By Ana Espino | Published on April 17, 2026 | 4min read
Hemophilia is a genetic bleeding disorder caused by a
deficiency in factor VIII (hemophilia A) or factor IX (hemophilia B), leading
to spontaneous or prolonged bleeding. It primarily affects males due to its
X-linked inheritance and represents a chronic condition that significantly
impacts quality of life.
Current treatments are mainly based on replacement therapy
with coagulation factors, administered either on demand or prophylactically.
Although effective, these treatments have several major limitations: high cost,
frequent intravenous injections that are burdensome for patients, and the
development of neutralizing antibodies (inhibitors) that can reduce their
effectiveness.
These limitations highlight current challenges: improving
adherence, reducing treatment burden, and providing effective options for
patients with inhibitors. In this context, this study was conducted to present
fitusiran, the first approved small interfering RNA (siRNA) therapy for
hemophilia, and to evaluate its mechanism of action, clinical efficacy, and
potential to transform disease management.
Can hemophilia be controlled differently ?
The study is based on the analysis of data from several
phase III clinical trials (ATLAS-INH, ATLAS A/B, and ATLAS-OLE), including
patients with hemophilia A or B, with or without inhibitors. These trials
compare prophylactic fitusiran with standard treatments (bypassing agents or
on-demand coagulation factor therapy).
Fitusiran works through an innovative mechanism: it targets
the SERPINC1 gene in the liver to reduce antithrombin production. This
reduction increases thrombin activity and restores coagulation balance,
independently of factor VIII or IX deficiency and regardless of the presence of
inhibitors.
Clinical trial results show a significant reduction in the
annualized bleeding rate (ABR) in patients treated with fitusiran:
• in patients with inhibitors: substantial reduction compared to bypassing
agents (5.1 vs 19.1),
• in patients without inhibitors: marked reduction compared to standard
treatments (9.0 vs 31.4).
Another major advantage is the simplicity of the dosing
regimen, with infrequent subcutaneous administration (every two months with
individualized adjustment), potentially improving treatment adherence.
However, adverse effects have been reported, including
thrombotic events, liver and biliary disorders, as well as infections. These
risks led to adjustments in the dosing regimen, based on monitoring
antithrombin activity to maintain a balance between efficacy and safety.
Rethinking coagulation
Hemophilia remains a chronic disease requiring long-term
management, with significant therapeutic constraints. The main challenges
involve reducing treatment burden, managing inhibitors, and improving patients’
quality of life.
This study aimed to present fitusiran as a novel and
innovative therapeutic approach based on RNA interference. The results show
that fitusiran represents a major advancement, offering a mechanism independent
of coagulation factors and a significant reduction in bleeding, while
simplifying treatment.
However, some limitations remain, particularly the risks of
thrombosis and liver toxicity, as well as the lack of long-term data on safety
and effectiveness in real-world settings.
Nevertheless, the outlook remains promising. Fitusiran could
sustainably transform hemophilia management and pave the way for other RNA
interference–based therapies, provided its long-term safety profile is
confirmed.
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About
the author –
Ana Espino
PhD in Immunology, specialized in Virology
As a scientific writer, Ana is passionate about bridging the gap
between research and real-world impact. With expertise in immunology, virology,
oncology, and clinical studies, she makes complex science clear and accessible.
Her mission: to accelerate knowledge sharing and empower evidence-based
decisions through impactful communication. 
