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HEMGENIX® (etranacogene dezaparvovec-drlb) is being administered across the U.S.

Andrea shares her experience treating people with HEMGENIX gene therapy

This is a paid public announcement from CSL Behring and does not constitute an endorsement of products or services. When you click on the links in this blog entry, you will be directed to the CSL Behring website. LA Kelley Communications always advises you to be a savvy consumer when contacting any company; do not reveal identifying information against your will.

Andrea, APNP, works at a center in Wisconsin, and has administered HEMGENIX gene therapy to some of the first people in the U.S. following FDA approval. Andrea also currently sits on the Region V-West Regional Council and Regional Gene Therapy Working Group.

We recently caught up with Andrea to talk about her experience treating people with HEMGENIX, and highlights from our discussion follow.

Please note that Andrea is sharing her patients’ experiences and others’ experiences may vary.

Andrea Buxton, APNPHi Andrea, let’s start with the news everyone wants to hear. What results have you seen in the people you treated with HEMGENIX?

The people I’ve treated have been early responders—their factor IX levels started coming up after the first week, and they have been able to stop prophylaxis after week two.

Patients almost a year out are still experiencing fantastic results. They’ve remained off prophylaxis. They’ve had some injuries that in the past would have caused a bleed, but none required any factor IX infusions.

How did your team identify the patients you would end up treating with HEMGENIX?

We looked primarily at people with hemophilia B on prophylaxis therapy that were still having bleeds, but we wanted all who were potentially eligible to be made aware that it’s a new option for them.

Those we treated were born with hemophilia B, were very afraid of needles, still experienced bleeds, and even as young men they had identified target joints. Also, they were very motivated and excited to know that there was a treatment option that could potentially improve their quality of life.

We went over the clinical data and the risk of adverse events that could occur. We sent them home with written information and said we would be following up with them.

Did any patients have any issues or concerns?

They were looking at this therapy as something that could potentially really change things for them. And what if it didn’t work? I told them that while we don’t know how every person will react, the data that we do have is reassuring. And in the clinical trial, we know reasons why it did not work for specific people. (Of the 54 people in the trial, 2 experienced lack of efficacy. One person had a high neutralizing antibody titer of 1:3212, and 1 person received about 10% of the planned dose.)

What is your eligibility process leading up to Infusion Day?

It is about a 4-month process from the time our patients decide they want to move forward with HEMGENIX until Infusion Day.

For the patients we’ve treated at the center, we completed an initial consent form and brought them in right away to do their AAV5 neutralizing antibody testing. Even though this wouldn’t have excluded them, we wanted to make sure they didn’t have abnormally high levels. We set up their labs and their liver diagnostics in the interim and chose to do a psychosocial assessment.

While that is going on, we work with both CSL Behring and the HEMGENIX ConnectSM program on the financial side for coverage. We make sure there is great communication between the clinical team and the financial team. Our patients have found the HEMGENIX Connect program helpful with the benefits investigation and providing education on CSL Behring’s travel assistance program.

That brings us to your Infusion Days! What have those been like?

Infusion Days have been very exciting!

Our policy for anyone undergoing gene therapy is to visit us the day before for one final check-in. They stay in town overnight, and then arrive the next morning, ready for their infusions. I think most people will say there may be a few nerves when you’re doing a new therapy, but I don’t think we could have asked for better days for their infusions. We have not had any infusion reactions, and when the patients have finished there have been lots of hands in the air and cheers.

We have our patients stay in town overnight for a follow-up visit the next day just to make sure things are going well. We then provide them with calendars with their weekly lab monitoring for the next 3 months and choose to send them home with steroids in the event they would need them. They have had some liver enzyme elevations and took steroids to bring those levels back down.

That follow-up visit is really important to go through what’s next for them.

Where do post-monitoring visits take place?

If a person lived quite a distance away, we did all of their baseline labs at the hospital we knew they would be using so that we could keep labs very consistent. We also did monthly video visits with them so we could track their progress.

If another person chose to come to our center for all of their labs, we did that as well. And if there were a few times where they were traveling for work, we did have to send orders to a different location. We were able to set it all up pretty easily.

What did the people you treated tell you was the biggest difference they felt since Infusion Day?

They always say they can’t believe they’ve gone this long without a factor IX infusion. Patients have had some injuries in that time frame—either getting a finger caught in the car door or slicing a thumb with a knife—and they expressed a little bit of shock over the fact that those injuries didn’t bleed like they did prior to HEMGENIX.

If someone with hemophilia B is considering HEMGENIX, what advice would you give them?

I would advise talking with every person with hemophilia B about their quality of life. What their goals are for themselves and their bleeding disorder, and making sure they know there is this option out there that could help them meet those goals.

There are great resources from CSL Behring for you, and now that other healthcare providers like our center have gone through the process, I’m sure they’re willing to answer questions too.

And that joy you see in a person when you tell them that they’re making their own factor IX level is well worth it!

IMPORTANT SAFETY INFORMATION

What is HEMGENIX?

HEMGENIX®, etranacogene dezaparvovec-drlb, is a one-time gene therapy for the treatment of adults with hemophilia B who:

  • Currently use Factor IX prophylaxis therapy, or
  • Have current or historical life-threatening bleeding, or
  • Have repeated, serious spontaneous bleeding episodes.

HEMGENIX is administered as a single intravenous infusion and can be administered only once.

What medical testing can I expect to be given before and after administration of HEMGENIX?

To determine your eligibility to receive HEMGENIX, you will be tested for Factor IX inhibitors. If this test result is positive, a retest will be performed 2 weeks later. If both tests are positive for Factor IX inhibitors, your doctor will not administer HEMGENIX to you. If, after administration of HEMGENIX, increased Factor IX activity is not achieved, or bleeding is not controlled, a post-dose test for Factor IX inhibitors will be performed.

HEMGENIX may lead to elevations of liver enzymes in the blood; therefore, ultrasound and other testing will be performed to check on liver health before HEMGENIX can be administered. Following administration of HEMGENIX, your doctor will monitor your liver enzyme levels weekly for at least 3 months. If you have preexisting risk factors for liver cancer, regular liver health testing will continue for 5 years post-administration. Treatment for elevated liver enzymes could include corticosteroids.

What were the most common side effects of HEMGENIX in clinical trials?

In clinical trials for HEMGENIX, the most common side effects reported in more than 5% of patients were liver enzyme elevations, headache, elevated levels of a certain blood enzyme, flu-like symptoms, infusion-related reactions, fatigue, nausea, and feeling unwell. These are not the only side effects possible. Tell your healthcare provider about any side effect you may experience.

What should I watch for during infusion with HEMGENIX?

Your doctor will monitor you for infusion-related reactions during administration of HEMGENIX, as well as for at least 3 hours after the infusion is complete. Symptoms may include chest tightness, headaches, abdominal pain, lightheadedness, flu-like symptoms, shivering, flushing, rash, and elevated blood pressure. If an infusion-related reaction occurs, the doctor may slow or stop the HEMGENIX infusion, resuming at a lower infusion rate once symptoms resolve.

What should I avoid after receiving HEMGENIX?

Small amounts of HEMGENIX may be present in your blood, semen, and other excreted/secreted materials, and it is not known how long this continues. You should not donate blood, organs, tissues, or cells for transplantation after receiving HEMGENIX.

Please see full prescribing information for HEMGENIX.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

You can also report side effects to CSL Behring’s Pharmacovigilance Department at 1-866-915-6958.

HEMGENIX is manufactured by uniQure Inc. and distributed by CSL Behring LLC.
HEMGENIX® is a registered trademark of CSL Behring LLC.
HEMGENIX ConnectSM is a service mark of CSL Behring LLC.
©2024 CSL Behring LLC 1020 First Avenue, PO Box 61501, King of Prussia, PA 19406-0901 USA

www.CSLBehring.com   USA-HGX-0695-APR24

Explore the truths of people living with hemophilia (PwH) and change the conversation

This is a paid public announcement from Sanofi and does not constitute an endorsement of products or services. When you click on the links in this blog entry, you will be directed to the Sanofi website. LA Kelley Communications always advises you to be a savvy consumer when contacting any company; review opt-in language from any company website before sharing any identifying information.

PwH know how much work goes into managing the physical effects of their condition, but are there unseen impacts that PwH may not share broadly?

We were curious about how PwH really felt, so we brought 8 individuals together to share their hemophilia truths, and this is what we learned.

The many moving stories we heard brought a simple truth to light; hemophilia management can have a daily impact on mental health, family life, and the ability to explore other aspects of their identity. Kyle, one of the individuals we spoke to, shared the following about his experience growing up with hemophilia: “I was told, ‘No playing sports; you should be bubble wrapped.’” Have you ever felt limited by hemophilia, like Kyle? If so, you’re not alone.

Let’s discover some truths: what kind of unseen impacts are other PwH facing?
For many people living with hemophilia, the burden goes beyond the bleed. They may experience emotional, physical, and logistical challenges before, during, and even after bleeding episodes.

Emotional challenges
Many PwH have demanding treatment schedules that may disrupt their daily lives. Missing school, work, social and recreational opportunities, and more can have a negative impact on their mental health and lead to feelings of social isolation.

PwH may also experience negative impacts on their self-perception, social lives, and relationships.

Physical challenges
PwH live with daily concerns about their levels of bleed protection and are often aware of their vulnerability to breakthrough bleeds.

PwH may also periodically experience varying degrees of pain due to bleeding events and accumulated joint damage.

Logistical challenges
Management of hemophilia can come with logistical demands such as refrigeration requirements, the need for reconstitution, difficulties with scheduling treatment, and traveling to their treatment centers. These types of logistical considerations can make daily life more difficult for PwH.

Have you been sharing your whole truth with your healthcare provider (HCP)? Speaking your whole truth can help you and your HCP:
  • –    Better understand the daily unseen impact of hemophilia
  • –    Improve your hemophilia management and help you meet your individual goals
  • –    Educate PwH and caregivers about hemophilia and its various treatment approaches
Are there any of these challenges that resonate with you that you might not have shared openly? It’s time to consider your whole experience with hemophilia and change the conversation.

Are you ready to change the conversation?
Discover more truths and how you can address your whole experience at MyHemophiliaTruth.com

© 2024 Genzyme Corporation. All rights reserved. Sanofi is a registered trademark of Sanofi or an affiliate. All other trademarks are the property of their respective owners. MAT-US-2400561-v1.0-02/2024

Is it time to FACTOR UP your hemophilia A management?

This is a paid public announcement from Sanofi and does not constitute an endorsement of products or services. When you click on the links in this blog entry, you will be directed to a Sanofi website. LA Kelley Communications always advises you to be a savvy consumer when contacting any company; do not reveal identifying information against your will.

Living with hemophilia A often means learning to live with unknowns—painful bleeds that can happen without warning, not knowing when a bleed might interrupt your plans, or when juggling treatment needs interrupts juggling, well, life itself.

But recent treatments may be able to change some of that—like ALTUVIIIO [antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl]. In 2023, Sanofi received FDA approval for ALTUVIIIO, a first-in-class Factor VIII replacement therapy that provides proven bleed protection for longer with once-weekly prophylaxis.

Here are 4 reasons to consider ALTUVIIIO:

  1. HIGHER SUSTAINED FACTOR LEVELS

ALTUVIIIO is engineered to last longer. With just one weekly infusion, Factor VIII levels remain in the near-normal to normal range (over 40%) for most of the week and stay above 18%,* on average, in adults.

*Average trough levels were 18% for adults 18 years and older, 9% for adolescents aged 12 years to under 18 years, 10% for children aged 6 years to under 12 years, and 7% for children aged 1 year to under 6 years.

†This is information from a study in 13 previously treated adults with severe hemophilia A that had the goal of comparing how long ALTUVIIIO, Adynovate® [Antihemophilic Factor (Recombinant), PEGylated], and Advate® [Antihemophilic Factor (Recombinant)] stayed in the body after 1 dose. Half-life was 43 hours for ALTUVIIIO, 15 hours for Adynovate, and 11 hours for Advate.
Adynovate and Advate are registered trademarks of Baxalta Incorporated, a Takeda company.
EHL=extended half-life; SHL=standard half-life.

ALTUVIIIO can be used not only for weekly prophylaxis but also for on-demand bleed control and perioperative management. Regardless of how you use it, you can expect the same infusion process

  1. STUDIED—AND PROVEN—BLEED PROTECTION

 Before we dive into the data, it’s helpful to know how ALTUVIIIO was studied and to understand its safety profile.

For one year, the XTEND-1 study looked at treatment in 159 adults and adolescents. Participants were divided into 2 groups. Both groups used mean and median annualized bleed rates (ABRs) to evaluate the efficacy of ALTUVIIIO. Finding people’s mean ABR was the primary goal of the study.

Safety evaluated in 159 people taking ALTUVIIIO in the XTEND-1 study showed that:

  • 21% of people had headache (33 people)
  • 16% of people had joint pain (26 people)
  • 6% of people had back pain (9 people)

ALTUVIIIO was also studied in the XTEND-Kids trial, in 67 previously treated male children under the age of 12. These children all received at least 1 dose of ALTUVIIIO.

In 67 children taking ALTUVIIIO in the XTEND-Kids study at the time of the interim analysis:

  • 1% of children had headache (1 child)

In XTEND-1 and XTEND-Kids, people taking ALTUVIIIO had:

  • 0 inhibitors
  • 0 serious allergic reactions

Although no inhibitors were found, and no serious allergic reactions occurred in clinical studies, inhibitors and serious allergic reactions are possible with ALTUVIIIO.

Group 1

This group consisted of 133 people aged 12 years and older who switched to once-weekly ALTUVIIIO prophylaxis from prior prophylaxis. This group included 1 female participant. Efficacy of prophylaxis was evaluated in 128 of these patients.

The primary outcome showed a mean of <1 (0.7) bleeds per year (the median ABR was 0). Here’s a look at how the study measured bleed rates:

  • Median ABR was the middle number of all ABRs, when ABRs were ordered from least to greatest
  • Mean ABR was the average number based on everyone’s ABRs

In the pediatric study, routine prophylaxis with ALTUVIIIO resulted in a mean ABR of 0.5 and a median ABR of 0.

It’s also worth noting that 78 of the people in Group 1 participated in a separate study to measure their ABRs on their prior prophylaxis. These 78 people went from 3 bleeds to less than 1 bleed a year (mean ABR 0.7). That’s a powerful reduction of 77% in yearly bleeds!

And, over the 52 weeks on ALTUVIIIO prophylaxis, 64% of people had 0 bleeds.

Group 2

People in this group (26 participants) switched from prior on-demand therapy to ALTUVIIIO on demand for 26 weeks, and then to ALTUVIIIO prophylaxis for another 26 weeks.

This group also saw striking results. On average, people who switched from ALTUVIIIO on demand to ALTUVIIIO prophylaxis went from 21 bleeds to less than 1 bleed a year (mean ABR 0.7). That’s a 97% mean reduction in yearly bleeds.

And over the 26 weeks on ALTUVIIIO prophylaxis, 77% of people had 0 bleeds.

Both groups showed significant improvement in bleed protection with ALTUVIIIO prophylaxis.

Data based on treated bleeds.

  1. CONFIDENCE THAT YOUR JOINTS ARE PROTECTED

The XTEND-1 study also examined target joint bleeds. When evaluating joint results at 52 weeks in the 128 people who participated in the XTEND-1 study, 72% of people had 0 joint bleeds on prophylaxis after switching to ALTUVIIIO. 100% of target joints were resolved.

Target joints:

  • Are 3 or more spontaneous bleeds in a major joint within a period of 6 consecutive months
  • Were considered resolved if 2 or fewer bleeds occurred in the target joint within 12 months

‡Data based on treated bleeds.

  1. THE FEWEST WEEKLY INFUSIONS AMONG FACTOR VIII PROPHYLAXIS TREATMENTS

While most people with hemophilia grow accustomed to infusing, fewer infusions are generally preferred. In studies, ALTUVIIIO clearly outlasted other Factor VIII replacement therapies, meaning ALTUVIIIO takes longer to be reduced by half in the body and therefore lasts for a longer period.

So instead of needing up to 4 infusions a week with other treatments, patients on ALTUVIIIO infused only once per week.

ALTUVIIIO offers the fewest weekly infusions among Factor VIII prophylaxis treatments.

§This is information from a study in 13 previously treated adults with severe hemophilia A that had the goal of comparing how long ALTUVIIIO, Adynovate® [Antihemophilic Factor (Recombinant), PEGylated], and Advate®[Antihemophilic Factor (Recombinant)] stayed in the body after 1 dose. Half-life was 43 hours for ALTUVIIIO, 15 hours for Adynovate, and 11 hours for Advate.
||Doses and dosing intervals may be adjusted.
Adynovate and Advate are registered trademarks of Baxalta Incorporated, a Takeda company.

Hear from other people living with hemophilia A who have made the switch.

Now that you’ve learned about how ALTUVIIIO can keep factor levels higher for longer and protect you from bleeds, you may be considering a conversation with your doctor about switching up your treatment plan. Our Evaluation Guide can help. It offers a list of helpful questions to help you jump-start the conversation. You can also connect with your local Sanofi Community Relations and Education (CoRe) Manager, who can share additional resources and provide education.

INDICATION

ALTUVIIIO® [antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl] is an injectable medicine that is used to control and reduce the number of bleeding episodes in people with hemophilia A (congenital Factor VIII deficiency).

Your healthcare provider may give you ALTUVIIIO when you have surgery.

IMPORTANT SAFETY INFORMATION

What is the most important information I need to know about ALTUVIIIO?

Do not attempt to give yourself an injection unless you have been taught how by your healthcare provider or hemophilia center. You must carefully follow your healthcare provider’s instructions regarding the dose and schedule for injecting ALTUVIIIO so that your treatment will work best for you.

Who should not use ALTUVIIIO?

You should not use ALTUVIIIO if you have had an allergic reaction to it in the past.

What should I tell my healthcare provider before using ALTUVIIIO?

Tell your healthcare provider if you have had any medical problems, take any medications, including prescription and non-prescription medicines, supplements, or herbal medicines, are breastfeeding, or are pregnant or planning to become pregnant.

What are the possible side effects of ALTUVIIIO?

You can have an allergic reaction to ALTUVIIIO. Call your healthcare provider or emergency department right away if you have any of the following symptoms: difficulty breathing, chest tightness, swelling of the face, rash, or hives.

Your body can also make antibodies called “inhibitors” against ALTUVIIIO. This can stop ALTUVIIIO from working properly. Your healthcare provider may give you blood tests to check for inhibitors.

The common side effects of ALTUVIIIO are headache, joint pain, and back pain.

These are not the only possible side effects of ALTUVIIIO. Tell your healthcare provider about any side effect that bothers you or does not go away.

Please see full Prescribing Information.

sanofi

©2024 Genzyme Corporation. All rights reserved.
ALTUVIIIO and Sanofi are registered trademarks of Sanofi or an affiliate.
MAT-US-2401281-v1.0-03/2024

HEMGENIX®, etranacogene dezaparvovec-drlb, shows long-term durability, safety, and greater bleed protection versus factor IX prophylaxis at 3 years post-treatment

This is a paid public announcement from CSL Behring and does not constitute an endorsement of products or services. When you click on the links in this blog entry, you will be directed to the CSL Behring website. LA Kelley Communications always advises you to be a savvy consumer when contacting any company; do not reveal identifying information against your will

Ongoing studies offer years of durability data
The clinical trials for HEMGENIX—the first-ever gene therapy for hemophilia B approved by the FDA—are set up so that those who have received HEMGENIX are monitored on an ongoing basis. Data has been published annually and have supported the consistent safety and efficacy of HEMGENIX. Studies for HEMGENIX began in 2018 with a phase 2b trial of 3 people with 5 years of data collected. The HOPE-B phase 3 trial began in 2020 with 54 people to evaluate the safety and efficacy of treatment. The FDA approved the treatment in 2022. HEMGENIX has been studied for over 5 years, with data continuing to be collected.

Clinical Trial Durations

In December 2023, CSL Behring released the three-year results from the phase 3 trial for HEMGENIX. In the ongoing HOPE-B study, results at 3 years confirmed the durability and safety of treatment with HEMGENIX following a one-time infusion in people living with hemophilia B, and will be studied up to 5 years.

HEMGENIX—a groundbreaking option
According to Dr. Steven Pipe, Professor of Pediatrics and Pathology at the University of Michigan and principal investigator of the HOPE-B pivotal trial:

“The long-term follow-up data from the HOPE-B study reinforces that a one-time treatment with HEMGENIX can produce elevated and sustained factor IX levels and reduce the rate of annual bleeds for years in people living with hemophilia B. Most importantly, the data show that nearly all the Phase III trial participants three years post-treatment with HEMGENIX have remained free from the need for regular prophylactic infusions, which is groundbreaking for the hemophilia B community.”

Are you ready for bleed protection that lasts for years instead of weeks? Talk to your doctor about the first-ever treatment option that offers your body the ability to make its own factor IX, and whose durability and safety has been confirmed for years.

IMPORTANT SAFETY INFORMATION

What is HEMGENIX?
HEMGENIX®, etranacogene dezaparvovec-drlb, is a one-time gene therapy for the treatment of
adults with hemophilia B who:

    • Currently use Factor IX prophylaxis therapy, or

    • Have current or historical life-threatening bleeding, or

    • Have repeated, serious spontaneous bleeding episodes.

HEMGENIX is administered as a single intravenous infusion and can be administered only once.

What medical testing can I expect to be given before and after administration of HEMGENIX?
To determine your eligibility to receive HEMGENIX, you will be tested for Factor IX inhibitors. If this test result is positive, a retest will be performed 2 weeks later. If both tests are positive for Factor IX inhibitors, your doctor will not administer HEMGENIX to you. If, after administration of HEMGENIX, increased Factor IX activity is not achieved, or bleeding is not controlled, a post-dose test for Factor IX inhibitors will be performed.

HEMGENIX may lead to elevations of liver enzymes in the blood; therefore, ultrasound and other testing will be performed to check on liver health before HEMGENIX can be administered. Following administration of HEMGENIX, your doctor will monitor your liver enzyme levels weekly for at least 3 months. If you have preexisting risk factors for liver cancer, regular liver health testing will continue for 5 years post-administration. Treatment for elevated liver enzymes could include corticosteroids.

What were the most common side effects of HEMGENIX in clinical trials?
In clinical trials for HEMGENIX, the most common side effects reported in more than 5% of patients were liver enzyme elevations, headache, elevated levels of a certain blood enzyme, flu-like symptoms, infusion-related reactions, fatigue, nausea, and feeling unwell. These are not the only side effects possible. Tell your healthcare provider about any side effect you may experience.

What should I watch for during infusion with HEMGENIX?
Your doctor will monitor you for infusion-related reactions during administration of HEMGENIX, as well as for at least 3 hours after the infusion is complete. Symptoms may include chest lightness, headaches, abdominal pain, lightheadedness, flu-like symptoms, shivering, flushing, rash, and elevated blood pressure. If an infusion-related reaction occurs, the doctor may slow or stop the HEMGENIX infusion, resuming at a lower infusion rate once symptoms resolve.

What should I avoid after receiving HEMGENIX?
Small amounts of HEMGENIX may be present in your blood, semen, and other excreted/secreted materials, and it is not known how long this continues. You should not donate blood, organs, tissues, or cells for transplantation after receiving HEMGENIX.

Please see full prescribing information for HEMGENIX.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.
You can also report side effects to CSL Behring’s Pharmacovigilance Department at 1-866-915-6958.

HEMGENIX is manufactured by uniQure Inc. and distributed by CSL Behring LLC.
HEMGENIX® is a registered trademark of CSL Behring LLC.
©2024 CSL Behring LLC 1020 First Avenue, PO Box 61501, King of Prussia, PA 19406-0901 USA
www.CSLBehring.com USA-HGX-0611-FEB24

The differences between gene therapies for hemophilia A and hemophilia B

This is a paid public announcement from CSL Behring and does not constitute an endorsement of products or services. When you click on the links in this blog entry, you will be directed to the CSL Behring website. LA Kelley Communications always advises you to be a savvy consumer when contacting any company; do not reveal identifying information against your will.

Hemophilia is a genetic condition
Both hemophilia A and B are caused by mutations in the gene for blood clotting factor. Hemophilia A is caused by a mutation in the gene that creates factor VIII (FVIII) and hemophilia B is caused by a mutation in the gene that creates factor IX (FIX). Both the F8 and F9 genes are located on the X chromosome at different points.

Low factor levels lead to the inability of blood to clot, resulting in numerous physical and lifestyle burdens, including unexpected breakthrough bleeds and other chronic health problems. Over half the people with hemophilia A or B have factor levels less than 1% of normal.

Gene therapies for hemophilia A and B target different genes
Gene therapy is a long-term treatment option for people with hemophilia that offers extended bleed protection, which could eliminate the need for prophylaxis. Gene therapy uses an innovative approach that redefines treatment by either introducing a functioning gene into the body, or turning off or changing the gene that is causing the condition. Current gene therapies approved for hemophilia introduce a new, fully functioning gene into the body. The mutations causing hemophilia A and B have been characterized in thousands of people, and it is clear from the large number of mutations that the molecular basis of the condition is extremely diverse.

There are differences between gene therapies for hemophilia A and B
All gene therapy for hemophilia targets the liver. However, since there are differences in how the body produces FVIII and FIX, there are also fundamental differences in how gene therapy works in the liver.

For people with hemophilia B, gene therapy targets liver cells, known as hepatocytes, where factor IX proteins are naturally made. By delivering a functional F9 gene straight to the liver, it enables a person to start creating their own factor IX proteins that are missing or not working and causing the disorder.

In hemophilia A, a functional F8 gene is delivered to the liver, allowing it to start creating the missing or nonworking factor VIII proteins that cause the disorder. However, the way gene therapy for hemophilia A works is slightly different, since FVIII is produced by different liver cells and tissues than those that produce FIX. The F8 gene is larger and structurally complex, which creates additional challenges.

How gene therapy works
Working genes are usually delivered into the cells of the body by inserting them into an inactive viral shell, known as the vector.

Vectors being used in research are commonly made from adeno-associated viruses (AAVs). The AAV, naturally existing in the world at large, is deactivated, eliminating its ability to cause any illness while it performs its new task to deliver a therapy. In AAV-based gene therapy or gene transfer, a working gene is inserted into an AAV vector. An AAV vector protects and delivers the new gene to its destination through a one-time infusion. Current gene therapies for hemophilia A and B use different AAV vectors to deliver that new gene.

The size and simplicity of the F9 gene made it a promising target for gene therapy
Hemophilia B has long been a promising target for gene therapy because it is caused by a single gene mutation, which is both small in size and structurally simpler in comparison to hemophilia A.

In 2022, HEMGENIX®, etranacogene dezaparvovec-drlb, was approved by the FDA as the first and only gene therapy for hemophilia B. A one-time dose of HEMGENIX has been shown to offer elevated factor IX levels for years, with 37% average factor IX activity sustained at 2 years. HEMGENIX also offers greater bleed protection than prophylaxis. In a clinical trial, annualized bleed rate (ABR) for all bleeds decreased by 54% from an average of 4.1 for patients on prophylaxis during the lead-in period to 1.9 in months 7–18 after treatment. And 94% of, or 51 out of 54, people remained entirely free of continuous routine factor IX prophylaxis.

Hemophilia A has been a more challenging target for gene therapy

Due to constraints with AAV vectors, hemophilia A proved to be a challenging target for gene therapy. However, that changed recently, when the first gene therapy for hemophilia A was approved by the FDA. Administered as a single dose, gene therapy for hemophilia A has been shown to increase blood levels of factor VIII and reduce the risk of uncontrolled bleeding vs prophylaxis.

With gene therapies being approved for both hemophilia A and B, the future treatment landscape has irrevocably changed for anyone managing the condition.

IMPORTANT SAFETY INFORMATION

What is HEMGENIX?

HEMGENIX®, etranacogene dezaparvovec-drlb, is a one-time gene therapy for the treatment of adults with hemophilia B who:

  • Currently use Factor IX prophylaxis therapy, or
  • Have current or historical life-threatening bleeding, or
  • Have repeated, serious spontaneous bleeding episodes.

HEMGENIX is administered as a single intravenous infusion and can be administered only once.

What medical testing can I expect to be given before and after administration of HEMGENIX?

To determine your eligibility to receive HEMGENIX, you will be tested for Factor IX inhibitors. If this test result is positive, a retest will be performed 2 weeks later. If both tests are positive for Factor IX inhibitors, your doctor will not administer HEMGENIX to you. If, after administration of HEMGENIX, increased Factor IX activity is not achieved, or bleeding is not controlled, a post-dose test for Factor IX inhibitors will be performed.

HEMGENIX may lead to elevations of liver enzymes in the blood; therefore, ultrasound and other testing will be performed to check on liver health before HEMGENIX can be administered. Following administration of HEMGENIX, your doctor will monitor your liver enzyme levels weekly for at least 3 months. If you have preexisting risk factors for liver cancer, regular liver health testing will continue for 5 years post-administration. Treatment for elevated liver enzymes could include corticosteroids.

What were the most common side effects of HEMGENIX in clinical trials?

In clinical trials for HEMGENIX, the most common side effects reported in more than 5% of patients were liver enzyme elevations, headache, elevated levels of a certain blood enzyme, flu-like symptoms, infusion-related reactions, fatigue, nausea, and feeling unwell. These are not the only side effects possible. Tell your healthcare provider about any side effect you may experience.

What should I watch for during infusion with HEMGENIX?

Your doctor will monitor you for infusion-related reactions during administration of HEMGENIX, as well as for at least 3 hours after the infusion is complete. Symptoms may include chest tightness, headaches, abdominal pain, lightheadedness, flu-like symptoms, shivering, flushing, rash, and elevated blood pressure. If an infusion-related reaction occurs, the doctor may slow or stop the HEMGENIX infusion, resuming at a lower infusion rate once symptoms resolve.

What should I avoid after receiving HEMGENIX?

Small amounts of HEMGENIX may be present in your blood, semen, and other excreted/secreted materials, and it is not known how long this continues. You should not donate blood, organs, tissues, or cells for transplantation after receiving HEMGENIX.

Please see full prescribing information for HEMGENIX.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch , or call 1-800-FDA-1088.

You can also report side effects to CSL Behring’s Pharmacovigilance Department at 1-866-915-6958.

HEMGENIX is manufactured by uniQure Inc. and distributed by CSL Behring LLC.

HEMGENIX® is a registered trademark of CSL Behring LLC.

©2023 CSL Behring LLC 1020 First Avenue, PO Box 61501, King of Prussia, PA 19406-0901 USA

www.CSLBehring.com   USA-HGX-0466-NOV23

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