EVOLVING THE TREATMENT LANDSCAPE WITH THE FIRST THERAPY APPROVED FOR PEOPLE WITH HEMOPHILIA A AND B WITH OR WITHOUT INHIBITORS

Content sponsored and created by Sanofi

Scientific advances in hemophilia have improved patient outcomes, but unmet needs remain for the over one million people worldwide who live with the disease.^1-3 Ongoing innovation is significantly evolving hemophilia care, including the introduction of a novel treatment aimed at rebalancing blood hemostasis instead of replacing missing factors.^3,4 This first-in-class approach is based on lowering antithrombin (AT), and it seeks to minimize the challenges associated with frequent infusions, including those caused by the presence of factor inhibitors, and aims to make hemophilia care more manageable for patients and caregivers.^3-6

A novel approach to hemophilia treatment: Help restore hemostasis by lowering AT

For people with hemophilia, deficiencies in factor VIII (hemophilia A) or factor IX (hemophilia B) lead to insufficient thrombin generation, which can lead to excessive or spontaneous bleeding.^3,7

In March 2025, the US Food and Drug Administration (FDA) approved Qfitlia™ (fitusiran), the first AT-lowering therapy, for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients aged 12 or older with hemophilia A or B with or without factor VIII or IX inhibitors.⁴

Qfitlia works differently than other prophylactic treatments because it is a double-stranded small interfering ribonucleic acid (siRNA) therapy designed to lower AT, an inhibitor of thrombin.^4,8,9 By binding to and degrading the AT messenger ribonucleic acid (mRNA), Qfitlia reduces the production of AT in the liver, which helps restore hemostasis and, as a result, a stable clot forms.^4,8,9

Its innovative siRNA technology enables low treatment frequency, subcutaneous
dosing, and low-volume injections. Qfitlia offers the fewest doses of any
prophylactic therapy.⁴

Proven bleed protection with as few as six injections per year^a

Qfitlia’s approval was supported by positive data from the ATLAS clinical development program.⁴ Qfitlia’s efficacy and safety were evaluated in adult and pediatric patients aged 12 and older with severe hemophilia A or B with or without inhibitors. The ATLAS clinical program included two parent studies (ATLAS-INH^b and ATLAS-A/B^c), a supportive study (ATLAS-PPX^d), and an open-label extension study (ATLAS-OLE^e). In the open-label extension study, patients received Qfitlia under an antithrombin-based dosing regimen (AT-DR), which aimed to maintain AT levels between 15%-35% to help mitigate the risk of thrombotic events (TEs).^4,f The efficacy of Qfitlia AT-DR treatment was assessed by comparing the AT-DR treatment data from the long-term extension study, ATLAS-OLE, to the control data from studies ATLAS-INH and ATLAS-A/B.⁴

Treatment with Qfitlia under the AT-DR resulted in significant bleed reduction when compared with on-demand therapies, including a 71% reduction in estimated annualized bleeding rate (ABR) compared with on-demand treatment with clotting factor concentrates in patients without inhibitors (CFCs; mean ABR: 9.0 vs 31.4, respectively, P<.0001). It also showed a 73% reduction in estimated ABR when compared with on-demand treatment with bypassing agents in patients with inhibitors (BPAs; mean ABR: 5.1 vs 19.1, respectively, P=.0006; Figure 1).^4,g

Figure 1

ABRs of Qfitlia following prior BPA or CFC prophylaxis were reduced or comparable, respectively (estimated mean ABR for BPA: 3.41 vs 11.29; estimated mean ABR for CFC: 6.93 vs 5.96).¹⁰ These data are exploratory in nature and are not statistically proven. Results are descriptive, and definitive conclusions cannot be made.

In ATLAS-OLE, the median observed ABR was 3.8 (interquartile range [IQR]: 0.0-11.2) in patients without inhibitors and 1.9 (IQR: 0.0-5.6) in patients with inhibitors.^4,g Median observed annualized spontaneous bleeding rate (AsBR) was 1.9 (IQR: 0.0-7.5) in patients without inhibitors and 1.9 (IQR: 0.0-3.7) in patients with inhibitors.^g Nearly half of patients experienced one or fewer bleeds (31% experienced 0 bleeds and 47% experienced 0-1 bleeds; Figure 2).¹⁰ These data are exploratory in nature and are not statistically proven. Results are descriptive, and definitive conclusions cannot be made.

Figure 2

The safety of Qfitlia has been extensively studied in the largest hemophilia preapproval clinical program to date.¹⁰ Potential significant adverse reactions with Qfitlia include TEs, acute and recurrent gallbladder disease, and hepatotoxicity. TEs were reported in 2.6% of patients receiving the 80 mg once monthly dose of Qfitlia (2.3 events per 100 person-years), including a fatal event of cerebral venous sinus thrombosis. The 80 mg once monthly dose is not approved or recommended for use. TEs were reported in 1.4% of patients receiving Qfitlia prophylaxis under the AT-DR (0.8 events per 100 person-years).⁴ In 270 patients who received the 80 mg once monthly dose of Qfitlia, which is not approved or recommended, 17% experienced gallbladder events and 4% underwent cholecystectomy. In 286 patients who received Qfitlia prophylaxis under the AT-DR, 3.8% experienced gallbladder events and 0.3% underwent cholecystectomy.⁴ On the AT-DR, 3.4% of patients treated with Qfitlia had at least one alanine aminotransferase (ALT) value greater than 3 times the upper limit of normal, with a median onset of 89 days after initial dosing (range: 15 to 768 days).⁴ Dosage interruptions due to increased transaminases occurred in 2 out of 286 (0.7%) patients.⁴ Obtain baseline liver function tests, including aspartate aminotransferases, ALT, and total bilirubin, prior to initiating Qfitlia: monthly for at least the first 6 months of Qfitlia use; monthly for at least 6 months after a dose increase; and periodically thereafter as clinically indicated.⁴

The most common adverse reactions (incidence >10%) are viral infection, nasopharyngitis, and bacterial infection.⁴ Prescribers should follow the Bleed Management Guidelines (BMGs) outlined in Qfitlia’s label and monitor patients for thrombosis risk. Risk may be higher in people with persistent AT levels <15% or existing comorbidities, when BMGs are not followed in the post-operative state, when indwelling venous catheters are present, and Qfitlia is utilized at the not-approved fixed dose of 80 mg monthly (non-AT-DR dosing). Safety and dosing decisions are at the discretion of prescribers and their patients.

^aIn the clinical study of 227 people, ~67% of people with hemophilia took Qfitlia every other month, and 19% took it monthly.⁴

^bATLAS-INH was a randomized, multicenter, open-label clinical study in 57 adult and pediatric males (aged ≥12 years) with hemophilia A or B with inhibitory antibodies to factor VIII or factor IX who had previously received on-demand (episodic) treatment with BPAs for bleeding.⁴

^cATLAS-A/B was a randomized, multicenter, open-label clinical study in 120 adult and pediatric males (aged ≥12 years) with hemophilia A or B without inhibitory antibodies to factor VIII or factor IX who had previously received on-demand (episodic) treatment with factor replacement for bleeding. Eligible patients in both trials were randomly assigned in a 2:1 ratio to receive Qfitlia prophylaxis (80 mg subcutaneously once monthly) or the comparator arm (BPA on-demand or factor replacement on-demand, respectively) to treat breakthrough bleeding episodes for 9 months.⁴

^dATLAS-PPX was an exploratory, phase 3, open-label study evaluating the efficacy and safety of Qfitlia prophylaxis in 80 males aged ≥12 years with hemophilia A or B, with or without inhibitors, who had received prior BPA or factor replacement prophylaxis. Participants continued their prior BPA or factor replacement prophylaxis for 6 months before switching to once-monthly 80 mg Qfitlia prophylaxis for 7 months (onset and efficacy periods).¹¹

^eATLAS-OLE, a multicenter, multinational, open-label extension study, assessed the safety and efficacy of Qfitlia using dose modifications based on antithrombin activity levels.⁴

^fTo mitigate the risk of thrombotic events, an AT-DR with the target antithrombin activity range of 15% to 35% was implemented in ATLAS-OLE when studies ATLAS-INH and ATLAS-A/B were nearly completed.^4,12

^gBased on treated bleeds.⁴

^hThe integrated efficacy analyses were conducted according to the intention-to-treat principle, preserving the randomization from the parent studies. The efficacy of Qfitlia was evaluated in 177 patients, comparing Qfitlia prophylaxis under the AT-DR in ATLAS-OLE and BPA or factor replacement on-demand in the parent studies.⁴

Dosing to fit your patients' profile

Qfitlia dosing is guided by AT levels, which can be easily and reliably measured in plasma to personalize treatment. Under the AT-DR study (n=227), approximately 67% of people with hemophilia took Qfitlia every other month and 19% took it monthly (Figure 3).⁴

Figure 3

While taking Qfitlia, AT levels should be maintained between 15%-35%.⁴ AT levels must be measured, and the dose of Qfitliaⁱ, can be adjusted, if needed. In the US, AT levels must be measured using a FDA-cleared companion diagnostic (CDx). Currently, the only one available is the INNOVANCE^® Antithrombin assay from Siemens Healthineers. The INNOVANCE Antithrombin assay has been tested in multiple studies, which successfully demonstrated the assay’s precision in measuring AT levels at clinical decision points of 15%-35% and is most suitable for clinical management of patients taking Qfitlia.

Sanofi has partnered with Labcorp on the Qfitlia (fitusiran) Testing Program to make the FDA-cleared CDx available for AT measurement to patients receiving Qfitlia at no cost. One AT test is required before the starting dose of Qfitliaⁱ, and tests are required at months 1, 3, 5, and 6 after starting treatment and after any dose adjustments.⁴ If no dose adjustment is needed, then individuals can maintain their dosing regimen with annual AT testing.⁴ In one clinical trial, 35% of patients required no dose adjustments from the recommended starting dose and 55% required one dose adjustment to achieve antithrombin levels between 15%-35%.¹²

By offering consistent protection with as few as six injections per year, Qfitlia provides a solution to fit your patients’ needs. As a first-of-its-kind therapy, Qfitlia reinforces Sanofi’s commitment to reimagining treatment paradigms for the rare blood disorders community.⁴

To learn more about Qfitlia, please visit https://pro.campus.sanofi/us/products/qfitlia.

ⁱDo not initiate Qfitlia dosing if AT activity is <60% at baseline.⁴

^jAdditional measurements can be considered if bleeding control is not adequate.⁴

Indication and Important Safety Information

INDICATION

Qfitlia™ (fitusiran) is an antithrombin (AT)-directed small interfering ribonucleic acid (siRNA) indicated for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients aged 12 years and older with hemophilia A or B with or without Factor VIII or IX inhibitors.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Thrombotic Events:

• Serious thrombotic events have been reported in Qfitlia-treated patients. Thrombotic events were reported in 2.6% of patients receiving the 80 mg once monthly dose, including a fatal event of cerebral venous sinus thrombosis. The 80 mg once monthly dose is not approved or recommended for use. Thrombotic events were reported in 1.4% of patients receiving Qfitlia prophylaxis using the AT-based dose regimen (AT-DR) that targeted AT activity 15-35%.
• The risk of thrombosis is greater in patients with certain risk factors (see Boxed WARNING). Treatment of breakthrough bleeding episodes with clotting factor concentrate (CFC) or bypassing agent (BPA) at a dose greater or more frequent than recommended may also increase thrombotic risk.

Acute and Recurrent Gallbladder Disease:

• Treatment with Qfitlia is associated with an increased occurrence of acute and recurrent gallbladder disease, including cholelithiasis and cholecystitis (see Boxed WARNING). In the 270 patients in the clinical studies who received Qfitlia at a fixed dose of 80 mg once monthly, 17% experienced gallbladder events and 4% underwent cholecystectomy. In 286 patients who received the AT-DR, 3.8% experienced gallbladder events and 0.3% underwent cholecystectomy.

Hepatotoxicity:

• In the two randomized studies testing Qfitlia 80 mg once monthly, alanine transaminase (ALT) and aspartate transaminase (AST) elevations above 3 times the upper limit of normal (ULN) occurred in 32% of patients with hemophilia with inhibitors and 18% of patients with hemophilia without inhibitors. There was one case of moderate hepatic injury attributable to Qfitlia use. On the AT-DR, 3.4% of patients treated with Qfitlia had at least one ALT value >3x ULN.
• Avoid use of Qfitlia in patients with hepatic impairment (Child-Pugh Class A, B, and C).
• Obtain baseline liver tests, including AST, ALT, and total bilirubin, prior to initiating Qfitlia, monthly for at least the first 6 months of Qfitlia use, monthly for at least 6 months after a dose increase, and periodically thereafter as clinically indicated.
• If new or worsening liver test abnormalities occur, initiate medical management as appropriate and monitor until they return to baseline. If ALT or AST elevations >5x ULN occur, interrupt Qfitlia treatment. If Qfitlia is restarted and ALT or AST elevations >5x ULN reoccur or the patient experiences jaundice due to hepatotoxicity with other causes of liver test elevation ruled out, permanently discontinue Qfitlia.

DRUG INTERACTIONS

Hypercoagulability with Concomitant Use of CFC or BPA: Qfitlia prophylaxis leads to increased thrombin generation with additive increase in peak thrombin when used concomitantly with CFC or BPA.

ADVERSE REACTIONS

Common adverse reactions (incidence ≥10%) are viral infection, nasopharyngitis, and bacterial infection.

Please see accompanying full Prescribing Information, including Boxed WARNING.

REFERENCES

1. Iorio A, Stonebraker JS, Chambost H, et al. Establishing the Prevalence and Prevalence at Birth of Hemophilia in Males: A Meta-analytic Approach Using National Registries. Ann Intern Med. 2019;171(8):540-546. doi:10.7326/M19-1208
2. U.S. Centers for Disease Control and Prevention (CDC). Data and Statistics on Hemophilia. May 15, 2024. Accessed April 28, 2025. https://www.cdc.gov/hemophilia/data-research/index.html.
3. Srivastava A, Santagostino E, Dougall A, et al. WFH Guidelines for the Management of Hemophilia, 3rd edition. Haemophilia. 2020;26(suppl 6):1-158. doi:10.1111/hae.14046
4. Qfitlia Prescribing information. Genzyme Corporation. 2025. https://products.sanofi.us/qfitlia/qfitlia.pdf.
5. Mehta, P, Reddivary AKR. Hemophilia. National Institutes of Health. StatPearls. Updated June 5, 2023. https://www.ncbi.nlm.nih.gov/books/NBK551607/
6. Meeks SL, Batsuli G. Hemophilia and inhibitors: current treatment options and potential new therapeutic approaches. Hematology Am Soc Hematol Educ Program. 2016;2016(1):657-662. doi:10.1182/asheducation-2016.1.657
7. Negrier C, Shima M, Hoffman M. The central role of thrombin in bleeding disorders. Blood Rev. 2019;38:100582. doi:10.1016/j.blre.2019.05.006
8. Machin N, Ragni MV. An investigational RNAi therapeutic targeting antithrombin for the treatment of hemophilia A and B. J Blood Med. 2018;9:135-140. doi:10.2147/JBM.S159297
9. Pasi KJ, Rangarajan S, Georgiev P, et al. Targeting of Antithrombin in Hemophilia A or B with RNAi Therapy. N Engl J Med. 2017;377(9):819-828. doi:10.1056/NEJMoa1616569
10. Young G, et al; for the ATLAS-OLE Trial Group. Safety and efficacy of the fitusiran revised antithrombin-based dose regimen (AT-DR) in people with haemophilia (PwH) A or B, with or without inhibitors (ATLAS-OLE). Presented at: European Association for Haemophilia and Allied Disorders Annual Congress; February 6-9, 2024; Frankfurt, Germany
11. Kenet G, Nolan B, Zulfikar B, et al. Fitusiran prophylaxis in people with hemophilia A or B who switched from prior BPA/CFC prophylaxis: the ATLAS-PPX trial. Blood. 2024;143(22):2256-2269. doi:10.1182/blood.2023021864
12. Data on file CSR. SAR439774-LTE15174

MAT-US-2503836-v1.0-06/2025

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