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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 Once-Daily Treatment For Hemophilia A, B With Inhibitors FDA Approved

The FDA recently approved the treatment by Novo Nordisk for hemophilia A or B with inhibitors, designed to prevent or reduce bleeding episodes in patients aged 12 and older.

The FDA recently approved Novo Nordisk's Alhemo (concizumab-mtci), the first subcutaneous, once-daily treatment for hemophilia A or B with inhibitors, designed to prevent or reduce bleeding episodes in patients aged 12 and older.

The drug targets the tissue factor pathway inhibitor (TFPI), which can prevent blood from clotting properly, according to a release by Novo Nordisk. By blocking TFPI, Alhemo increases the production of thrombin, a protein essential for blood clotting, which reduces the frequency of bleeding episodes in patients with inhibitors.

This treatment addresses a critical need for those with hemophilia.

For instance, 30% of patients with severe hemophilia A and 5% to 10% of those with severe hemophilia B develop inhibitors, which complicates their condition. For those with hemophilia B and inhibitors, treatment options are especially limited.

The FDA granted Breakthrough Therapy designation to Alhemo based on results from Phase 2 clinical trials.

Anna Windle, senior vice president of Clinical Development at Novo Nordisk, said, "The approval of Alhemo signifies a remarkable achievement in prophylactic hemophilia treatment for individuals with inhibitors aged 12 years and older who, in some cases, currently have few options."

Many current treatments for hemophilia A or B with inhibitors require intravenous infusions, which can be difficult and time-consuming.

Alhemo uses a prefilled, premixed pen for subcutaneous injection with a thin 32-gauge, 4-mm needle. This makes the treatment process easier and less invasive.

Hemophilia is a rare genetic disorder that affects the body's ability to form blood clots due to a lack of clotting factors. This condition can cause prolonged bleeding after injuries, surgeries or random bleeding episodes in muscles, joints and organs, which can become life-threatening if not managed effectively.

Inhibitors can add another layer of challenges to treating hemophilia. These are antibodies that block the activity of clotting factors, making traditional therapies less effective.

In the U.S., around 33,000 males live with hemophilia, with Hemophilia A making up 80% to 85% of cases. Approximately 30% of patients with hemophilia A and 5-15% of those with hemophilia B develop inhibitors.

Clinical trials have shown Alhemo to be both effective and safe. For example, in a Phase 3 trial with 133 male patients with hemophilia A or B with inhibitors, researchers compared bleeding episodes between patients using Alhemo and those without prophylaxis.

The results showed an 86% reduction in the annualized bleeding rate for those on Alhemo.

Common side effects reported in clinical trials include injection site reactions and hives, skin redness, rash, itching and abdominal pain. It's suggested that patients with a history of severe allergic reactions to Alhemo or its ingredients should avoid using it. The treatment also carries a risk of blood clots, so careful monitoring is critical.

While the cost of the drug has not yet been fully disclosed, the average yearly cost of hemophilia medication can exceed $393,000 per patient. Hemophilia treatment costs vary depending on factors such as how often a patient experiences bleeding episodes and how much treatment they need for each episode, according to Evernorth Health Services.

Alhemo offers a new way to manage hemophilia A or B with inhibitors. It makes treatment more efficient and helps solve some of the challenges that come with the condition, giving patients more options for their care.

First Subcutaneous Prophylaxis For Hemophilia A And B With Inhibitors Approved By FDA

The approval of concizumab-mtci (Alhemo) injection marks a significant milestone in managing hemophilia A and B with inhibitors by preventing or reducing bleeding episodes in adults and children 12 years and older.

The FDA approved concizumab-mtci (Alhemo) injection for the prevention or reduction of bleeding episodes in adults and children aged 12 years and older with hemophilia A or B with inhibitors, according to an announcement from Novo Nordisk.1 With daily subcutaneous (SC) administration, the therapy offers treatment for a patient population with limited prophylactic options.

Inhibitors affect an estimated 30% of patients with severe hemophilia A and up to 10% of those with severe hemophilia B, complicating treatment.

Image Credit: Deni-stock.Adobe.Com.Jpeg

Traditionally, hemophilia with inhibitors has been managed with intravenous (IV) infusions; concizumab shifts the paradigm with a subcutaneous injection that offers improved convenience and efficacy. SC injections offer several advantages over IV and intramuscular methods, primarily due to their ease of use and lower risk of complications.2

"Alhemo signifies a remarkable achievement in prophylactic hemophilia treatment for individuals with inhibitors," Anna Windle, senior vice president of Clinical Development at Novo Nordisk, said in the statement.1 "This innovative approach addresses significant unmet needs, offering patients the opportunity to personalize their care."

The FDA's decision was based on data from the pivotal phase 3 explorer7 trial, which demonstrated an 86% reduction in treated spontaneous and traumatic bleeds in patients on concizumab prophylaxis compared with no prophylaxis. The results revealed an annual bleeding rate (ABR) of 1.7 in treated patients, compared with 11.8 in the control group. Additionally, 64% of patients receiving concizumab experienced no treated bleeds during the first 24 weeks of treatment.

Concizumab is a tissue factor pathway inhibitor (TFPI) antagonist designed to enhance thrombin production by blocking TFPI—a protein that disrupts blood clotting. Doing so helps patients with hemophilia produce the clots necessary to prevent excessive bleeding, even in the presence of inhibitors that make standard clotting factor replacement therapies ineffective.

Inhibitors affect an estimated 30% of patients with severe hemophilia A and up to 10% of those with severe hemophilia B, complicating treatment. For these patients, uncontrolled bleeding remains a life-threatening risk. Concizumab offers a new option, especially for individuals with hemophilia B, who have historically faced the greatest challenges due to limited prophylactic therapies.

"The development of inhibitors is the most serious treatment-related complication for people living with hemophilia," Amy Shapiro, MD, CEO of the Indiana Hemophilia & Thrombosis Center, stated. "Alhemo provides a much-needed alternative, ultimately addressing gaps in care and expanding options for personalized treatment."

In addition to the US, concizumab-mtci has been approved in Australia, Japan, Switzerland, and the EU, with indications varying by country. The product's user-friendly design—a prefilled, premixed pen with a thin needle—indicates a patient-centric approach, according to Novo Nordisk.

The company's news release expressed hopes that by providing a safer, more effective, and easier-to-administer prophylactic option, the treatment has the potential to significantly improve the quality of life for individuals living with hemophilia A and B with inhibitors.

References

1. FDA approves Alhemo injection as once-daily prophylactic treatment to prevent or reduce the frequency of bleeding episodes for adults and children 12 years of age and older with hemophilia A or B with inhibitors. News release. Novo Nordisk. December 20, 2024. Accessed December 23, 2024. Https://www.Novonordisk-us.Com/media/news-archive/news-details.Html?Id=915084

2. Usach I, Martinez R, Festini T, Peris JE. Subcutaneous injection of drugs: literature review of factors influencing pain sensation at the injection site. Adv Ther. 2019;36(11):2986-2996. Doi:10.1007/s12325-019-01101-6

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