Can Six Shots a Year Keep Hemophilia Bleeding Away?

TOPLINE:

Fitusiran antithrombin-based dose regimen targeting 15%-35% of antithrombin activity demonstrated favorable safety profile in male participants aged ≥ 12 years with severe hemophilia A or B, with or without inhibitors. The median annualized bleeding rate was 3.7, with superior efficacy over on-demand treatments showing > 70% bleeding rate reduction.

METHODOLOGY:

• A multicenter, multinational, open-label, long-term extension study was initiated in January 2019 at 66 sites across 20 countries, enrolling participants from previous phase 3 studies (ATLAS-INH, ATLAS-A/B, and ATLAS-PPX).
• Participants included 213 males aged ≥ 12 years with severe hemophilia A or B, with or without inhibitors, who completed a previous fitusiran phase 3 study.
• Treatment involved an antithrombin-based dose regimen targeting antithrombin levels between 15% and 35%, starting at 50 mg once every 2 months, individually adjusted to 20, 50, or 80 mg monthly or 20 mg every 2 months based on monthly antithrombin measurements.
• Primary and secondary endpoints were safety and efficacy, respectively, with integrated safety analyses assessing antithrombin-based dose regimen and original dose regimen across all fitusiran studies.

TAKEAWAY:

• Among 227 enrolled participants, 213 received an antithrombin-based dose regimen, with 78% on every 2 months regimens.
• Safety analysis of 286 participants receiving an antithrombin-based dose regimen demonstrated treatment-emergent adverse events in 83.2% of participants, with serious events in 14.3%.
• The median annualized bleeding rate with antithrombin-based dose regimen was 3.7 (interquartile range, 0.0-7.5), with 31.5% of participants having zero treated bleeds.
• The mean antithrombin level was 23.5% (SD, 4.6) during the primary efficacy period, with 94% of participants requiring 0-1 dose adjustment to achieve target levels.

IN PRACTICE:

“This study confirms that fitusiran AT-DR [antithrombin-based dose regimen] was well tolerated and maintained clinically meaningful bleed protection in all PwHA/B [people with hemophilia A or B]. These outcomes confirm findings from previous fitusiran studies, suggesting that fitusiran provides an efficacious, SC [subcutaneous], prophylactic option for PwHA/B, irrespective of inhibitor status,” the authors of the study wrote.

SOURCE:

The study was led by Guy Young, Children’s Hospital Los Angeles, University of Southern California Keck School of Medicine in Los Angeles. It was published online in Blood.

LIMITATIONS:

According to the authors, the study was originally designed as a long-term extension study evaluating safety of fitusiran original dose regimen and later converted to a pivotal study evaluating safety and efficacy of antithrombin-based dose regimen. The open-label design may have resulted in potential biases, particularly in health-related quality-of-life outcomes. Most participants had been exposed to the higher fitusiran dose on the original dose regimen, although the safety profile of fitusiran-naive participants did not differ. The intention-to-treat analysis of fitusiran efficacy compared with clotting factor concentrate/bypassing agent on-demand and prophylaxis was limited by non-contemporaneous data collection and multiple imputations to account for missing data. Additionally, when initial phase 3 studies implementing the original dose regimen were conceived, such trials did not include women.

DISCLOSURES:

The study was funded by Sanofi. Young disclosed receiving grants from Sanofi; consulting fees from BioMarin, Centessa, CSL Behring, Genentech/Roche, Hema Biologics/LFB SA, Novo Nordisk, Octapharma AG, Pfizer, Sanofi, Spark Therapeutics, and Takeda; as well as speaking fees from BioMarin, CSL Behring, Genentech/Roche, Hema Biologics/LFB SA, Novo Nordisk, Octapharma, Pfizer, Rani, Sanofi, Spark Therapeutics, and Takeda. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.