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Your FAQs Around Hemophilia A

Many people with hemophilia A can lead ordinary, active lives. Learning more about this genetic condition can support effective long-term management strategies.

Hemophilia A is a genetic condition that is present from birth. It can be inherited or de novo (caused by a genetic change that occurs during embryonic development). Like other types of hemophilia, hemophilia A prevents proper blood clotting.

This article explores the frequently asked questions about hemophilia A, including its causes, severity, and impact on quality of life.

Hemophilia A is one of two primary types of hemophilia — the other is hemophilia B. Hemophilia A is a genetic condition that prevents the body from making enough of clotting factor VIII (factor 8). Clotting factors are proteins in the blood that are involved in coagulation (clot formation).

Clots are part of the body's healing process. They control blood loss and create a matrix that supports tissue repair.

People with hemophilia A have a genetic change on the F8 gene of their X chromosome that affects the production of clotting factor VIII. Without enough clotting factor VIII, coagulation is interrupted. As a result, clots may not form, may form slowly, or may not be stable if they do form.

Hemophilia A varies in severity, depending on how the F8 gene is altered. Genetic changes can result in a mild, moderate, or severe deficiency of clotting factor VIII. The lower the level of clotting factor VIII, the more serious the bleeding can be.

Mild hemophilia A, which involves clotting factor VIII levels of 6% to 40%, rarely causes spontaneous bleeding (episodes of internal hemorrhaging that result from an unknown cause or from everyday activities). Though it is considered mild, this type of hemophilia A will still result in prolonged or excessive bleeding as a result of minor tissue trauma.

Bleeding episodes are more common in severe hemophilia A. With clotting factor VIII levels of less than 1%, severe hemophilia A may periodically cause spontaneous bleeding.

The life span for someone with hemophilia A varies depending on the severity of the condition and on individual factors such as age, co-occurring conditions, and medical management.

Research suggests that hemophilia has an association with a lower life expectancy overall. In a 2020 study involving more than 1,000 men in the Netherlands, researchers found that the median life expectancy for those with hemophilia was 77 years — 6 years lower than the median for the larger population of men.

In a 2023 study in the United States, researchers found that between 1999 and 2020, the median life expectancy for males with hemophilia increased from 54.5 to 65.5 years. However, racial disparities were significant, with a 12-year difference in the median age at end of life between non-Hispanic Black males (56 years) and non-Hispanic white males (68 years).

Quality of life (QoL) is a measurement of how well a person feels. In hemophilia A, QoL varies depending on the severity of the condition and individual variables such as overall health, lifestyle habits, and treatment adherence.

A 2019 survey found that health-related QoL among people with severe hemophilia A was low. The most common challenges that survey participants cited were pain, anxiety, depression, and physical limitations due to joint pain.

QoL in milder forms of hemophilia A may be higher. With treatment and safety measures, many people can maintain ordinary levels of activity and function.

Hemophilia A primarily affects males due to inheritance patterns. The condition appears on the X chromosome.

In females, two X chromosomes are present (XX), one from the father and one from the mother. Males have one X chromosome from their mother and a Y chromosome from their father (XY).

In females, an unaffected X chromosome can compensate for the F8 genetic change on the other X chromosome. However, because males have only one X chromosome, the altered F8 gene will affect the production of clotting factor VIII.

Females can still have factor VIII deficiency if the second X chromosome is not working or if both X chromosomes have the genetic change, but males are more likely to experience severe bleeding.

This means females with an F8 genetic change are less likely to have significant symptoms, while all males with an F8 change for hemophilia A will have clotting factor VIII deficiency.

Clotting factor VIII deficiency in hemophilia A does not worsen with age. If a person does not receive treatment for the condition, the severity that is present at birth will remain consistent throughout the person's life.

However, hemophilia A symptoms may become more noticeable as a result of natural age-related changes in the body, illness, chronic injury, or co-occurring medical conditions. Over time, spontaneous bleeds can cause long-term damage to some areas of the body, such as the joints.

Hemophilia A affects the body's ability to form blood clots. It is a genetic condition caused by a change in the F8 gene on the X chromosome.

With treatment and everyday safety precautions, many people with hemophilia A can lead active, ordinary lives. Quality of life and life expectancy can vary depending on factors such as the condition's severity and a person's age, lifestyle, and co-occurring medical conditions.

Alhemo Approved For Treatment Of Hemophilia A Or B With Inhibitors

The Food and Drug Administration (FDA) has approved Alhemo® (concizumab-mtci) injection for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients 12 years and older with hemophilia A (congenital factor VIII deficiency) with FVIII inhibitors or hemophilia B (congenital factor IX deficiency) with FIX inhibitors.

Concizumab is a tissue factor pathway inhibitor antagonist that enhances factor Xa production during the initiation phase of coagulation. This production improves thrombin generation and clot formation in patients with hemophilia A or B with inhibitors.

The approval is supported by data from the multicenter, open-label phase 3 explorer7 trial (ClinicalTrials.Gov Identifier: NCT04083781), which evaluated the safety and efficacy of concizumab in 133 male patients aged 12 years and older with hemophilia A or B with inhibitors who have been prescribed, or are in need of, treatment with bypassing agents.

The trial consisted of 4 arms (2 randomized and 2 non-randomized). In arms 1 and 2, patients (n=52) previously receiving on-demand treatment were randomly assigned 1:2 to receive no prophylaxis (continue on-demand treatment with bypassing agents) for at least 24 weeks or concizumab prophylaxis for at least 32 weeks, respectively. In arms 3 and 4, additional participants (n=81) were nonrandomly assigned to receive concizumab prophylaxis for at least 24 weeks. The primary endpoint was the number of treated spontaneous and traumatic bleeding episodes measured by annualized bleeding rate (ABR).

Findings showed concizumab-treated patients had an 86% reduction in ABR compared with no prophylaxis (ABR ratio, 0.14; P <.001). The estimated mean ABR was 1.7 for patients treated with concizumab (95% CI, 1.01-2.87) vs 11.8 for patients on no prophylaxis (95% CI, 7.03-19.86).

The most common adverse reactions reported with concizumab were injection site reactions and urticaria.

"The approval of Alhemo® – a first-of-its-kind, prophylaxis, subcutaneous injection pen for adults and children 12 years and older with hemophilia A and B with inhibitors – provides a much needed alternative to the current standard of care in hemophilia B with inhibitors, while offering patients with hemophilia A with inhibitors more treatment options, ultimately providing more patients with inhibitors the opportunity to personalize their care and address current treatment gaps," said explorer7 trial investigator Amy Shapiro, MD, CEO and comedical director at the Indiana Hemophilia & Thrombosis Center, Inc.

Alhemo is supplied as a 60mg/1.5mL, 150mg/1.5mL, or 300mg/3mL single-patient-use prefilled pen for subcutaneous (SC) injection. Patients may self-inject after receiving proper training in SC injection technique.

Nebraska Medicine Administers Novel Gene Therapy To First Hemophilia Patient

After more than four decades of infusing himself with the blood clotting factor his body can't make, Chad Stevens decided it was time to try something new.

Chad Stevens traveled from his home in eastern Idaho in mid-October for an infusion with a gene therapy for hemophilia B at the Nebraska Medical Center. Here, he is overseen by Sarah Steffes, infusion staff nurse lead. The aim is to allow his body to produce enough of the blood clotting factor it can't make now to reduce his need to infuse it.

TAYLOR WILSON, NEBRASKA MEDICINE

Stevens, 63, suffers from hemophilia B, a bleeding disorder caused by a genetic mutation that affects production of a type of protein known as factor 9. Over the years, bleeds have damaged his joints. His ankles have been fused, his knees and elbows have severe damage. And successfully hitting a vein to infuse himself as he got older wasn't getting any easier.

In mid-October, Stevens traveled from his home town of Newdale, Idaho, to Omaha's Nebraska Medical Center, where he became the hospital's first patient to receive the first gene therapy approved for his condition.

Called Hemgenix, the therapy doesn't fix the damaged gene. Instead, a modified virus delivers the working gene to the liver, providing the instructions his body needs to make the factor on its own. The medical center is the first hospital in the region to become an administration site for the therapy, according to drug-maker CSL Behring.

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Since then, Stevens hasn't had any bleeds or needed to infuse clotting factor. He said he hopes the therapy will provide enough to take him from severe hemophilia to a milder version that might require infusions only for a severe trauma or surgery.

"That's really promising," Stevens said. "I hate to get too excited about it, because you never know what's going to happen. But I'm quite thrilled with it."

So is Dr. Alex Nester, a hematologist with Nebraska Medicine who specializes in benign or non-cancerous blood conditions, including bleeding disorders and sickle cell disease.

"It's incredible," he said. "It's (been) a dream in the hemophilia community for 20-plus years."

The treatment, approved by the Food and Drug Administration in 2022, is one of a number of gene therapies that have trickled out in recent years for a variety of genetic conditions. The FDA approved a separate gene therapy for hemophilia A last year. The agency also has approved two gene therapies for sickle cell disease, another inherited blood disorder that causes red blood cells to become misshapen, block blood flow and cause painful episodes.

Kim Phelan, CEO of The Coalition for Hemophilia B, said the lasting advantages of the gene therapy include reduced joint damage, fewer hospitalizations and a better quality of life for people with hemophilia.

An estimated 7,000 people in the U.S. Have hemophilia B, and approximately 17,000 have hemophilia A, which involves a different blood clotting factor.

"After more than 25 years of anticipation and hope, individuals with hemophilia now have access to a groundbreaking therapy that offers the potential for greater independence and a more normalized life," she said.

Gene therapy at Nebraska Medicine

At Nebraska Medicine, the addition of the gene therapy builds on the work of the team involved in bone marrow transplants and cellular therapies, including CAR-T, or chimeric antigen receptor T-cell therapy. That treatment involves removing patients' immune cells from their bodies and genetically engineering them to recognize and attack their cancer.

Chad Stevens, left, of Newdale, Idaho, speaks with Dr. Alex Nester, a hematologist with Nebraska Medicine. Stevens traveled to the Nebraska Medical Center in mid-October to receive a gene therapy for hemophilia B. Since then, he has suffered no bleeds and has not had to use the clotting factor he has routinely infused to prevent bleeding.

TAYLOR WILSON, NEBRASKA MEDICINE

Dr. Matthew Lunning, medical director of gene and cellular therapy at Nebraska Medicine, said earlier this fall that the team has used CAR-T to treat hundreds of lymphoma and leukemia patients since the late 2010s.

Earlier this year, he and his team used CAR-T for the first time to treat an Omaha woman with lupus, an autoimmune disease, as part of a multi-site clinical trial. He credited Nebraska Medicine's leaders for making the investment required to offer such ground-breaking therapies.

Still, gene therapies, according to news reports, have been somewhat slow to catch on. In the case of hemophilia, Nester said he suspects that may be a result of the complex modern history of the condition.

By the 1980s, he said, hemophilia patients who suffered trauma were given a concentrated form of the missing proteins when they needed help getting their blood to clot. But many contracted infections such as HIV and hepatitis C from contaminated blood products, which killed thousands of those with severe disease. Later, the products were purified but still were reserved for cases of active bleeding. As a result, older patients like Stevens suffered significant joint damage.

In the 1990s, researchers began producing a recombinant version of the missing proteins in hamster cells, similar to the way insulin is made. Children diagnosed with hemophilia could dose themselves with clotting factors to prevent bleeds, he said. That resulted in a generation with no bleeding episodes for years at a time and without the joint damage suffered by older patients.

"You don't need a lot of these factors to live a pretty normal life," said Nester, also an assistant professor of medicine in UNMC's oncology and hematology division.

Chad Stevens of Newdale, Idaho, is infused with a gene therapy for hemophilia B at the Nebraska Medical Center in mid-October.

TAYLOR WILSON, NEBRASKA MEDICINE

That also means younger patients may have less interest for now in a more permanent solution, he said. Some also may be holding off for newer versions of the gene therapy that are in the pipeline.

Stevens said his parents, on the other hand, were told he probably wouldn't survive his teens. Between his mother and her three sisters, three had children with hemophilia, a total of seven. He was the youngest. He is now the sole survivor. Several died from bleeds and a couple died of complications of AIDs due to the contaminated clotting factor relied on at the time.

"It took a big toll on the hemophilia community," he said. "It just decimated it, really. So us older ones are pretty lucky to have survived all of that."

Issues with earlier blood products, however, also have made older patients skeptical about new treatments. "We like to wait and see how the products are doing out there before you jump on it," he said.

Cost of treatment can run into the millions

Patients also have to weigh the cost. The price for the one-time treatment reportedly was set at $3.5 million.

A spokesperson for CSL Behring said the company has seen an acceleration in the number of people being infused with the therapy since its approval, which the company attributes to its outreach to patients and work with insurers. Some 90% now cover the therapy, and the company also offers a program to help patients with copays. She declined to say, however, how many patients have received the therapy.

But Nester said clotting factors also are costly. Depending on the patient, the source of their factor and their insurance, it may run a half a million dollars a year "to keep nothing from happening," he said.

Meanwhile, he said, researchers have seen that the majority of patients who have received the gene therapy are making 10% or more of the normal levels of the missing clotting factor even five years after being treated. That means their bodies are producing at least the preventative dose.

"Patients still may have a bleeding episode after twisting their ankle or maybe needing a dose before surgery," Nester said, "but, generally speaking, spontaneous bleeds or bleeds associated with minor trauma are gone."

Not every hemophilia patient will qualify for the treatment, however, he said. Patients can't have antibodies to either the virus or the factor they're missing.

Stevens said his infusions probably cost closer to three-quarters of a million dollars a year. So far, the cost of his gene therapy has been covered. Previously employed in banking in Boise, he retired and applied for Social Security disability benefits on the advice of his doctor after his pain and mobility issues had made it nearly impossible for him to get out of his chair at work.

He moved back to Newdale, population 325, in eastern Idaho. But he didn't like being on disability, because he wasn't giving back. He was elected to the City Council and appointed mayor, a post he continues to hold.

"It was just a pleasure to be contributing again," Stevens said.

Since receiving the therapy, he said, he seems to be moving a little better, and his knee isn't bothering him as much. Since the damage was done at an earlier age, he doesn't think the therapy will do much to repair it.

"But if we can keep it from getting any worse," Stevens said, "that's the goal."

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