcomes. Clinical studies exploring the potential of Wayrilz in rare conditions are ongoing in… warm antibody hemolytic anemia (wAIHA)… The innovation has been recognized with FDA Orphan Drug Designation for four conditions — ITP, IgG4-related disease, wAIHA, and SCD.”

Based on the Phase IIb results, Sanofi has initiated the Phase III LUMINA3 study (NCT07086976), a randomized, placebo-controlled trial designed to evaluate Wayrilz in patients with wAIHA who are relapsed/refractory or dependent on corticosteroids. The primary endpoint is the proportion achieving a durable Hb response.

BTK Inhibition in Sickle Cell Disease

The most novel application presented was in sickle cell disease (SCD). The scientific rationale posits that inflammation driven by innate immune cells (neutrophils, monocytes) is a key contributor to vaso-occlusive crisis (VOC) pathophysiology. Preclinical data in SCD mouse models showed Wayrilz reduced microvascular stasis and downregulated genes involved in inflammation and adhesion.

Schaffnit notes, “People with SCD often live with severe episodes of pain from vaso-occlusive crises and other complications that can significantly impact both quality of life and life expectancy. There is a need for novel treatment approaches to address these symptoms caused by immune dysregulation… SCD represents an important example of how immune dysregulation driven by BTK can lead to disease pathology.”

To test this hypothesis, Sanofi has designed the LIBRA Phase III trial (NCT06975865), which will randomize patients with SCD to Wayrilz or placebo to evaluate the annualized rate of clinical VOCs. This represents a bold exploration of immune modulation in a disease with significant unmet need.

Schaffnit notes, “The FDA’s Orphan Drug Designation for Wayrilz in SCD validates this novel approach, and our LIBRA Phase III trial is designed to evaluate whether BTK inhibition can meaningfully address the persistent unmet needs by tackling the disease from a different angle.”
Further emphasizing the disease-modifying ambition, Sanofi presented the design of the Phase IIIb LUNA4 study (NCT07007962). This trial will evaluate Wayrilz in patients with ITP after first-line corticosteroid failure, testing the hypothesis that earlier intervention with multi-immune modulation can improve outcomes and potentially lead to sustained response off treatment (SROT). This moves the treatment goalposts from chronic management toward potential remission.

Comprehensive Hemophilia Care

Parallel to its immunoscience advancements, Sanofi showcased the strength and depth of its hemophilia portfolio, anchored by long-term data for its high-sustained factor VIII therapy, ALTUVIIIO (efanesoctocog alfa), and real-world evidence for its non-factor therapy, Qfitlia (fitusiran).

ALTUVIIIO: Redefining Long-Term Prophylaxis

The third interim analysis of the XTEND-ed long-term extension study presented data with up to four years of follow-up in adults/adolescents and up to three years in children. The results demonstrated sustained, highly effective bleed protection. In adults/adolescents, the mean model-based annualized bleeding rate (ABR) for overall treated bleeds was 0.60, with 78% of participants experiencing zero bleeds in the Months 24-36 analysis period. No FVIII inhibitors developed.

Schaffnit adds, “The new four-year ALTUVIIIO data represents a shift in hemophilia care. While sustained bleed protection is crucial, what’s maybe even more meaningful is how this long-term efficacy combined with once weekly dosing fundamentally changes patients’ relationship with their disease.”

He also connects clinical data to lived experience. “When patients achieve high sustained factor levels over years with simplified treatment schedules, they gain something beyond just clinical efficacy — they gain the freedom to focus more on life outside of their disease management. This shifts our definition of comprehensive care from just preventing bleeds to truly enabling patients to live life on their own terms. That’s the real measure of treatment success.”

This theme of life impact was echoed in real-world studies. A retrospective US chart review of 41 patients who switched to ALTUVIIIO from other therapies showed meaningful reductions in ABRs. Notably, 13 patients switched from emicizumab, reporting improved protection during physical activity and better joint bleed control as key reasons. A separate patient survey found that after switching to ALTUVIIIO, 83.9% of patients rated it better than prior therapies for hemophilia control, with significant improvements reported in difficulty with walking and avoidance of physical activity.

Qfitlia: High Compliance with an AT-Based Dosing Regimen

For its non-factor therapy Qfitlia, Sanofi emphasized treatment experience and management. An analysis from the ATLAS-OLE study, which uses an antithrombin-based dose regimen (AT-DR) targeting 15-35% AT activity, reported high treatment compliance. The overall mean compliance was 96.0%, with 78% of participants on a once-every-two-months (Q2M) regimen. Discontinuation due to adverse events was low (2.3%).

Schaffnit adds, “At ASH, we are taking that story further by showing high treatment compliance with Qfitlia. We believe this is directly connected to the reduced treatment frequency of as few as six subQ doses per year, making a real difference in how patients live their lives.”

Additional data reinforced Qfitlia’s utility in clinical practice. An analysis of 71 minor surgeries performed across the Qfitlia clinical program showed excellent/good hemostatic control on the day of surgery in 95% of assessed cases, without the need for ATIII concentrate reversal in 99% of procedures. Furthermore, the design of the Phase IV SWITCH study (NCT06145373), an ongoing trial investigating the transition from emicizumab to Qfitlia prophylaxis, was presented, addressing a growing practical question in hemophilia management.

The Patient Perspective

A qualitative interview study provided a poignant counterpoint to clinical metrics, directly capturing the voices of 69 adults with severe hemophilia A. Despite treatment with extended half-life factors or emicizumab, patients reported a substantial ongoing burden, including breakthrough bleeds, pain, and the need for additional factor infusions. Over 90% reported daily disability adaptations, and a majority expressed a desire for a higher level of protection and longer treatment coverage. This study underscores why the pursuit of “comprehensive care” remains critical, driving innovation toward therapies that further reduce this residual burden.

A Future Built on Mechanistic Insight

The breadth of data presented by Sanofi at ASH 2025 reveals a company executing a clear, two-pronged strategy with scientific rigor. In hemophilia, the focus is on optimizing protection and convenience across factor and non-factor mechanisms, as demonstrated by the long-term efficacy of ALTUVIIIO and the high compliance with Qfitlia’s AT-based regimen.

In the realm of immune-mediated rare blood disorders, the strategy is more transformative, seeking to establish a new paradigm. Through the BTK inhibitor Wayrilz, Sanofi is targeting a common node of immune dysregulation across diverse diseases—ITP and investigationally in wAIHA and SCD. The data consistently show not only improvements in primary hematologic parameters but also in critical patient-centric outcomes: reducing fatigue, improving quality of life, enabling steroid tapering, and addressing specific burdens like heavy menstrual bleeding in ITP.

Schaffnit notes, “What excites me most looking across the rare blood disorder landscape is our expansion into immune-mediated conditions, particularly through our Wayrilz BTK inhibitor program. Our findings validate our scientific hypothesis about targeting the fundamental immune dysregulation driving diseases like ITP, rather than just managing symptoms.”

He sees this as a template for future innovation. “It’s a perfect example of how deep mechanistic understanding can open new frontiers in treating rare blood disorders, potentially transforming care for multiple patient communities through a single scientific platform.”