Hemophilia B

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

Gene therapy for hemophilia B offers long-term bleed protection with a one-time infusion

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.

The current standard of care for moderate to severe hemophilia B, factor IX prophylactic therapy, does offer bleed protection. However, it requires lifelong, routine infusions to maintain protective factor levels, and those who regularly infuse factor IX replacement products can still experience breakthrough bleeds, leading to joint damage, pain, and reduced quality of life. There is a need for a treatment option that offers consistent bleed protection with a one-time infusion that lasts years instead of weeks.

After years of scientific research and clinical studies, that option is here—HEMGENIX® (etranacogene dezaparvovec-drlb), the first and only gene therapy for hemophilia B.*

Hemophilia B is an appropriate target for treatment with gene therapy

Hemophilia B is caused by a mutation of a single gene—the F9 gene. Approaches using gene therapy to treat inherited conditions stemming from a single genetic mutation, including hemophilia B, have predominantly focused on the delivery of a working, or functional, gene using a viral vector.

Hemophilia B is an appropriate target for treatment with gene therapy because it is caused by a mutation of a single gene, the F9 gene, which is small enough that it can be packaged into an adeno-associated viral (AAV) vector.

How HEMGENIX gene therapy for hemophilia B works

HEMGENIX uses a gene therapy approach called gene transfer. Gene transfer therapy for hemophilia B starts by developing a package of genetic instructions—the functional, or working, gene. Then AAV vectors are created, which will eventually enter targeted liver cells. The package of genetic instructions is loaded into an AAV vector shell, acting as a delivery truck. Through a single IV infusion, the delivery truck heads toward the liver with its package.

Once delivered into the liver cells, the package of instructions is unloaded, enabling the liver to start generating factor IX, with the goal of allowing a person to produce their own elevated and protective levels of factor IX. After delivering its package, the AAV vector shell is broken down and eliminated. However, the genetic instructions remain to continue producing factor IX.

Built on science you can trust

Gene therapy is built on decades of clinical research. The first patients received gene therapy in 1970, and there are more than 250 AAV-based clinical trials currently underway across a variety of conditions. So not only is gene therapy with HEMGENIX EMHa great fit for hemophilia B, it’s based on years of scientific research.

Interested in learning more about the science behind HEMGENIX, a one-time infusion that offers years of consistent bleed protection? Explore all that gene therapy might offer for people with hemophilia B today!

*HEMGENIX was studied in a clinical trial of 54 male adults with moderately severe or severe hemophilia B. All people in the trial were taking factor IX prophy to treat their hemophilia B and were observed for at least 6 months on prophy before receiving HEMGENIX.

†AAV5, adeno-associated viral vector serotype 5.

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 [LINK TO: https://labeling.cslbehring.com/PI/US/Hemgenix/EN/Hemgenix-Prescribing-Information.pdf] for HEMGENIX.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch [LINK TO: 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-0464-MAY23

Gene therapy for hemophilia B offers long-term bleed protection with a one-time infusion

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.

The current standard of care for moderate to severe hemophilia B, factor IX prophylactic therapy, does offer bleed protection. However, it requires lifelong, routine infusions to maintain protective factor levels, and those who regularly infuse factor IX replacement products can still experience breakthrough bleeds, leading to joint damage, pain, and reduced quality of life. There is a need for a treatment option that offers consistent bleed protection with a one-time infusion that lasts years instead of weeks.

After years of scientific research and clinical studies, that option is here—HEMGENIX® (etranacogene dezaparvovec-drlb), the first and only gene therapy for hemophilia B.*

Hemophilia B is an appropriate target for treatment with gene therapy

Hemophilia B is caused by a mutation of a single gene—the F9 gene. Approaches using gene therapy to treat inherited conditions stemming from a single genetic mutation, including hemophilia B, have predominantly focused on the delivery of a working, or functional, gene using a viral vector.

Hemophilia B is an appropriate target for treatment with gene therapy because it is caused by a mutation of a single gene, the F9 gene, which is small enough that it can be packaged into an adeno-associated viral (AAV) vector.

How HEMGENIX gene therapy for hemophilia B works

HEMGENIX uses a gene therapy approach called gene transfer. Gene transfer therapy for hemophilia B starts by developing a package of genetic instructions—the functional, or working, gene. Then AAV vectors are created, which will eventually enter targeted liver cells. The package of genetic instructions is loaded into an AAV vector shell, acting as a delivery truck. Through a single IV infusion, the delivery truck heads toward the liver with its package.

Once delivered into the liver cells, the package of instructions is unloaded, enabling the liver to start generating factor IX, with the goal of allowing a person to produce their own elevated and protective levels of factor IX. After delivering its package, the AAV vector shell is broken down and eliminated. However, the genetic instructions remain to continue producing factor IX.

Built on science you can trust

Gene therapy is built on decades of clinical research. The first patients received gene therapy in 1970, and there are more than 250 AAV-based clinical trials currently underway across a variety of conditions. So not only is gene therapy with HEMGENIX EMHa great fit for hemophilia B, it’s based on years of scientific research.

Interested in learning more about the science behind HEMGENIX, a one-time infusion that offers years of consistent bleed protection? Explore all that gene therapy might offer for people with hemophilia B today!

*HEMGENIX was studied in a clinical trial of 54 male adults with moderately severe or severe hemophilia B. All people in the trial were taking factor IX prophy to treat their hemophilia B and were observed for at least 6 months on prophy before receiving HEMGENIX.

†AAV5, adeno-associated viral vector serotype 5.

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 [LINK TO: https://labeling.cslbehring.com/PI/US/Hemgenix/EN/Hemgenix-Prescribing-Information.pdf] for HEMGENIX.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch [LINK TO: 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-0464-MAY23

What a doll!

Our eminent researcher of all things hemophilia, Richard Atwood of North Carolina, has found a book with “paper” dolls related to hemophilia! I certainly had paper dolls growing up, and apparently, we still have them for kids these days.

Nicholas and Alexandra Paper Dolls, published in 1998, is an oversized book (9”x12”) on the family of the last Romanov Tsar, Nicholas II, whose son Alexei had hemophilia B. The book includes 11 dolls on 16 plates printed on lightweight cardboard. There are two pages of text with notes and instructions to provide historical insights and fashion commentary. Alexandra has two dolls, accompanied by six dresses, including her 1894 wedding dress and 1896 coronation dress, plus ball gowns. Nicholas has two dolls, accompanied by five uniforms. Alexei’s older sisters, Olga, Tatiana, Marie, and Anastasia all wear the same casual dresses, that may be covered by two sets of identical dresses. Alexei is dressed in a sailor suit that may be covered with a uniform. Other dolls are the mad monk Gregory Rasputin in a monk’s garb and Clementy Nagorny in a sailor suit. The book cover illustration could also be used as dolls for Nicholas, Alexandra and Alexei.

The life of Alexei is briefly summarized. Alexei was born in August of 1904. From his mother, he inherited hemophilia B that was soon evident to the family, who did not publicly reveal it. Hemophilia was a deadly disease then, with no known cure. The bleeding bouts caused pain. Gregory Rasputin is described as a healer who used hypnosis to relieve Alexei’s suffering. Rasputin is also described as a lecher, a drunkard, and a con man. Clementy Nagorny was one of two sailors who acted as Alexei’s nanny.

Alexei is correctly shown with a bent left leg, though the metal brace he wore for most of 1913 is hidden. Something not revealed in the text is that Alexei’s accident at Spalo in 1912 caused femoral neuropathy (or paralysis of femoral nerve) due of an iliacus hematoma (or an iliopsoas muscle bleed). This was the medical reason for his hip flexion and bent leg. The metal brace, not Rasputin, straightened Alexei’s left leg. The instructions printed in the book do not mention the need for a sharp cutting tool such as an X-Acto knife in order to remove the dolls and clothes from the book pages.

The author, Tom Tierney, who is an artist, has signed each of the 11 dolls. Tierny is known for his series of paper dolls for a variety of historical figures, including Queen Elizabeth II, Michelle Obama, Abraham Lincoln, Shakespeare characters, and more.

And, you can still buy this on Amazon.com!

From Mineola, NY: Dover Publications. 32 pages.

New Episodes of the Infusion Squad Take Kids with Hemophilia B on a Mission into the Bloodstream

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.

Two new episodes of the Infusion Squad are now available from Sanofi to take kids with Hemophilia B on an audio adventure through the bloodstream.

Anyone who deals with children knows that getting them to sit still for more than a few minutes can be mission impossible. This can be especially challenging for children with hemophilia B who may receive regular infusions of Factor IX therapy that helps them manage their hemophilia. 

For entertainment and education during the infusion process for children and their caregivers, Sanofi launched the audio adventure series, Infusion Squad, available as an Amazon Alexa voice skill for patients in the U.S. The now ten-episode series is designed for children aged 12 and younger but is fun for any age.

Part educational and part entertaining, each episode takes a team of “Infusionauts” and the children on a mission into the bloodstream. Along the way, children learn more about infusion and the role that factor IX plays in hemophilia B. 

The series was created based on patient research and focus groups that found it can be challenging for children to stay still during the infusion process. They also expressed the need for educational materials to help families learn about hemophilia B and infusing. 

Available in English, the Infusion Squad skill can be enabled on the Alexa app, Alexa Skills store, or on any Alexa-enabled device. Just ask Alexa to “enable Infusion Squad” and you’ll be dropped right into numerous episodes of hands-free adventure.

To learn more about the Infusion Squad or a treatment option for Hemophilia B, visit https://bit.ly/30mc6fE . You can also contact your local Sanofi Community Relations and Education Manager here.

© 2022 Genzyme Corporation. All rights reserved. Sanofi is a registered trademark of Sanofi or an affiliate. Amazon, Alexa and all related logos are trademarks of Amazon.com, Inc. or its affiliates.

MAT-US-2204695-v1.0-06/2022

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