FDA Approves Octapharma’s NUWIQ To Treat Hemophilia A

by PPN Staff 

The FDA has approved Octapharma’s NUWIQ, antihemophilic factor (recombinant), an IV therapy for adults and children living with hemophilia A. The approval includes on-demand treatment and control of bleeding episodes, routine prophylaxis to reduce the frequency of bleeding episodes and perioperative management of bleeding.

NUWIQ is the first B-domain–deleted recombinant factor VIII (FVIII) derived from a human cell line, not chemically modified or fused with another protein, designed for the treatment of patients with hemophilia A, congenital FVIII deficiency.

Up to 16,000 individuals in the United States have hemophilia A. Although there are already therapies for hemophilia A, significant challenges remain, including development of inhibitors and the need for multiple infusions on a prophylactic basis, the company said.

The initial global clinical study program for NUWIQ commenced with a pharmacokinetic (PK) evaluation in an open-label, multicenter clinical trial of 22 previously treated patients (PTPs). These patients consisted of 20 adults and two adolescents. In this study, NUWIQ demonstrated a mean half-life of 17.1 hours using a one-stage clotting assay in adults. NUWIQ was also evaluated in children using a one-stage clotting assay with a mean half-life of 11.9 hours for ages 2 to 5 years and a mean half-life of 13.1 hours for ages 6 to 12 years. These PK results for mean half-life were longer than earlier generations of recombinant FVIII products currently available in the United States.

The second set of global clinical studies for NUWIQ also evaluated overall efficacy and tolerability in three prospective, open-label clinical studies in PTPs with severe hemophilia A. From all clinical studies, 135 patients were treated with NUWIQ, including 74 adults, three adolescents between ages 12 and 17 years and 58 pediatric patients between ages 2 and 11 years. All these patients were treated with a total of 16,134 infusions over 15,950 exposure days using NUWIQ.

In a study of 32 adults, overall prophylactic efficacy of NUWIQ for spontaneous bleeds was rated as excellent or good in 92% of patients. In a study of 59 children, prophylactic efficacy for spontaneous bleeds was rated as excellent or good in 97% of patients. The mean annualized bleeding rates (ABR) for spontaneous bleeds during prophylaxis were approximately 1.5 in children and 1.2 in adults. For hemophilia A patients receiving NUWIQ prophylaxis compared with on-demand treatment, the ABR was reduced 96% for adults and 93% for children.

Treatment of breakthrough bleeds during NUWIQ prophylaxis was rated as excellent or good in all of 30 (100%) bleeds in adults and 89 of 108 bleeds (82%) in children. For on-demand treatment with NUWIQ in 20 adults and two adolescents, efficacy for the treatment of bleeds was excellent or good in 931 of 986 bleeds (94%). Overall efficacy in surgical prophylaxis was rated excellent or good in 32 of 33 procedures (97%) using NUWIQ.

In all clinical studies, NUWIQ had a total of seven reported adverse events. Each of these adverse events occurred one time with a rate of 0.7% across all 135 patients. These events were parathesia, headache, injection site inflammation, injection site pain, back pain, vertigo and dry mouth.

Octapharma USA will offer hemophilia A patients educational and support services in connection with the introduction of NUWIQ, which should be available by early 2016.

NUWIQ is not indicated for the treatment of vonWillebrand disease.

“We are pleased that the treatment options for adults and children with hemophilia A continue to advance with ever more innovative therapies being approved for the U.S.,”  said Val Bias, CEO of the National Hemophilia Foundation. “The continued commitment to develop life-enhancing products for the bleeding-disorders community is absolutely vital. Empowering patients and providers with treatment options, as well as education and support programs, is extremely important to people living with hemophilia A.”

—From company press materials

A Hope For Hemophilia Patients

 For the first time, chromosomal defects responsible for hemophilia have been corrected in patient-specific iPSCs using CRISPR-Cas9 nucleases. Asian Scientist Newsroom | August 4, 2015 | In the Lab

                    

AsianScientist (Aug. 4, 2015) - Sufferers of hemophilia live in a perpetual state of stress and anxiety: their joints wear down prematurely and they have bleeding episodes that feel like they will never end. Their bodies lack the ability to make the clotting factor responsible for the coagulation of blood so any cut or bruise can turn into an emergency without immediate treatment.

Hemophilia A occurs in about 1 in 5,000 male births and almost half of severe cases are caused by identified chromosomal inversions. In a chromosomal inversion, the order of the base pairs on the chromosome are reversed so the gene doesn’t express properly and the sufferer lacks the blood coagulation factor VIII (F8) gene, which causes blood to clot in healthy people.

A Korean team led by director of the Center for Genome Engineering Kim Jin-Soo, Institute for Basic Science (IBS) and Professor Kim Dong-Wook at Yonsei University has experimented with hemophilia A-derived induced pluripotent stem cells (iPSCs) and hemophiliac mice and found a way to correct this inversion and reverse the clotting factor deficiency that causes hemophilia A.

This was the first time that iPSCs—which possess the ability to change into any cell type in the body—have been used in such a procedure. The researchers first collected urinary cells from patients with chromosomal inversions causing haemophilia, transforming them into iPSC cells. Then, they used CRISPR-Cas9 nucleases (Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR associated protein 9) to flip the F8 gene around, allowing it to be read correctly.

The corrected-iPSCs were then induced to differentiate into mature endothelial cells which expressed the F8 gene in the correct orientation. To verify that the process worked, the endothelial cells with the inversion-corrected genes were transplanted into F8 deficient mice (mice with hemophilia A) and the mice started producing the F8 clotting factor on their own, which essentially cured them of hemophilia A.

        “We used CRISPR RGENs [RNA-guided engineered nucleases] to repair two recurrent, large chromosomal inversions responsible for almost half of all severe hemophilia A cases,” Kim Jin-Soo said.

        “To the best of our knowledge, this report is the first demonstration that chromosomal inversions or other large rearrangements can be corrected using RGENs or any other programmable nuclease in patient iPSCs,” Kim Dong-Wook added.

Importantly, the studied showed no evidence of off-target mutations resulting from the procedure, suggesting that it was only the desired parts of genome were changed.

These findings open the door for further testing and if the results are anything like the mice trials, the future of this treatment looks promising.

The article can be found at: Park et al. (2015) Functional Correction of Large Factor VIII Gene Chromosomal Inversions in Hemophilia A Patient-Derived iPSCs Using CRISPR-Cas9

Source: Institute for Basic Science; Photo: Shutterstock. Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

https://www.facebook.com/Hemophilia-Awareness-446712415406740/timeline/?ref=bookmarks 

Roche hemophilia drug wins fast-track FDA designation

The logo of Swiss pharmaceutical company Roche is seen at a plant in the central Swiss village of Rotkreuz in this November 6, 2013 file photo.

Reuters/Arnd Wiegmann

Roche said on Friday it had won breakthrough therapy designation from the U.S. Food and Drug Administration for an experimental hemophilia medicine, aiming for a piece of the $11 billion hemophilia drug market.

The Swiss drugmaker said its U.S.-based Genentech unit's ACE910 secured the fast-track designation as the company prepares separate Phase III trials in 2015 and 2016, the first in patients with hemophilia A with factor VIII inhibitors and the second for patients without inhibitors.

It represents a threat to more traditional treatments from Novo Nordisk and Baxalta, the target of a $30 billion takeover attempt by Shire.

Hemophilia A is a rare genetic disorder that prevents blood clotting. Patients receive lifesaving infusions of clotting factors, but development of inhibitors in many of those being treated interferes with efforts to control their bleeding.

With the market for hemophilia medications expected to grow to $11 billion next year, Roche's ACE910 drug is closely watched because it could change the way the disease is treated.

"FDA has granted breakthrough therapy designation for ACE910, recognizing an unmet need for patients with inhibitors and the promise of these early data," Sandra Hornung, Roche's chief medical officer, said in a statement.

Last year, Roche said early data indicated encouraging reduction in bleeding rates in all patients.

In 2012, U.S. regulatory changes created the breakthrough therapy designation, allowing the FDA to expedite development and review of drugs whose preliminary clinical evidence indicates substantial improvement over existing therapies.

(Reporting by John Miller. Editing by Jane Merriman)

CDC Findings Suggest Hemophilia Carriers Vulnerable to Joint Damage

In a newly highlighted study, the US Centers for Disease Control and Prevention (CDC) concluded that hemophilia carriers showed evidence of joint abnormalities as early as the pre-teen years regardless of the severity of bleeding symptoms. Results of the study were first published in “Females with FVIII and FIX Deficiency have Reduced Joint Range of Motion,” in August 2014 in the American Journal of Hematology. The lead author was Robert Sidonio, MD, MS, Department of Pediatrics, Division of Hematology/Oncology, Vanderbilt University Medical Center in Nashville, TN.

To learn whether hemophilia carriers reported joint bleeding and showed physical signs of joint damage or destruction, CDC looked at joint abnormalities among 451 women presumed to be hemophilia carriers aged 2-69 years. The women were enrolled in a national public health tracking project called the Universal Data Collection (UDC) system. The UDC was created in 1998 by the CDC, in cooperation with the federally funded hemophilia treatment center (HTC) network, to collect vital health information on individuals with bleeding disorders in the US.

Data for the study were gathered by either an HTC physical therapist or other trained healthcare provider, who collected information on specific participant characteristics, such as race/ethnicity, income and educational level (demographic information), as well as information on bleeding and infectious disease history, and range of movement measurements in five joints (right and left shoulders, elbows, hips, knees and ankles).

CDC’s most prominent findings were:

• The proportion of female hemophilia carriers reporting at least one joint bleed in the last six months increased as the severity of hemophilia worsened
• Approximately one in seven females with mild hemophilia reported at least one joint bleed in the last six months. Mild hemophilia means they have 6% to 40% of normal clotting ability.
• Approximately one in three females with moderate hemophilia reported at least one joint bleed in the last six months. Moderate hemophilia means they have 1% to 5% of normal clotting ability.
• Approximately half of females with severe hemophilia reported at least one joint bleed in the last six months. Severe hemophilia means they have less than 1% of normal clotting ability.

Hemophilia carriers showed signs of joint abnormalities as reflected by reduced joint range of movement, which worsened with increasing levels of severity of hemophilia.

These findings suggest that joint bleeding might be occurring even before a carrier’s adolescent years. Sidonio and his co-investigators also acknowledge that this research is preliminary and that the next step is to document joint disease with X-rays and other tools.

 Source: CDC release dated March 26, 2015

26 Things People With Hemophilia and Bleeding Disorders Wish You Understood

Melissa McGlensey

Hemophilia is a rare condition where a person’s blood has a reduced ability to clot. About 400,000 people worldwide are living with hemophilia, and 400 babies are born with it each year, according to the Hemophilia Federation of America.

Perhaps because they are rare, hemophilia and bleeding disorders are often misunderstood conditions. With that in mind, The Mighty worked with two organizations, the Hemophilia Federation of America and Stop The Bleeding, to find out what people with the condition wish the world could understand.

This is what they had to say:

1. “Bleeding disorders are confounding and annoying when they act up. You can have months of no trouble, and then suddenly look as if you’re trying to avoid every outing, get together and birthday party… But I promise, it’s not personal.” — Carri Nease

2.“Hemophilia and incest are not related in any way… Also, we won’t bleed to death from a paper cut.” — Jeff Johnson

3. “We know our disease and conditions better than the average doctor does.” — Karen Guertin

4. “It’s more common than you think.” — Deana J Woods

5. “If my son falls off a tree, he will need treatment… but the most important thing is that he still gets to climb trees.” — Jennifer Empson

6. “Although hemophilia is often known as the ‘royal disease,’ it doesn’t mean everyone living with it is directly related to royalty.” — Rich Pezzillo

7. “Many of us in the community are willing to discuss our condition, and it does not prevent us from contributing to our communities.” — Donald Robert Fox

8. “It’s not only a male disease. I am a woman who is affected by the condition, along with two sons and a daughter.” — Yashica Washington

 

9. “As a mom, I’m trying to let my baby be a ‘normal,’ active 2-year-old. However, if I seem to be on edge, it’s because every time he runs, jumps, falls or hits something, I get that gut-wrenching feeling — the feeling right before a car wreck.” — Brandi Alsip

10. “I love the question, ‘You still have that?'” —  David Melendez

11. “Our kids have bruises because they have a chronic disorder and not because they’re being beaten.” — William Wilson

12. “No, your child cannot ‘catch it’ from my son.” — Gina Morris

13. “Just because you don’t see it doesn’t mean it’s not happening. And, it can be painful.” — Misty King Woodhall

14. “It’s different than necrophilia. (True story — I actually had to clarify this to a poor soul.)” — Rachel Miller Kroouze

15. “No, my boys won’t grow out of it.” — Theresa Laureen

16. “I don’t fake my injuries nor do I milk the fact that I’m hurt. I am as normal as the next person and only wish to be treated as such… I do not want pity.” — Justin Wallace

17. “We have some of the best people in our community. We can do anything together.” — Luke Vannicola

18. “You have to be prepared for an emergency at all times.” — Katie Hoagberg Masog

19. “My son doesn’t need to be bubblewrapped nor treated differently than my other son… don’t be scared.” — Samantha Francesca Costa

20. “That the impact of a bleeding disorder is so much more than the disorder itself and its physical complications. The impact is also emotional, psychological, educational, financial and relational.” — Rebecca Nastasia

21. “It is hard to live with, and you cannot just take a pill to make it go away.” — Theresa Schuman

22. “Having hemophilia does not automatically prevent you from being active. It’s actually good for hemophilia patients to be active. Being active gains muscles, which protects joints, which helps [prevent] bleeds.” — Christy Reyes

23. “I’ve lived with ‘significant’ pain most of my life, and I’ve learned to manage it. Having a bleeding disorder doesn’t weaken me, it toughens me.” — Patrick James Lynch

24. “Hemophilia isn’t being in a wheelchair, but it’s also not being immune to wheelchairs. It’s a complicated disorder that can randomly determine what life is like. One week can be spent resting in bed and using wheelchairs. Another can be running around playing soccer. I wish people understood that because it’s difficult to explain to strangers in chance encounters.” — Mark Kenny 

25. “It may have conquered my body but it shall not have my soul or my mind. Those remain mine.” — Marcus Lamarr Smith II

What Should You Know About Blood Disorders in Women?

While bleeding and clotting disorders affect men and women, these conditions pose unique problems for women because of the impact the disorders can have on their reproductive health and quality of life. Current data estimate that as many as 1% of women in the United States may have a bleeding disorder and many are unaware of their condition.

Women and Bleeding Disorders: Living with von Willebrand Disease

Meet three women and hear about their experiences living with von Willebrand Disease (VWD). Learn about the signs and symptoms of VWD and why it’s important to seek help with any questions or concerns about abnormal bleeding.

Watch the video »

 

The most common bleeding disorder affecting women is von Willebrand disease (VWD), which results from a deficiency or defect in the body’s ability to produce a certain protein that helps blood clot. Although VWD occurs in men and women equally, women are more likely to notice the symptoms because of heavy or abnormal bleeding during their menstrual periods and after childbirth. VWD and other blood disorders may also cause women to experience recurrent fetal loss, heavy bleeding during dental procedures, frequent nosebleeds, and heavy bleeding during or after surgery.

Women with heavy menstrual bleeding (menorrhagia) or VWD are at increased risk for anemia, pain during menstruation, hospitalizations, blood transfusions, limitations in daily activities, time lost from work or school, and a reduced quality of life.

In addition to VWD, other rare bleeding disorders and more common platelet function disorders may also be responsible for bleeding symptoms in women.

Although there are no cures for bleeding disorders, treatment is available to control symptoms and help women avoid complications and invasive procedures.