Fig. 1: Phenotypic and dysmorphic features of patient 1 (A and B),...

A Reality Check Of Hemophilia Care: What A Real-World Study Says About The Unmet Needs Of People With Hemophilia A Or B

Results of a real-world study that included people with hemophilia from 33 countries show that people with hemophilia B, especially those with inhibitors, have the greatest unmet need.

Despite advancements and novel therapies, unmet needs persist in hemophilia management, according to an article in the journal Haemophilia. The needs are particularly notable in achieving effective disease control, especially for patients with hemophilia B with antibodies against clotting factor IX that limits effective prophylaxis options.

Allison Wheeler, M.D., an attending physician at Seattle's Children's Hospital and the Washington Center for Bleeding Disorders, and her co-authors noted patients with hemophilia face a significant burden of disease, which includes compromised joint health, chronic joint pain, reduced physical activity levels and diminished health-related quality of life (HRQoL). Much of the burden can be attributed to musculoskeletal damage from frequent bleeding episodes.

The goal of hemophilia treatments is to prevent bleeding episodes and associated long-term joint damage. Prophylaxis with coagulation factors is recommended by current guidelines, particularly for patients with severe hemophilia, because of demonstrated superiority over episodic (on-demand) treatment in reducing bleeding tendencies and long-term complications. However, costs and socioeconomic circumstances result in many patients resorting to on-demand treatment.

Wheeler and her co-authors highlighted the added complexity to hemophilia management when it comes to therapies. Weekly intravenous injections of coagulation factor replacement have its challenges. It's a time-intensive practice associated with injection pain. Additionally, the development of antibodies — sometimes called inhibitors — that can neutralize infused factor VIII, the prophylactic treatment for hemophilia A, and factor IX, the prophylactic treatment for hemophilia B. Patients who develop antibodies often have limited treatment options, leading to a higher disease burden and reduced HRQoL

A real-world look

Given the disease burden, the challenges with inhibitors, and the need for better treatment options, there is a need to evaluate real-world data from patients with hemophilia to better understand existing unmet needs and potentially improve healthcare outcomes. Wheeler and her team conducted the explorer6 study, a prospective, noninterventional study across 33 countries that aimed to assess the real-world unmet needs of patients with hemophilia A and hemophilia B, both with and without inhibitors.

For the study, male patients age 12 and older were included if they had severe hemophilia A or hemophilia B, with or without inhibitors. The primary end point was the number of bleeding episodes from enrollment up to a maximum of 115 weeks during routine clinical treatment practice. The bevy of secondary end points examined physical activity levels measured by a wrist-worn physical activity tracker, the number of treated spontaneous bleeding episodes, treated traumatic bleeding episodes, treated joint bleeding episodes and target joint assessment using the Hemophilia Joint Health Score (HJHS) measurements. A target joint was defined as a single joint with at least 3 spontaneous bleeding episodes.

The number of bleeding episodes over the course of the study or annualized bleeding rates were found to be, on average, less frequent for patients with hemophilia A, hemophilia B or hemophilia A with inhibitors receiving prophylaxis treatment compared to on-demand treatment. When comparing annualized bleeding rates by hemophilia type, numerically lower rates were observed among patients with hemophilia A or hemophilia B receiving prophylaxis versus either type of hemophilia with inhibitors. Lastly, annualized bleeding rates were also reported for treated spontaneous, traumatic, joint, and target joint bleeding episodes. Those results show lower rates with prophylaxis compared with on-demand for both types of hemophilia and hemophilia A with inhibitors.

Physical activity levels (light, moderate, and vigorous) were collected using a wrist-worn physical activity tracker for most patients (95.7%), where data was recorded as a mean percentage of awake time. The majority of awake time was measured as light physical activity, and a smaller percentage was measured as moderate to vigorous physical activity. The tracker measured comparable levels of physical activity for prophylaxis and on-demand patients within each group. Among all patients, those with hemophilia B and inhibitors exhibited the lowest levels of measured physical activity. This aligns with the expectation that patients with hemophilia often experience joint pain and reduced physical activity.

Mean and median HJHS total scores were available for 130 (56.3%) patients where 52.4% of patients reported target joints, most commonly in the knee (54.5%), elbow (50.4%) and ankle (37.2%). The mean number of target joints per patient ranged from 1.3 to 2.3 across all groups. Lower HJHS total scores indicate better joint health and the mean and median HJHS total scores were generally lower for patients receiving prophylaxis compared to on-demand treatment for both types of hemophilia and hemophilia A with inhibitors.

The study highlighted that significant unmet needs persist, particularly for patients receiving on-demand treatment and those with inhibitors, especially hemophilia B with inhibitors. Patients receiving on-demand treatment experienced higher bleeding rates and poorer joint health compared to many on prophylaxis.

Wheeler and her co-investigators concluded that "it is evident that unmet needs, in particular the management of bleeding episodes, joint health and physical activity, remain for patients receiving on-demand treatment and patients with inhibitors, and these are even more substantial for those with HBwI [hemophilia B with inhibitors] for whom no efficacious prophylaxis treatment regimen is available."

Qfitlia, A Novel Treatment For Hemophilia A Or B, Gets FDA Approval

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FDA Approves Novel Treatment For Hemophilia A Or B, With Or Without Factor Inhibitors

Medication Can be Given Up to Once Every 2 Months

SILVER SPRING, Md., March 28, 2025 /PRNewswire/ -- Today, the U.S. Food and Drug Administration approved Qfitlia (fitusiran) for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients 12 years of age and older with hemophilia A or hemophilia B, with or without factor VIII or IX inhibitors (neutralizing antibodies).

"Today's approval of Qfitlia is significant for patients with hemophilia because it can be administered less frequently than other existing options," said Tanya Wroblewski, M.D., deputy director of the Division of Non-Malignant Hematology in the FDA's Center for Drug Evaluation and Research. "This new treatment option highlights our continued efforts to improve the lives of patients with hemophilia."

Hemophilia A and hemophilia B are genetic bleeding disorders caused by a dysfunction or deficiency of coagulation factor VIII (FVIII) or IX (FIX), respectively. Patients with these hemophilias are unable to clot properly and may bleed for a longer time than normal after injury or surgery. They may also have spontaneous bleeding in muscles, joints and organs, which can be life-threatening. These bleeding episodes are typically managed by either on-demand, episodic treatment or prophylaxis using products containing FVIII or FIX, or a product that mimics a factor.

Qfitlia does not replace the missing clotting factor. Rather, it reduces the amount of a protein called antithrombin, leading to an increase in thrombin, an enzyme critical for blood clotting.

Qfitlia is administered under the skin (subcutaneously) starting once every two months. The dose and frequency of injections are adjusted using the FDA-cleared INNOVANCE Antithrombin companion diagnostic test. This companion diagnostic is intended to monitor and—by informing dosing and frequency of injections—achieve antithrombin activity in the target range to reduce the risk of bleeding and to reduce the risk of excessive blood clotting. The FDA granted clearance of the INNOVANCE Antithrombin test to Siemens Healthcare Diagnostics GmbH.

Qfitlia's efficacy and safety were assessed in two multicenter, randomized clinical trials which enrolled a total of 177 adult and pediatric male patients with either hemophilia A or hemophilia B. In one study, participants had inhibitory antibodies to FVIII or FIX and previously received on-demand treatment with medicines known as "bypassing agents" for bleeding. In the second study, participants did not have inhibitory antibodies to FVIII or FIX and previously received on-demand treatment with clotting factor concentrates. In the two randomized trials, participants received either a fixed dose of Qfitlia monthly or their usual on-demand treatment (bypassing agents or clotting factor concentrates) as needed for nine months. The fixed dose of Qfitlia is not approved because it led to excessive clotting in some patients.

Story Continues

Participants subsequently entered a long-term extension study in which they received an adjustable dose of Qfitlia based on periodic measurements of antithrombin activity. This antithrombin-based dosing regimen is the approved dosage regimen. Efficacy of Qfitlia using the antithrombin-based dosing regimen was established by comparing patients on this dosing regimen of Qfitlia during the long-term extension study to the on-demand control data from the two randomized clinical trials.

The primary measure of efficacy of Qfitlia was the estimated annualized bleeding rate of treated bleeds. In the participants with inhibitors who received the antithrombin-based dosing regimen of Qfitlia, there was a 73% reduction in estimated annualized bleeding rate compared to those who received on-demand treatment with bypassing agents. In participants without inhibitors who received the antithrombin-based dosing regimen of Qfitlia, there was a 71% reduction in estimated annualized bleeding rate compared to those who received on-demand treatment with clotting factor concentrates.

Qfitlia has a boxed warning for thrombotic events (blood clotting) and gallbladder disease (with some patients requiring gallbladder removal). Qfitlia also has a warning about liver toxicity and the need to monitor liver blood tests at baseline and then monthly for at least six months after initiating treatment with Qfitlia or after a dose increase of Qfitlia.

The most common side effects of Qfitlia are viral infection, common cold symptoms (nasopharyngitis) and bacterial infection.

The FDA granted Qfitlia Orphan Drug and Fast Track designations for this application.

The FDA granted the approval of Qfitlia to Sanofi.

Media Contact: Chanapa Tantibanchachai, 202-384-2219Consumer Inquiries: Email or 888-INFO-FDA

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation's food supply, cosmetics, dietary supplements, radiation-emitting electronic products, and for regulating tobacco products.

 

(PRNewsfoto/U.S. Food and Drug Administration)

 

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SOURCE U.S. Food and Drug Administration

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