Rare Blood Disease Innovations Address Unmet Needs, According to ASH Data

Innovations in rare blood disorders took center stage at ASH 2024.

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Innovations in rare blood disorders took center stage at the 2024 American Society of Hematology (ASH) Annual Meeting & Exposition, with Sanofi highlighting 49 abstracts, including 9 oral presentations, featured at the conference in San Diego.¹ Key research was presented on immune thrombocytopenia (ITP), hemophilia, and multiple myeloma (MM), among other disease states.

With new findings related to approved and investigational therapies alike, the diverse portfolio demonstrates the extent of unmet needs across rare blood disorders while making strides in addressing them.

Transformative Data Across Rare Blood Diseases

Immune Thrombocytopenia: LUNA 3 Phase 3 Study Results

Investigators unveiled positive efficacy, safety, and quality of life outcomes from the LUNA 3 phase 3 study, which evaluated rilzabrutinib (PRN1008) for ITP. As a first-in-class oral, reversible, covalent Bruton tyrosine kinase (BTK) inhibitor, rilzabrutinib represents a potential breakthrough in treating ITP. While still under clinical investigation, the study’s findings highlighted its promise for future care paradigms.

The first set of LUNA 3 data were derived from 202 randomized patients; 65% of those treated with rilzabrutinib achieved a platelet response compared with 33% in the placebo group, with 23% meeting the primary end point of a durable platelet response.² In contrast, no placebo patients achieved this milestone (P < .0001). Rilzabrutinib also reduced the need for rescue therapy by 52%, improved physical fatigue and bleeding scores, and achieved a median time to initial platelet response of 15 days in responders. Adverse events were predominantly mild to moderate, with comparable rates of serious adverse events across both groups.

The second set of LUNA 3 data showed that improvements extended across multiple health-related quality-of-life (HRQoL) domains, including psychological health, overall HRQoL, symptoms, and social activity.³ Rilzabrutinib also enhanced health status (EQ-VAS), further highlighting its benefits beyond platelet count normalization. These findings suggest that rilzabrutinib may address both clinical and quality-of-life aspects of ITP.

Advancing Hemophilia Care

New data were presented from the ATLAS-OLE phase 3 study of fitusiran, an investigational antithrombin-lowering therapy for patients with hemophilia A or B, including those with inhibitors.¹ Fitusiran’s pivotal data, which demonstrated significant bleed protection, was complemented by findings on its management potential. The therapy is under regulatory review in the US and China, with a target FDA action date of March 28, 2025.

Additionally, data from ALTUVIIIO’s XTEND-1 phase 3 study emphasized its impact on joint health and quality of life in patients with severe hemophilia A. Interim outcomes from the XTEND-ed phase 3 extension study further bolstered its long-term efficacy profile.

Groundbreaking Advances in Multiple Myeloma

Front-Line Therapy: Sarclisa in Combination Regimens

ASH data highlighted the role of isatuximab (Sarclisa) in front-line therapy for multiple myeloma (MM). A key aspect of the data was exhibited in the IMROZ phase 3 study, exploring minimal residual disease (MRD) negativity in patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM) and treated with isatuximab in combination with bortezomib, lenalidomide, and dexamethasone (VRd).

Part 1 of the German-speaking Myeloma Multicenter Group (GMMG)-HD7 phase 3 study evaluating isatuximab with lenalidomide, bortezomib, and dexamethasone (RVd) in patients who were transplant-eligible NDMM was featured in a pair of oral presentations. These results reinforce isatuximab’s potential to improve outcomes across multiple patient populations.

Expanding Research Horizons

Interim results from the ISAMYP phase 2 study showcased isatuximab’s potential in relapsed AL amyloidosis when combined with pomalidomide and dexamethasone (Pd). While investigational, these data pave the way for broader applications of isatuximab beyond MM, Sanofi stated. Additionally, ongoing research into NK Cell Engagers (NKCE) underscored the company’s focus on novel therapeutic strategies.

A Vision for Transforming Care

“The breadth of data featured at ASH reflects our decades-long commitment to advancing first and best-in-class medicines in rare blood diseases,” Dietmar Berger, MD, PhD, chief medical officer and global head of Development at Sanofi, said in the statement. “From new phase 3 data for rilzabrutinib to continued progress for Sarclisa in multiple myeloma, our work demonstrates a relentless pursuit of evolving care for people living with these challenging conditions.”

References

1. ASH: new data underscore Sanofi's commitment to innovation in rare blood diseases and cancers. News release. Sanofi. December 3, 2024. https://www.news.sanofi.us/2024-12-03-ASH-New-data-underscore-Sanofis-commitment-to-innovation-in-rare-blood-diseases-and-cancers

2. Kuter DJ, Ghanima W, Cooper N, et al. Efficacy and safety of oral Bruton Tyrosine Kinase inhibitor (BTKi) rilzabrutinib in adults with previously treated immune thrombocytopenia (ITP): a phase 3, placebo-controlled, parallel-group, multicenter study (LUNA 3). Presented at: 66th ASH Annual Meeting & Exposition; December 7-10, 2024; San Diego, CA. Abstract 5.

3. Ghanima W, Liebman HA, Hu Y, et al. Improved health-related quality of life (HRQoL) with oral Bruton Tyrosine Kinase inhibitor (BTKi) rilzabrutinib vs placebo in adults with previously treated immune thrombocytopenia (ITP): phase 3 LUNA 3 multicenter study. Presented at: 66th ASH Annual Meeting & Exposition; December 7-10, 2024; San Diego, CA. Abstract 2552.