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Your FAQs Around Hemophilia A

Hemophilia A is a genetic disorder that affects how well your blood clots. With treatment and proactive management, many people with hemophilia A can lead typical, active lives.

Hemophilia is a broad term that describes a group of genetic bleeding disorders caused by a deficiency in certain clotting factors. The type of hemophilia you have depends on the location of the genetic alteration and which clotting factors are affected.

Clotting factors are proteins in your blood. They work together to create clots, an essential part of your healing process that prevents blood loss and sets the foundation for tissue repair.

If your doctor diagnoses you with hemophilia A, learning as much as you can about your condition can help support the success of your long-term management.

Hemophilia A and hemophilia B make up the two primary types of hemophilia. These are genetic conditions that create a deficiency in clotting factors and reduce how well your blood forms clots.

Hemophilia A is due to a genetic alteration to the gene F8 on your X chromosome. When this gene is affected, your body doesn't produce enough clotting factor VIII.

Without enough clotting factor VIII, the clotting process is negatively affected. It can take much longer for your body to form a clot, clots may not form at all, and the clots that do form may not be stable.

The severity of hemophilia A can vary among people. The specific alteration to your F8 gene influences how much clotting factor VIII your body can produce.

In severe hemophilia A, clotting factor VIII is less than 1% or undetectable. Spontaneous bleeding can happen regularly, multiple times a month, from everyday living or unknown causes.

Spontaneous bleeding episodes are internal and can become very painful as blood creates pressure and inflammation in different areas of the body. Your joints, muscles, and mucous membranes are common places for spontaneous bleeding.

In moderate hemophilia A, your body makes slightly more clotting factor VIII. You will still likely experience prolonged bleeding from mild injuries and may have spontaneous bleeding on a monthly or yearly basis.

Mild hemophilia A clotting factor VIII levels range between 5% and 40%. Spontaneous bleeding episodes are rare with this severity of hemophilia A. However, you're still likely to have prolonged or excessive bleeding after mild tissue trauma.

How long someone with hemophilia A lives depends on factors like the severity of their condition, age, overall health, and if they're actively receiving treatment.

While survival rates are improving with treatment, the life expectancy of someone with either hemophilia A or B is still lower than the general population.

A 2023 cohort study found among males with hemophilia A or B, the median age at end of life was 65.5 years, though racial disparities between non-Hispanic Black males (56 years) and non-Hispanic white males (68 years) were significant.

Living with hemophilia A means you have to be careful about bleeding. You'll need to be mindful of the activities you choose to take part in, and you may need to take extra safety precautions before, during, and after participating.

If you play baseball, for example, helmets, face masks, eye protection, and the use of special bases called "breakaway" bases can help prevent injury. You may need to play a specific position to spare your joints.

The severity of hemophilia A and the success of treatment will determine its role in your daily life. If you've received a diagnosis of severe hemophilia A, without treatment, even everyday physical activities can cause spontaneous bleeding in any organ system in your body.

Your doctor will work with you to create an individualized lifestyle guide for managing hemophilia A.

Hemophilia A primarily affects males because it comes from a genetic alteration on the X chromosome. Boys have one X chromosome from their female parent and one Y chromosome from their male parent.

The presence of the Y chromosome dictates male sex. Female sex is determined when a male parent passes on an X chromosome instead of a Y. In other words, males have the XY pairing, and females have the XX pairing.

Because males only have one X chromosome, genetic alterations on that chromosome can affect them more severely. Females have two X chromosomes, so an alteration on one can be offset by the unaltered gene on its pair.

Hemophilia A's effect on your clotting factor VIII levels is determined at birth. It won't change over time.

Hemophilia A symptoms may seem worse with age. However, the changes may be related to natural changes and co-occurring medical conditions that affect the integrity and health of your body's tissues.

The more fragile your blood vessels become from age, for example, the more likely you may be to experience problematic bleeding.

Despite Eye-Popping $3.5 Million Price Tag For Gene Therapy Hemgenix, Budget Impact For Most Payers Will Be Relatively Small

Genetic engineering.

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On November 22nd, the Food and Drug Administration (FDA) approved the world's first gene therapy for hemophilia B; Hemgenix (etranacogene dezaparvovec). Hemgenix will have a list price of $3.5 million per use. This sets a new record for the most expensive single-use gene therapy in the U.S. In spite of the very high price tag, the budgetary impact of the product for most payers will be comparatively small.

The product was first developed by the Dutch biotechnology company uniQure. In 2020, CSL Behring paid $450 million to license the therapy. CSL Behring will be marketing the drug.

Hemophilia B is caused by missing or low levels of a protein called Factor IX, which is needed to clot blood. Depending on the amount of Factor IX present, people with hemophilia B can experience spontaneous or excessive bleeding that can lead to severe health complications. To prevent these complications from occurring, the current standard of care includes treatments consisting of replacement of Factor IX. These must be taken regularly.

Hemgenix's sponsor, CSL Behring, is no stranger to the hemophilia B disease space, as it's been a specialist in plasma and blood-related products for a long time. The company sells two approved Factor IX therapies for hemophilia B.

Hemgenix is designed to replace the gene which is responsible for Factor IX and is defective in people with hemophilia B. Results from the pivotal Phase 3 trial that led to Hemgenix's approval showed that seven to 18 months after infusion, the average adjusted annualized bleeding rate was reduced by 54% compared to baseline. The trial included 54 patients with hemophilia B, 51 of whom (or 94%) were able to discontinue use of prophylaxis and remained free of those routine treatments 18 months of follow-up.

The cost-effectiveness watchdog, the Institute for Clinical and Economic Review (ICER), determined that it would be "fair" for Hemgenix to be priced at or near $2.9 million.

Additionally, ICER noted that a gene therapy such as Hemgenix becomes more cost effective the more durable it is. The company marketing the product, CSL Behring, contends that by reducing costs associated with bleeding and prophylactic infusions, the one-time treatment will save money over time. This is because the current costs of treating people with moderate to severe hemophilia B can be quite significant. For severe hemophilia B patients, for example, over the period of a lifetime the cost can be as much as $20 million per person.

However, at present, it's not known how durable the treatment will be. It's speculation whether the therapy will be "cost saving" as CSL Behring claims.

And, given the churn that exists – the rate at which enrollees leave insurers - many payers in the U.S. May not have a long-term view. That is, they may not be that interested in cost savings that occur for patients years down the road. At the same time, payers will take notice of the high upfront costs per patient.

However, the relatively small sub-population that can be treated with Hemgenix should keep costs in check for most payers. As a rare disease, hemophilia B afflicts approximately 6,000 people in the U.S. About 15% of patients require Factor IX therapy. And only a small portion of these people will be eligible for Hemgenix. In other words, the impact on most payers' budgets - their financial exposure - will be relatively limited.

Estimates of global sales of Hemgenix project $1.2 billion cumulatively through 2026. So, despite its eye-popping price of $3.5 million, this is not a gene therapy that will necessarily break the bank. Moreover, it is likely that value-based pricing arrangements will be implemented which mitigate the impact of the high upfront costs per dose. For example, payers will likely negotiate "milestone-based reimbursement," with installment payments based on (durable) outcomes achieved.

Looking to the future, certain other cell and gene therapies in the pipeline have considerably larger (potentially) eligible populations of patients, including the disease area ischemic stroke. In addition, currently approved cell and gene products in several cancers are now indicated for earlier lines of treatment, which implies substantial expansion of populations suitable for therapy. It's these treatments that (will) hit payer radar screens.

FDA Approves New Treatment For People With Hemophilia B

There's a new hope for people living with the rare blood disorder hemophilia B. 

The FDA recently approved a new gene therapy treatment for those who suffer from the debilitating condition. 

Dave Robinson, a 61-year-old IT consultant from Falls Church, Virginia, was born with the rare genetic blood disorder caused by an insufficient level of a protein known as factor IX. 

That protein helps blood form clots to stop bleeding and seal wounds. Without it, hemophilia B patients bruise easily and bleed more frequently and for longer periods. 

"The biggest problems are caused by doing everyday things that will cause internal bleeding," said Robinson. 

Due to his condition, Robinson would give himself an infusion at home every 10 days. Things changed when he enrolled in a clinical trial and received a single infusion of BEQVEZ, a new Pfizer drug.

BEQVEZ is a one-time treatment that helps patients produce their own factor IX protein to prevent and control bleeding. 

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"It's very exciting. This provides us with an additional tool to treat hemophilia. Not all patients will be candidates for gene therapy, but for those that are good candidates, this is another game changer in their lifetime quality and also their ability to assume normal lives," said Dr. Craig  Kessler, a hematologist with MedStar Georgetown University Hospital. 

"We will have to monitor these patients for at least 15 years to know if there's durability to the gene therapy," he said. "There are others. About 15% of individuals who don't respond adequately to the gene therapy and in the clinical trials had to go back to their clotting factor concentrate regiments." 

Robinson took part in the trial seven years ago, eliminating his need for weekly infusions. 

"I've been able to avoid treating myself 271 times … That burden has been completely removed," he said. 

Since the gene therapy, Robinson has pushed himself to walk 7,000 or 8,000 steps per day, and for the 7,000 Americans living with hemophilia B, that's a huge accomplishment. 

BEQVEZ is approved for those over the age of 18 who meet certain criteria, but doctors still aren't sure what the out-of-pocket cost will be for patients. 

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