Lifelines for Health (vol. 3): Unlocking the Plasma Portal by CHES

Summer 2014 I Volume 3

A CHES Publication

Puzzling Cases?

Achieve response with the power and stability of the FVIII/vWF Complex*

FVIII

von Willebrand

Koate ˉ ®-DVI1,2: * Ko ate ˉ ®-DVI has not been investigated • Is indicated for the treatment of classical for efficacy in the treatment of von Willebrand disease, and hence hemophilia A is not approved for such usage • Demonstrates a mean biologic half-life of 16.12 hours ** A total of 306 bleeding episodes were • Contains naturally occurring vWF* treated. 82% of the bleeding episodes • Is well-tolerated with low risk (0.7%) of adverse reactions were treated adequately with a single infusion of FVIII • Is effective in a single dose** Important Safety Information Koate ˉ ®-DVI is made from human plasma. Products made from human plasma may contain infectious agents, such as viruses, and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent that can cause disease. There is also the possibility that unknown infectious agents may be present in such products. Hepatitis B vaccination is essential for patients with hemophilia A; vaccination is recommended at birth or at the time of diagnosis. Hepatitis A vaccination is also recommended for hemophilia patients who are hepatitis A seronegative. When large or frequently repeated doses are required, patients of blood groups A, B, or AB should be monitored for signs of progressive anemia. ©2014 Kedrion Biopharma, Inc. All Rights Reserved. Printed in USA June 2014 KT-0077-00-2014

Allergic-type reactions may result from the administration of Antihemophilic Factor (Human) preparations. Reactions include tingling in the arm, ear, and face, blurred vision, headache, nausea, stomach ache, and jittery feeling. 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. Please see next page for Brief Summary of Koate ˉ ®-DVI Product Information. For Full Product Information, please visit www.koate-dviusa.com. References: 1. Koate ˉ ®-DVI [prescribing information]. 2012. 2. Powell JS, Bush M, Harrison J, Abildgaard C, Vosburgh E, Thompson AR, Hurst D. Safety and efficacy of solvent/detergent- treated antihaemophilic factor with an added 80 degrees C terminal dry heat treatment in patients with haemophilia A. Haemophilia. 2000;6(3):140-9.

Koˉate®-DVI [Antihemophilic Factor (Human)] Brief Summary: Please see Koate ˉ ®-DVI Full Prescribing Information for complete product details. Koate ˉ ®-DVI [Antihemophilic Factor (Human)] is a sterile, stable, purified, dried concentrate of human Antihemophilic Factor (AHF, Factor VIII) used to treat classical hemophilia (hemophilia A) in which there is a demonstrated deficiency of activity of the plasma clotting factor, Factor VIII. Koate-DVI ˉ contains naturally occurring von Willebrand factor, but has not been approved for the treatment of von Willebrand disease. Warnings Koate-DVI ˉ is made from human plasma. It may contain infectious agents that can cause disease, such as viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent. The risk that the product will transmit an infectious agent has been reduced by screening plasma donors for prior exposure to certain viruses, by testing for the presence of certain current virus infections, and by inactivating and/or removing certain viruses. Despite these measures, the product may carry a risk of transmitting infectious agents, including unknown infectious agents. Individuals who receive infusions of blood or plasma products may develop signs and/or symptoms of some viral infections, particularly hepatitis C. Hepatitis B vaccination is essential for patients with hemophilia and it is recommended that this be done at birth or diagnosis. Hepatitis A vaccination is also recommended for hemophilic patients who are hepatitis A seronegative. Precautions Koate-DVI ˉ is intended for the treatment of bleeding disorders arising from a deficiency in Factor VIII. This deficiency should be proven prior to administering Koate-DVI. ˉ Koate-DVI ˉ should be administered within 3 hours after reconstitution and should not be refrigerated after reconstitution. Administer only by the intravenous route, and use a filter needle prior to administering. Koate-DVI ˉ contains levels of blood group isoagglutinins, which are not clinically significant when controlling relatively minor bleeding episodes. When large or frequently repeated doses are required, patients of blood groups A, B, or AB should be monitored by means of hematocrit for signs of progressive anemia, as well as by direct Coombs’ tests. Product administration and handling of the infusion set

and needles must be done with caution. Place needles in sharps container after single use and discard all equipment including any reconstituted Koate-DVI ˉ product in accordance with biohazard procedures. Percutaneous puncture with a needle contaminated with blood can transmit infectious viruses including HIV (AIDS) and hepatitis. Obtain immediate medical attention if injury occurs. Some viruses, such as parvovirus B19 or hepatitis A, are particularly difficult to remove or inactivate at this time. Parvovirus B19 most seriously affects pregnant women and immune-compromised individuals. Symptoms of parvovirus B19 infection include fever, drowsiness, chills, and runny nose followed about 2 weeks later by a rash and joint pain. Evidence of hepatitis A may include several days to weeks of poor appetite, tiredness, and low-grade fever followed by nausea, vomiting, and pain in the belly. Dark urine and a yellowed complexion are also common symptoms. Patients should be encouraged to consult their physician if such symptoms appear. Pregnancy Category C Animal reproduction studies have not been conducted with Koate-DVI. It is also not known whether Koate-DVI ˉ can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Koate-DVI ˉ should be given to a pregnant woman only if clearly needed. Pediatric Use Koate-DVI ˉ has not been studied in pediatric patients. However, the previous formulation, Koate-HP, ˉ had been used extensively in pediatrics. Spontaneous adverse event reports with Koate-HP ˉ for pediatric use was similar to those reported for adult use. Adverse Reactions Allergic-type reactions may result from the administration of Antihemophilic Factor (Human) preparations. In clinical studies, 0.7% of infusions were associated with adverse reactions. All reactions were mild and included paraesthesia (numbness), blurred vision, headache, nausea, abdominal pain, and feeling jittery. The information provided in this brief summary should not replace a conversation with your physician. It is important to talk to your physician about treatments that are appropriate for you. For Koate ˉ ®-DVI Full Prescribing Information, please visit www.koate-dviusa.com. 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.

Integrity, Accuracy, Empathy...

CONTENTS

FEATURE 15 I Unlocking the Plasma Portal

Plasma-derived products have been sent to a far away place to be avoided and forgotten for decades now. Many of us have suffered firsthand or indirectly from the safety risks of these products at one time. But for some, recombinant isn’t enough, and the current industry’s safe practices justify what little risk remains.

COMMUNITY CHATTER

INSURANCE CORNER

5 I Inhibitor Family Camp: It’s All in the Perspective

9 I Maintaining Your Preferred Specialty Pharmacy Provider

The Zhao’s (family of four) share their personal experiences after returning to Inhibitor Family Camp this spring in Lake Hughes, CA. Each of them putting a different perspective on the weekend, proving that there’s a little something for all varieties of the family.

Health insurance is a gi-normous, ever-changing machine, and unfortunately, our insurers are behind the controls. What you can do to continue to use your preferred specialty pharmacy when your insurance company says you have to use their preferred provider.

7 I HFA Symposia Inhibitor Track: A Very Welcome Addition We asked, they heard us! HFA launches the first Inhibitor Track at their annual symposia.

BLOODLINES 21 I FDA-Approved: New Products Available The first of many new products for the bleeding disorder community make its way through the pipeline.

LIFELINES for HEALTH

Summer 2014

FUN & INSPIRATION 19 I Crossword Puzzle 20 I My Right Arm What do you do when a curve ball is thrown at you? Eleven-year-old Blake Katzman would tell you that strong determination and sheer will can help you overcome just about anything. This is his story.

CONTENTS

Letter From the Editors Welcome to the summer issue of the only newsletter dedicated to the inhibitor community! We are thrilled to continue to bring to you information that is pertinent and specific to your lives. As individuals who live with hemophilia and an inhibitor, we understand the challenges, struggles and concerns that are very different than having “just hemophilia”. Although each one of us face challenges that are individually unique, what unifies us is thatt sense of knowing each other’s battles and triumphs. We are so excited to bring you this edition of Lifelines for HealthSM that focuses on two topics that generate a lot of discussion; plasma-derived products and home health care companies. Our Feature on plasma-derived products brings up many difficult feelings and questions, but we believe it is a topic that needs to be addressed. For those of us that have failed immune tolerance induction on a recombinant product, plasmaderived products either in the form of a bleed management agent or another immune tolerance option often becomes a necessity. Many of us have had the experience of knowing, loving or losing a family member or friend affected by tainted blood products in the 1980’s. Making a decision to use plasma-derived products is a very personal one and CHES does not encourage the use of any factor product over another. Our goal is to help you to understand all of your options so you can make the best decision with your health care team.

Holdings, Inc.

Our Specialty Pharmacy is Experienced in Inhibitor Care The development of inhibitors is the most challenging problem that patients with hemophilia and their treaters face today. • We advocate on behalf of patients • We simplify access to product

• Abogamos por pacientes

• Insurance assistance

• Simplificamos acceso a productos

• Individual packaging & shipping arrangements

• Proveemos asistencia de aseguranza • Coordinación de envío y empaque personalizado • Asistencia español

www.nc-hs.com • customerservice@nc-hs.com Toll-Free: 877.616.6247 • Fax: 877.777.5717

LifeLines for HealthSM Disclaimers

In our Community Chatter section, as always we bring you news of events and programs specific to the inhibitor community written by community members. Our BloodLines section features information about four new products released into the market space for the bleeding disorder community. Our Insurance Corner section focuses on ways you may be able to keep your preferred home healthcare provider in a landscape where that choice is being taken away at a rapid pace. The Fun and Inspiration section is meant to provide the levity and triumphs we need and to celebrate as we navigate this path in our lives. As the late Maya Angelou says, “ One isn’t necessarily born with courage, but one is born with potential. Without courage we cannot practice any other virtue with consistency. We can’t be kind, true, merciful, generous or honest.” Lastly, we want to hear from you-our courageous family! What do you like, what should we include? This is YOUR newsletter! We are so happy to bring it to you. Enjoy! - Janet Brewer & Eric Lowe jbrewer@comphealthed.com l elowe@comphealthed.com

The views and opinions of our writers are not a reflection of Comprehensive Health Education ServicesTM, Inc. (CHES), or its’ sponsors. This newsletter is designed to provide a forum for community members to express their views from an open and honest platform. It is meant to provide a sharing of knowledge and experience meant to help one another. Nothing in this newsletter is meant to replace the advice of your HTC, medical professional team or insurance provider. You are always urged to seek the opinion of a healthcare professional for treatment and your specific insurance provider for information. We take your privacy very seriously. We would never disclose your personal health information without your express written consent. We would never sell nor make available our secure database to anyone. Articles and pictures may not be reproduced, published, and/or placed on websites without the express written permission of CHES. In every publication of LifeLines for HealthSM, we will provide links to other websites that are not owned or controlled by CHES or its sponsors. We cannot be responsible for privacy practices of other website owners, nor can we be responsible for the accuracy of the information provided.

It’s All in the Perspective

hey say that a picture is worth a thousand words. But what if three people were to describe that same picture? Is it still a thousand words, or is it now three-thousand? After all, we all seem to hold different viewpoints on everything from the sun to the bumps on a crocodile’s back. The Zhao family of Pennsylvania has 3 stories to share, but all about the same experience. Learn how Inhibitor Family Camp means a little something different to each of them.

Photo by Jane Cavanaugh-Smith

Inhibitor Family Camp 2014:

A Mom’s Perspective by Sha Ha

on his chest. Because he didn’t respond to the immune tolerance treatments, Ryan kept bleeding in his joints, muscle, neck, and most scary of all, his spinal cord. We were drained, helpless, Sha Ha with daughter, Lily and husband, Shuang and alone. We didn’t know what the future would hold. We were desperate to find other families we could echoed all weekend long in the mountains talk to. We learned about the Inhibitor and on the lake. We the parents, gathered at Family Camp in 2012 and decided to give evening parents’ café. There, we no longer it a try, not sure how the experience would felt lonely and helpless. There, families from turn out. We came back with full luggage: all over the country bonded together. There, a Big Stick Award for Ryan for his first self- we saw a future for our kids. infusion and a list of families Our kids may not run as fast as who rode the same roller coaster as we did and who taught us that others, but their journey through there were no hurdles we could life will be as rich as anyone else’s. not overcome. I made a photo book of this life-changing event and have “We come from the Turtle, living in the formed a habit to open it whenever I need Turtle. Go out from the Turtle, and turn the an extra dose of encouragement. world around.” (Clap! Clap! Clap!) The We have become loyal campers ever kids’ humming of the camp song brought since. This year we went to The Painted me back to the airplane ride. Our world has Turtle, a beautiful camp snuggled against indeed been turned around - by Inhibitor the mountains of Southern California. We Family Camp. The world has become smaller met new families and reunited with old because we have gotten to know families ones. The children’s cheers and laughter from other parts of the country; the world has become warmer because we no longer feel alone; the world has become brighter because we have built such strong community bonds. Sha Ha is a biochemist and a manager at Merck, focusing on vaccine research Thank you, CHES, The Painted Turtle, and and development. Her husband, Shuang Zhao, works for an intellectual property the wonderful volunteers. You have made us law firm. They have a 13-year-old son, Ryan Zhao, who has severe Hemophilia stronger. We have a mission to accomplish A with inhibitors. They also have a 7-year-old daughter, Lily. The family lives in and it is every bit POSSIBLE! Blue Bell, Pennsylvania. “We come from the mountains, living in the mountains. Go back to the mountains, and turn the world around.” (Clap! Clap! Clap!) Singing coming from the seats in front of me woke me up on a late night flight home from California. Obviously, Ryan and Lily were still having fun because of the new friends they made from the weekend. I smiled, but felt tears coming down my cheeks. Images from the past 13 years flashed back through my mind. I remembered how my world almost collapsed when my son Ryan, six months after birth, developed a huge hematoma in his right eye from a slight bump of his head on the crib. Ryan bled for more than ten days while my husband and I waited desperately for a diagnosis. To this day, the image of Ryan with a bloody eye still wakes me up at night from time to time. Ryan was eventually diagnosed with severe Hemophilia A, and later with inhibitors. In the years that followed, emergency room and operating room visits almost became a routine in our lives. I often couldn’t remember how many ports Ryan had during that time, only to be reminded by counting the scars

LIFELINES for HEALTH

Summer 2014

by Ryan Zhao

The trip to the Painted Turtle was a wonderful experience for me. The best thing about it was that I felt a sense of belonging. In normal camps, I always feel awkward, or held back because of my hemophilia. I was different from everyone else and that created a barrier between other campers and me. At the Painted Turtle, however, I was free! I could do what I really wanted to do, instead of trying to act like a “normal” person. I could talk to others about hemophilia as opposed to hiding it. Everyone there had experienced the challenges of hemophilia and an inhibitor. That brought us closer together and allowed me to make many new friends. The activities at the Painted Turtle were also amazing! They had everything from fishing to woodshop to horseback riding. There was a gym for the more active people, and a wide outdoor pavilion at arts and crafts for those who like to be indoors. I loved the woodshop and the arts and crafts center. They had such a wide variety of things to do. I could spend days there without ever getting bored! At the woodshop, my mom and I worked hard on a Pinewood Derby car. My mom had a great idea of making a painted turtle, and I turned it into a reality. We called our car

“The Painted Turtle,” feeling confident that it would be a great ride. And it sure was! At the Pinewood Derby where the whole camp gathered, each family participated in the race. Creativity and competitiveness ran high. Pun’s humorous commentary filled the room with laughter. The competition was friendly but intense. In the end, “The Painted Turtle” won! That is a moment I will treasure for the rest of my life. Finally, the trip would not have been the same without the wonderful people there at camp. The CHES organizers, camp staff and activity pals were so nice! In the woodshop, Pops was a big help. He knew how to use the woodcutting tools, and helped me shape my derby car. Pun’s puns filled my days with laughter and taught me many great life lessons too. The family pals were like family. Kelsie and K-Pod accompanied me everywhere and showed me where everything was. They were like the big sisters I always wanted to

For registration and program info on Inhibitor Family Camp, see page 8.

have. They made camp feel like a vacation home. The three days at the Painted Turtle passed too fast. As I waved good-bye to the red cabins, the warm California sun, and

Photo by Jane Cavanaugh-Smith

A Camper’s Perspective

Ryan with prized-possession derby car

the many new friends, I promised myself that, “Painted Turtle, I WILL BE BACK!”

A Sibling’s Perspective

by Lily Zhao

This past April, my family went to the Painted Turtle. We went because my brother, Ryan, has hemophilia with an inhibitor. My family and I had so much fun at the Painted Turtle. I wanted to stay there for another week! The activities were my favorite part. There was archery, boating, fishing, wood shop, arts and crafts, and horseback riding. In the evening, we also had a carnival and stage night. I liked all of the activities, but if I had to pick my three favorites, I would choose

horseback riding, the carnival, and arts and crafts. In horseback riding, we got to ride on a horse/pony and go through obstacles. The horse I rode on was named Diamond. In arts and crafts, you could make almost anything you wanted. You could even decorate a rock and put it in the “rock garden.” The carnival was so much fun. There were fun games, dancing and even prizes. Other things I liked about the Painted Turtle were the weather and the cabins. The weather was warm and breezy, perfect for a hike. The cabins were amazing! They were nice and cozy. Last but not least (which I thought was the best), was having the family pals and staff joining us. They were helpful, funny, and kind. “Pun” and “Pops” were very funny and exciting. Kelsie (our family pal) was like a big sister. We were sad she had to leave early. “Pun” told very funny jokes. For example, when I first met him he said that my mom was my older sister and that I was 29 years old. I had a very good time at the Painted Turtle. I hope next year my family will come here again!

COMMUNITY CHATTER

HFA Symposia Inhibitor Track: by Justin Levesque

nhibitors were quite honestly a topic I always assumed to be “Not my problem, next question, please!” But just three years ago, five months shy of turning twenty-six, BAM, it was my problem. And whoa, no seriously, whoa, it was the ultimate bleeder game-changer in my life, as I knew it. As a self-sufficient adult thrust into a strange and unfamiliar world, I suddenly had to become a HemoMom to myself! So first and foremost, I need to thank tremendously supportive folks like Sonji Wilkes at HFA who procured a scholarship for me to attend HFA’s Inhibitor Track and Janet Brewer for asking me to share that experience with you here. As we’ve come to expect from the Hemophilia Federation of America’s yearly Symposium, their 2014 agenda promised many educational and social opportunities for the bleeding disorders community. It’s a pleasure to report HFA was again able to deliver that promise in (mostly) sunny Tampa, Florida.

A Very Welcome Addition

This year, there was much pre-conference excitement and buzz surrounding the official announcement of a newly formed Inhibitor Track. Not your typical Inhibitor 101, not the basics you might simply Google, but an in-depth look at treatment approaches, upcoming technologies and science as it pertains to those of us who are consumed with an #inhibitorlife. Families and individuals affected by an inhibitor asked for this specialized track and HFA has clearly heard their voice by providing programming that aimed to reach all who have been (and most likely still are) in “Inhibitor World” for the long haul. Lasting nearly one full day before your typically scheduled symposium events, the Inhibitor Track set out to cover five areas of concern, presented by respected members of the bleeding disorders medical community who have had extensive experience with inhibitors. The sessions were as follows:

Out of Control: What Sends an Inhibitor into Overdrive? By Sue Geraghty, R.N.

In Out of Control, Sue presented a refresher course on some of the basics. It should be noted that Sue was very intentional in what she covered in the first presentation to create a clear foundation for her colleagues to build more complicated ideas upon. Interestingly, but not surprisingly, the best moments occurred (and continued to through the track) when members from the community asked questions. Out of Control was successful in addressing the impact (if any) that an individual’s Bethesda unit has on overall bleeding once 10bu has been surpassed and further, how to move beyond that number to focus on a care plan.

Immunology: What’s the Immune System Got to Do With It? By Christine Kempton, M.D.

Immunology was one of those sessions that nearly made me exclaim “Finally!” with a comprehensive but accessible investigation into the process of how an inhibitor, well, inhibits when factor replacements are injected into the body. From lymphocytes, to controversial risk factors, to immune-suppressant drugs; Christine didn’t hold back any information when it came to making sure consumers left with an intimate knowledge of what was actually happening in their own bodies. Overall, a most refreshing contrast to the blank stares one might receive when you repeatedly ask “But why?!” over and over again.

Justin Levesque earned a B.F.A. in Art & Art History from the University of Southern Maine. He specializes in the critical analysis of images and their impact on social norms & community expectations. He currently lives in Portland, Maine and runs his own design studio, Shop Geometry. Justin also volunteers as a camp counselor, recognizes creativity with his program Art Stars by FOLX, and now serves as Creative Director for The Hemophilia Alliance of Maine. He has hemophilia A (severe) with a high titer inhibitor.

LIFELINES for HEALTH

Summer 2014

TLC from the PT: Why Inhibitor Patients Need a Physical Therapist By Sharon Funk, P.T.

Sharon popped into Tampa for, I think, literally two hours to give her TLC from the PT presentation and then rushed away moments after to attend another event with the men participating in the AFFIRM program. I give her props for making her talk well paced and informative. Initially, TLC was reminiscent of other sessions I’ve attended about physical therapy, but she highlighted the extra importance for people with inhibitors to adopt joint strengthening and mobility exercises as much as possible. Key words being “as possible.” To my delight, Sharon was pragmatic and downright realistic about the state of the body when it comes to inhibitors. While every measure should be taken to preserve the physicality of the body, she emphasized the importance of alternatively knowing one’s limitations and to pursue fulfilling experiences in education, music, arts and creativity. If your body isn’t cooperating you might as well start working on your brain. Indeed! What’s New in Inhibitor Research? By Michael Callaghan, M.D.

Moving on, we approached the most anticipated sessions of the day, a double whammy that included a Research Update by Michael Callaghan M.D. and somewhat ominously, Racial Disparities, by Tom Howard M.D. Dr. Callaghan’s research update covered advancements in current bypassing agent dosing guidelines and the state of upcoming technologies. I

was certainly excited to learn that there were several unique developments in how treating or eradicating an inhibitor might be accomplished. The most rousing of which having to do with production of medication using rabbit milk! This had the room both curious and cotton-mouthed for several moments. Eliminating Racial Disparities in the Development & Eradication of FVIII Inhibitors using Pharmacogenomics-Based Diagnostics & Therapeutics By Tom Howard, M.D.

There’s no denying that the incident rate of inhibitor development is disproportionately higher in nonCaucasian communities. But why is that? Dr. Howard’s presentation made an attempt to acknowledge this phenomenon but unfortunately the material covered was just too technical for this non-medical audience to process, synthesize and apply to their scope of understanding the occurrence. If anything were to be taken away from the session it would be: 1) current factor replacement therapies are created using a Caucasian factor protein as the model in production of recombinant products. 2) Factor proteins found naturally in non-Caucasians individuals differ on a genetic level from Caucasians and perhaps might account for a higher incidence rate. 3) Genetic testing might provide the creation and advancement of personalized factor replacement therapies and allow for a more varied and diverse inclusion of factor proteins as they might be needed given one’s family history. I’ll say that the title of this session and its’

content were slightly incongruous to one another. I found myself wondering how this seemingly accidental version of, dare I say, institutional racism wasn’t being addressed directly and if it would really be so hard for factor manufacturers to adopt additional factor protein models into their current production methods. In terms of the future, personalized factor sounds fantastic and promising but while it’s important to keep looking forward, I can’t help but wish that someone or some entity would examine and discuss the actual racial disparity and its’ impact on our community. As the Inhibitor Track completed, I found myself in a room full of others who understood my story and I truly feel we left that place together armed with more information than we’ve ever previously received. Others have been critical that the track was private and closed to the community unaffected by an inhibitor. The inhibitor track was closed not as a way to exclude people in the community but to provide already diagnosed folks a safe environment to discuss the issues. Similar to how men aren’t allowed to participate in Blood Sisterhood or how someone in their twenties can’t attend a teen session. Hopefully this summary has provided a general overview to the track and how I perceived it. I highly encourage everyone to download the slide decks on each of the topics above located on the HFA website. http://www.hemophiliafed.org/resourcelibrary/2014-inhibitor-track-presentationsat-hfa-symposium/

COMMUNITY CHATTER

Maintaining Your Preferred Specialty Pharmacy Provider by Mark Zatyrka

ver the past ten years our bleeding disorders community has been dealing with the major issue of not having access to qualified factor providers. Many families are losing their choice of providers, or at best being frequently challenged in that choice. When a member of the bleeding disorders community finds a good HHC (home healthcare company, also known as homecare or home infusion company, specialty pharmacy, and for the sake of this article, HTCs who sell factor through its’ 340B program), they tend to grow very tight bonds and have a level of comfort and trust with their HHC. It can be invaluable to have someone who you can always call, 24/7, who knows your exact needs and preferences, your history, etc. Having a reliable HHC can ease the burdens that come with living with hemophilia and its’ complications, such as an inhibitor. It is important that when it comes to the health of your child or yourself, you know the right factor will arrive at the right place at the right time and should an emergency arise, your HHC will be there for you. This reality is all especially true for families living with an inhibitor, who may need even more specialized and personalized services. You need to be able to have access to a company who knows inhibitors inside and out. You have enough to deal with and no one has the time to explain every month what an inhibitor is, why you need so much factor, why you need multiple brands of factor, what a bypassing agent is and so on.

Accessing the Situation Before you begin to fight the battle with an insurer who won’t let you use the HHC you trust and are comfortable with, it can be helpful to know why they are making the decisions they are making. There are usually two reasons why an insurer will not allow a subscriber, who has out-of-network benefits, to use the HHC of their choice. 1. The insurer signed a “one-stop-shop” deal with one or two large pharmacies These pharmacies may not have the lowest per unit price on factor, but the insurer sees value in the pharmacies’ pricing on all the drugs across the board as well as cost savings in only having to deal with one or two pharmacy providers. 2. “Vertical Integration” This trend is one of the scariest in healthcare today. One definition states, “vertical integration is where the supply chain of a company is owned by that company.” In healthcare, vertical integration happens when the insurer owns the pharmacy benefit manager (PBM), the pharmacy, and even the hospital. For example, Xyz Insurance Company tells all their subscribers with hemophilia that they need to use Xyz Specialty Pharmacy if they want their factor paid for. This is a huge conflict of interest issue and we, the patients, are the ones who suffer. Like the above reason #1, the pharmacies have zero incentive to provide quality service. Once insurers remove your ability to bring your business elsewhere, it no longer matters if you are happy.

LIFELINES for HEALTH

Because of these two reasons, you can see why getting the insurer to make an exception for you is such a hard battle to win. We always hear that insurers are doing what they are doing to “control costs,” but when you look at the big picture, it is clear that it is much more about increasing profits than it is about controlling costs. In the past, a HHC could offer a lower per unit price for factor in efforts to work with families to keep them on their services. In the two reasons listed above, neither one cares about the per unit price. HHCs today rarely if ever set their reimbursement price. Insurers decide what they will pay and that’s what HHCs accept. In fact, most insurers will not even accept lower rates when offered. When we have a client at AHF who will need large amounts of factor, we usually contact the insurer to try to negotiate a lower rate. Surprisingly, insurers have never taken us up on it. We get the sense that they do not want to create more paperwork and exceptions that they need to keep track of. We have even offered to accept a much lower rate to help a family stay on our service and again, that offer has always been declined. These experiences prove the “per unit price” is not the insurer’s priority when choosing which HHCs their subscribers are allowed to access. Below are some tips you can try when your insurer is preventing you from choosing a new HHC or prohibiting you from staying with your current HHC. But keep in mind, the way insurers and PBMs are set up now, these battles are lost more than they are won, so the odds are stacked up against you. (But we are used to that, right!)

Summer 2014

Tip 1: Know your plan You can ask your HR department or call your insurer’s Customer Service dept. and ask for a written copy of your “Certificate of Coverage” (COC). This should be provided free of charge. This document explains the health benefits you and your dependents have under your plan. It details the services that will and will not be covered. This is a large document, usually 50-200 pages long. The 1-2 page outline of your co-pays and deductibles has some good information, but in order to really know what your rights are and how your factor is billed, you need your full COC. Every insurer is different, every plan type within the insurer is different, and every individual plan can be different. Tip 2: Be prepared If you are told a change is happening, be sure to place your monthly factor order with your current HHC prior to the deadline given to you by your insurer. You do not want to be left without factor and need to order from your insurer’s preferred provider. Not only can it take a week or more to get set up with these big PBMs, it also becomes nearly impossible to get permission to switch back to your preferred HHC once you place an order with the insurer’s preferred provider. Verifying your insurance, waiting on your physician to send over your prescription, waiting on prior authorizations and/or pre-certifications and delivery time all can take time to happen. Make sure you have adequate factor on hand for the transition.

Tip 3: Find out if your HHC is willing to fight for you? It is difficult enough to win these battles. You really need to have your HHC fight for you because this process can consume many hours. Who you need to talk to, what questions do you need to ask, and how to ask those questions are all very important. Your HHC needs to put in the hours, and then be willing to assume some level of risk. Tip 4: Do not take their word for it Many times you will receive a letter from your insurer informing you that you will no longer be able to use your current HHC and you will have to switch to the insurer’s preferred provider. Some of these letters are real and some are a scare tactic. You and your HHC should call to see if there are any changes to your plan. A lot of times there are not. It is always good to get the necessary prior authorizations or pre-certifications before shipping just to make sure. Some treatment teams will recommend their patients call their insurer to find out which providers they can use, which is definitely the easiest path to picking your HHC. However, if there were a particular HHC you would like to use, I would not recommend calling your insurer. They will tell you who they want you to use. I would suggest calling the HHC you would like to use and ask them to run your insurance information. A lot of times the HHC can bill differently, such as out-of-network, through a third party payer (TPA), or through your medical plan, which may then allow you to use them. Tip 5: Find out if you have out-of-network benefits This information can be found in your COC. If you or someone in your family has a chronic illness, I always recommend picking a plan with out-of-network benefits, such as a PPO, if you can afford the higher premiums. It not only can affect which HHC you are allowed to use, but also which doctors and which hospitals you are allowed to go to for care. If you do have a plan with out-of-network benefits, it becomes very difficult for insurers to

prevent you from using the HHC of your choice. Unfortunately insurers still find a way to deny people their out-of-network benefits even when they pay extra to have those out-of-network benefits. Some payers have moved factor to their pharmacy benefit, which requires you to use their preferred pharmacy (that they usually own), or they can simply “carve out” hemophilia and mandate which provider people with hemophilia are allowed to use, which is a discriminatory practice. That said, many plans with out-of-network benefits will still allow you to choose your HHC. They may just give you and your HHC the runaround for a while. That is why it is so important to have your COC so you can recite the actual verbiage of your plan. Be aware that when you do exercise your out-of-network benefits, there is usually higher co-pays or deductibles. Ask your HHC if they have a hardship program or if they work with the manufacturer of the brand of factor you use, as almost all of the manufacturers have generous copay assistance programs and patient assistance programs (PAPs). Tip 6: Find out if your plan is fully-funded or self-funded Fully-funded plans are your traditional plans. Self-funded plans are usually plans offered by large employers where the employer pays the claims themselves and they hire an insurer to administer the plan. Again, this can be found in the COC. Employers with self-funded plans usually have an additional insurance policy specifically to offset the cost of an employee with a high cost disorder, such as an inhibitor. There are pros and cons to self-funded plans. A con for self-funded plans would be that they are not regulated by the government. So they could decide not to cover factor. That is usually not the case because good employers want happy employees. But it does happen. That said, the fact that the employer can have a lot more say and has the power to make exceptions would be a major pro for self-funded plans. So if you have a self-funded plan, you would want to go to your HR department and tell them how important it is for you to have access to your HHC. If they value you enough, they can make that change. Tip 7: Find out if factor is covered under your medical benefit or your pharmacy benefit Factor used to always be covered under the major medical benefit. The trend lately has been to

move factor over to the pharmacy benefit. Insurers have a bit more control when factor is billed on the pharmacy side, but we usually have much more freedom to choose our HHC when it is billed on the medical side. Check your COC. It will tell you which side factor is billed on. It will also tell you if there are exceptions. Often times, if a nurse or professional is doing the infusion, the factor can be billed under the medical benefit, which usually allows you to stay with your HHC. Also, if factor is billed under the pharmacy benefit, you are at risk of paying those high specialty tier copays. Tip 8: Ask to appeal If your insurer is telling you that you need to switch to a different HHC, ask if there is an urgent appeal process or special consideration process. Follow that process exactly and act fast…because they do not. You can usually ask your doctor for a letter and your HHC can help you construct a letter from you stating your case. Don’t be afraid to share how difficult life can be, what services you are receiving from your current HHC, and why they are so important. Even though it does not carry the weight it used to, stress how important continuity of care is for your family. Share what you have been through and what could happen if you receive poor services. Tip 9: Contact your hemophilia patient organizations Contact your local, state, regional, or national hemophilia organizations and ask for support. Some organizations are definitely more helpful than others. They may be able to put you in touch with the right individuals. Ask if they can help you prepare or defend your case to your insurer or provide you with up to date info on any insurance law changes in your state. They may also be able to put you in touch with other families who are having the same problems, usually with the same insurer. Your voices together will be much stronger than your voice alone. They may also help get the media involved if it’s a big enough issue. Concluded on page 22

Mark Zatyrka has severe hemophilia A (previously with an inhibitor) and lives in Suffield, CT with his wife and 16 month old twin daughters. He was a previous owner of American Homecare Federation (AHF), and is currently their Director of Marketing. AHF is a homecare company that works exclusively with families living with hemophilia and other bleeding disorders. AHF strives for excellence in providing services to individuals living with inhibitors. Mark is also a founder of the Connecticut Hemophilia Society.

INSURANCE CORNER

NovoSeven® RT responds with speed to control your bleedsa Want to watch a movie at my house tonight?

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My mom says she’ll order pizza, too.

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BRAXTON Braxton has congenital hemophilia with inhibitors a

In people with hemophilia A or B with inhibitors. Median of 2 doses.

Indications and Usage NovoSeven® RT (Coagulation Factor VIIa [Recombinant]) is indicated for the treatment of bleeding episodes in hemophilia A or B patients with inhibitors to FVIII or FIX and in patients with acquired hemophilia; prevention of bleeding in surgical interventions or invasive procedures in hemophilia A or B patients with inhibitors to FVIII or FIX and in patients with acquired hemophilia; treatment of bleeding episodes in patients with congenital Factor VII deficiency and prevention of bleeding in surgical interventions or invasive procedures in patients with congenital FVII deficiency.

Important Safety Information Serious thrombotic side effects are associated with the use of NovoSeven® RT outside of the uses approved by the FDA. These thrombotic side effects are blood clots that form in arteries and veins and can cause harm and may lead to death. Your doctor should discuss the risks and explain the signs and symptoms of thrombotic side effects to you. Your doctor should monitor you for blood clots during treatment with NovoSeven® RT. Thrombotic side effects following the use of NovoSeven® RT occurred in 0.3% of all bleeds that were treated for FDA-approved uses. The rate of 0.2% was observed in hemophilia patients with inhibitors, and the rate was higher in patients with acquired hemophilia (4%). Thrombotic events (fatal and non-fatal) have been reported following use of NovoSeven® RT for all FDA-approved uses. Some patients have conditions that may increase the risk of thrombotic side effects. These include clogged arteries, blood clots that form throughout the body instead of at the place of injury (called disseminated intravascular coagulation), a type of blood poisoning called septicemia, and crush injury, which is when a body part is crushed or squeezed between heavy or immobile objects. Also, people taking aPCCs/PCCs (activated Please see additional Important Safety Information on facing page.

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Important Safety Information (cont’d) or nonactivated prothrombin complex concentrates) at the same time that they are taking NovoSeven® RT may be at increased risk for thrombotic side effects. NovoSeven® RT should be used with caution in patients who have an increased risk for thrombotic side effects. These include, but are not limited to, patients with a history of heart disease, liver disease, patients who have limited movement following surgery, elderly patients, and neonates (babies who are 4 weeks old or younger). In each of these situations, the potential benefit of treatment with NovoSeven® RT should be weighed against the risk of these complications. Some patients with Factor VII deficiency have developed resistance (antibodies) to Factor VII after treatment with NovoSeven® RT. Factor VII-deficient patients should be monitored for antibody formation before and after administration of NovoSeven® RT. People who have ever had a bad reaction to NovoSeven® RT or to proteins from mice, hamsters, or “bovines” (such as an ox or cow) should consult their physician prior to using NovoSeven® RT. The most common side effects in patients treated with NovoSeven® RT are rash, itching, hives, fever, lowered response to treatment, and blood clots in veins. Please see brief summary of Prescribing Information on following pages. 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. NovoSeven® RT is a prescription medicine. Novo Nordisk provides patient assistance for those who qualify. Please call 1-866-310-7549 to learn more about Novo Nordisk assistance programs. Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, New Jersey 08536 U.S.A. NovoSeven® is a registered trademark and MixPro™ is a trademark of Novo Nordisk Health Care AG. © 2014 Novo Nordisk Printed in the U.S.A. 0314-00020735-1 April 2014

NovoSeven® RT Coagulation Factor VIIa (Recombinant) Rx only BRIEF SUMMARY. Please consult package insert for full prescribing information. WARNING: SERIOUS THROMBOTIC ADVERSE EVENTS ASSOCIATED WITH THE USE OF NovoSeven® RT OUTSIDE LABELED INDICATIONS Arterial and venous thrombotic and thromboembolic events following administration of NovoSeven® have been reported during postmarketing surveillance. Clinical studies have shown an increased risk of arterial thromboembolic adverse events with NovoSeven® RT when administered outside the current approved indications. Fatal and non-fatal thrombotic events have been reported. Discuss the risks and explain the signs and symptoms of thrombotic and thromboembolic events to patients who will receive NovoSeven® RT. Monitor patients for signs or symptoms of activation of the coagulation system and for thrombosis. [See Warnings and Precautions] Safety and efficacy of NovoSeven® RT has not been established outside the approved indications. INDICATIONS AND USAGE: NovoSeven® RT, Coagulation Factor VIIa (Recombinant), is indicated for: Treatment of bleeding episodes in hemophilia A or B patients with inhibitors to Factor VIII or Factor IX and in patients with acquired hemophilia; Prevention of bleeding in surgical interventions or invasive procedures in hemophilia A or B patients with inhibitors to Factor VIII or Factor IX and in patients with acquired hemophilia; Treatment of bleeding episodes in patients with congenital Factor VII (FVII) deficiency; Prevention of bleeding in surgical interventions or invasive procedures in patients with congenital FVII deficiency. CONTRAINDICATIONS: None WARNINGS AND PRECAUTIONS: Thrombotic Events within the Licensed Indications: Clinical trials within the approved indications revealed that thrombotic events of possible or probable relationship to NovoSeven® occurred in 0.28% of bleeding episodes treated, with the incidence within hemophilia patients with inhibitors to be 0.20%, and in acquired hemophilia an incidence of 4%. Thrombotic events have been identified through postmarketing surveillance following NovoSeven® RT use for each of the approved indications. The incidence of thrombotic events can not be determined from postmarketing data. Patients with disseminated intravascular coagulation (DIC), advanced atherosclerotic disease, crush injury, septicemia, or concomitant treatment with aPCCs/PCCs (activated or nonactivated prothrombin complex concentrates) have an increased risk of developing thrombotic events due to circulating tissue factor (TF) or predisposing coagulopathy [See Adverse Reactions]. Caution should be exercised when administering NovoSeven® RT to patients with an increased risk of thromboembolic complications. These include, but are not limited to, patients with a history of coronary heart disease, liver disease, disseminated intravascular coagulation, post-operative immobilization, elderly patients and neonates. In each of these situations, the potential benefit of treatment with NovoSeven® RT should be weighed against the risk of these complications. Patients who receive NovoSeven® RT should be monitored for development of signs or symptoms of activation of the coagulation system or thrombosis. When there is laboratory confirmation of intravascular coagulation or presence of clinical thrombosis, the NovoSeven® RT dosage should be reduced or the treatment stopped, depending on the patient’s symptoms. Thrombotic Events outside the Licensed Indications: NovoSeven® has been studied in placebo controlled trials outside the approved indications to control bleeding in intracerebral hemorrhage, advanced liver disease, trauma, cardiac surgery, spinal surgery, and

other therapeutic areas. Safety and effectiveness has not been established in these settings and the use is not approved by FDA. Two meta analyses of these pooled data indicate an increased risk of thrombotic events (10.0% in patients treated with NovoSeven® versus 7.5% in placebo-treated patients). Arterial thromboembolic adverse events including myocardial infarction, myocardial ischemia, cerebral infarction and cerebral ischemia were statistically significantly increased with the use of NovoSeven® compared to placebo (5.3 to 5.6% in subjects treated with NovoSeven® versus 2.8 to 3.0% in placebo-treated patients). Other arterial thromboembolic events (such as retinal artery embolism, renal artery thrombosis, arterial thrombosis of limb, intracardiac thrombus, bowel infarction and intestinal infarction) have also been reported. While venous thromboembolic events such as deep venous thrombosis, portal vein thrombosis and pulmonary embolism have been reported in clinical trials, the meta analysis of these pooled data from placebo-controlled trials performed outside the currently approved indications did not suggest an increased risk of venous thromboembolic events in patients treated with NovoSeven® versus placebo (4.8% in patients treated with NovoSeven® versus 4.7% in placebo-treated patients). In spontaneous reports of women without a prior diagnosis of bleeding disorders receiving NovoSeven® for uncontrolled post-partum hemorrhage, thrombotic events were observed. During this period, patients are at increased risk for thrombotic complications. PostHemostatic Dosing: Precautions should be exercised when NovoSeven® RT is used for prolonged dosing. Antibody Formation in Factor VII Deficient Patients: Factor VII deficient patients should be monitored for prothrombin time (PT) and factor VII coagulant activity before and after administration of NovoSeven® RT. If the factor VIIa activity fails to reach the expected level, or prothrombin time is not corrected, or bleeding is not controlled after treatment with the recommended doses, antibody formation may be suspected and analysis for antibodies should be performed. Hypersensitivity Reactions: NovoSeven® RT should be administered with caution in patients with known hypersensitivity to NovoSeven® RT or any of its components, or in patients with known hypersensitivity to mouse, hamster, or bovine proteins. Laboratory Tests: Laboratory coagulation parameters (PT/INR, aPTT, FVII:C) have shown no direct correlation to achieving hemostasis. Assays of prothrombin time (PT/INR), activated partial thromboplastin time (aPTT), and plasma FVII clotting activity (FVII:C), may give different results with different reagents. Treatment with NovoSeven® has been shown to produce the following characteristics: PT: As shown below, in patients with hemophilia A/B with inhibitors, the PT shortened to about a 7-second plateau at a FVII:C level of approximately 5 units per mL. For FVII:C levels > 5 units per mL, there is no further change in PT. The clinical relevance of prothrombin time shortening following NovoSeven® RT administration is unknown. PT (sec) 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 0

PT versus FVII:C

30 20 FVII:C (unit per mL)

INR: NovoSeven® has demonstrated the ability to normalize INR. However, INR values have not been shown to directly predict bleeding outcomes, nor has it been possible to demonstrate the impact of NovoSeven® on bleeding times/ volume in models of clinically-induced bleeding in healthy volunteers who had received Warfarin, when laboratory parameters (PT/INR, aPTT, thromboelastogram) have normalized. aPTT: While administration of NovoSeven® shortens the prolonged aPTT in hemophilia A/B patients with inhibitors, normalization has usually not been observed in doses shown to induce clinical improvement. Data indicate that clinical improvement was associated with a shortening of aPTT of 15 to 20 seconds. FVIIa:C: FVIIa:C levels were measured two hours after NovoSeven® administration of 35 micrograms per kg body weight and 90 micrograms per kg body weight following two days of dosing at two hour intervals. Average steady state levels were 11 and 28 units per mL for the two dose levels, respectively. ADVERSE REACTIONS: The most frequently reported adverse reactions in patients treated with NovoSeven® are rash, pruritus, urticaria, pyrexia and venous thromboembolic events occurring in > 0.1% to < 1% of patients. Therapeutic response decreased has also been reported at a similar rate. It is important that the dosage regimen of NovoSeven® is compliant with the recommended dosage in the package insert. Clinical Trials Experience: Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug product cannot be directly compared to rates in clinical trials of another drug, and may not reflect rates observed in practice. Thrombotic events following the administration of NovoSeven® occurred in 0.3% of bleeding episodes treated, with the incidence in acquired hemophilia of 4% and in hemophilia patients of 0.2% in clinical trials within the approved indications [See Warnings and Precautions]. Adverse reactions observed in clinical trials for all labeled indications of NovoSeven® included pyrexia, injection site reaction, headache, hypertension, nausea, vomiting, pain, edema, rash (including allergic dermatitis and rash erythematous), pruritus, urticaria, hypersensitivity, cerebral artery occlusion, cerebrovascular accident, pulmonary embolism, deep vein thrombosis, angina pectoris, increased levels of fibrin degradation products, disseminated intravascular coagulation and related laboratory findings including elevated levels of D-dimer and AT-III, thrombosis at i.v. site, non-specified thrombosis, thrombophlebitis, superficial thrombophlebitis. The following sections describe the adverse event profile observed during clinical studies for each of the labeled indications. Hemophilia A or B Patients with Inhibitors: Two studies (Studies 1 and 2) are described for hemophilia A or B patients with inhibitors treated for bleeding episodes. The table below lists adverse reactions that were reported in ≥2% of the 298 patients with hemophilia A or B with inhibitors that were treated with NovoSeven® for 1,939 bleeding episodes. # of episodes # of unique Body System reported patients Reactions (n=1,939 treatments) (n=298 patients) Body as a whole Fever 16 13 Platelets, Bleeding, and Clotting 10 5 Fibrinogen plasma decreased Cardiovascular Hypertension 9 6 Other reactions reported in 1% of patients were: allergic reaction, coagulation disorder, DIC, edema, fibrinolysis increased, headache, injection site reaction, pain, pruritus, purpura, rash, thrombosis and therapeutic response decreased. Serious adverse reactions occurred in approxi-

mately 3% of the patients and included thrombosis, pain, thrombophlebitis deep, pulmonary embolism, therapeutic response decreased, cerebrovascular disorder, angina pectoris, DIC, anaphylactic shock and hepatic function abnormal. The serious adverse reactions of DIC and therapeutic response decreased had a fatal outcome. Surgery Studies: Two clinical trials (Studies 3 and 4) were conducted to evaluate the safety and efficacy of NovoSeven® administration during and after surgery in hemophilia A or B patients with inhibitors. In one study (Study 3), two patients had adverse reactions (acute post-operative hemarthrosis and internal jugular thrombosis). No deaths occurred during the study. In another study (Study 4), four of 24 patients had serious adverse reactions, all being decreased therapeutic response. Two reactions were observed in each treatment arm (bolus injection and continuous infusion). No deaths occurred during the study period. Postmarketing Experience: The following adverse reactions have been identified during post approval use of NovoSeven®. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship. These adverse reactions were reported following the use of NovoSeven® in labeled and unlabeled indications that included individuals with and without coagulopathy: high D-dimer levels and coagulopathy, thrombosis, thrombophlebitis, arterial thrombosis, and thromboembolic events including myocardial ischemia, myocardial infarction, cerebral ischemia, cerebral infarction, renal artery thrombosis, intracardiac thrombus, portal vein thrombosis, thrombophlebitis, peripheral ischemia, deep vein thrombosis and related pulmonary embolism, injection site pain, headache, nausea and isolated cases of hypersensitivity/allergic reactions including anaphylactic shock, flushing, urticaria, rash, and angioedema [See Warnings and Precautions]. Fatal and non-fatal thromboembolic events have been reported with use of NovoSeven® when used for off-label or labeled indications. There have been no confirmed reports on inhibitory antibodies against NovoSeven® or FVII in patients with congenital hemophilia A or B with alloantibodies. The Hemophilia and Thrombosis Research Society (HTRS) Registry surveillance program is designed to collect data on the treatment of congenital and acquired bleeding disorders. All prescribers can obtain information regarding contribution of patient data to this program by calling 1-877-362-7355 or at www.novosevensurveillance.com. Congenital Factor VII Deficiency: Data collected from the compassionate/emergency use programs, the published literature, a pharmacokinetics study, and the Hemophilia and Thrombosis Research Society (HTRS) registry showed that at least 75 patients with Factor VII deficiency had received NovoSeven® - 70 patients for 124 bleeding episodes, surgeries, or prophylaxis regimens; 5 patients in the pharmacokinetics trial. In the compassionate/emergency use programs, 1 non-serious adverse reaction (intracranial hypertension) and 1 serious adverse reaction (IgG antibody against rFVIIa and FVII) were reported. One adverse reaction (localized phlebitis) was reported in the literature. No adverse reactions were reported in the pharmacokinetics reports or for the HTRS registry. No thromboembolic complications were reported for the 75 patients included here. As with all therapeutic proteins, there is a potential for immunogenicity. In compassionate/emergency use programs patients with factor VII deficiency formation of antibodies against NovoSeven® and FVII (frequency: common (≥ 1/100 to < 1/10)) have been reported. In some cases, the antibodies showed inhibitory effect in vitro. Risk factors that may have contributed to antibody development including previous treatment with human plasma and/or plasma-derived factor VII, severe mutation of FVII gene, and overdose of NovoSeven®, were present. Patients with factor VII deficiency treated with NovoSeven® should be monitored for factor VII antibodies. Acquired Hemophilia: Data collected from four compassionate use programs, the HTRS registry, and the published literature showed that 139 patients with acquired hemophilia received NovoSeven® for 204 bleeding episodes, surgeries and traumatic injuries. Of these 139 patients,

6 experienced 8 serious adverse reactions. Thrombotic serious adverse events included cerebral artery occlusion, cerebral ischemia, angina pectoris, myocardial infarction, pulmonary embolism and deep vein thrombosis. Additional serious adverse reactions included shock and cerebrovascular accident. Three of the serious adverse reactions had a fatal outcome (shock, cerebral artery occlusion and myocardial infarction). OVERDOSAGE: There are no adequate and well controlled studies to support the safety or efficacy of using higher than labeled doses in the indicated populations. Dose limiting toxicities of NovoSeven® RT have not been investigated in clinical trials. The following are examples of accidental overdose. Congenital Factor VII Deficiency: A newborn female with congenital factor VII deficiency was administered an overdose of NovoSeven® (single dose: 800 micrograms per kg body weight). Following additional administration of NovoSeven® and various plasma products, antibodies against rFVIIa were detected, but no thrombotic complications were reported. A Factor VII deficient male (83 years of age, 111.1 kg) received two doses of 324 micrograms per kg body weight (10-20 times the recommended dose) and experienced a thrombotic event (occipital stroke). Hemophilia A or B with Inhibitors: One hemophilia B patient (16 years of age, 68 kg) received a single dose of 352 micrograms per kg body weight and one hemophilia A patient (2 years of age, 14.6 kg) received doses ranging from 246 micrograms per kg body weight to 986 micrograms per kg body weight on five consecutive days. There were no reported complications in either case.

More detailed information is available upon request. For information contact: Novo Nordisk Inc. 100 College Road West Princeton, NJ 08540, USA 1-877-NOVO-777 www.NovoSevenRT.com Version: 20121203-V7 Manufactured by: Novo Nordisk A/S 2880 Bagsvaerd, Denmark Novo Nordisk® is a registered trademark of Novo Nordisk A/S. NovoSeven® is a registered trademark of Novo Nordisk Health Care AG. © 1998-2013 Novo Nordisk 0113-00012931-1 1/13

Overview

oday, nearly 40 years after effective treatments

FVIII is often the only treatment option patients are

are many of us living with an inhibitor that causes

FVIII products work the same for each of us. Some of

for hemophilia A became widely available, there

uncontrolled bleeding episodes, increased disability and decreased quality of life. For some of us, these effects can be compared to those individuals who

lived with hemophilia prior to factor replacement. In approximately 30% of all individuals with severe hemophilia A, inhibitors form in response to FVIII therapy, rendering any routine treatment ineffective.

Due to the history of pathogen transmission in the 70’s

and mid 80’s from human-source FVIII, recombinant

given. As many of us have discovered, however, not all

us have found that after years of unsuccessfully trying to treat with different recombinant products, bleeding

episodes can be managed better with human-source FVIII.

Due to the changes and advances in plasma

collection, manufacturing and production over the past 20 years, perhaps it is reasonable to consider human-

source FVIII as an option for patients with difficult to treat symptoms of hemophilia A.

“Not all treatments work the same for each patient. We need more options to choose from than just more recombinant FVIII.” -Eric Lowe

LIFELINES for HEALTH

Summer 2014

History of Factor VIII Human-source FVIII became widely

available

the

1970’s,

allowing

hemophilia A patients, for the first time, to

treat bleeding episodes at home, to travel and to have surgery.1

These products

created a significant improvement in the quality of life for individuals with

hemophilia. Lengthy hospital stays and

lengthy treatments became a thing of the past. The lifespan of an individual with

hemophilia A could now be increased dramatically.

It wasn’t long after

their introduction however, that it was

discovered the use of human-source FVIII

carried a risk of pathogen transmission. Many of us had family members who became infected in the 1970’s and 1980’s. It was by far the most tragic era in the history of hemophilia treatment.

“Because of my inhibitor, it had been years since my treatments worked as they should. I spent a lot of time doing my own research. It took a move and a change in treatment teams before I had a discussion with my doctor about human-source FVIII. I only wish we had that discussion earlier.” -Jake Rollins

Recombinant versions of FVIII, first

introduced in the early 1990’s,1 were

not just hailed as welcome additions to the hemophilia A treatment toolbox,

but signified a complete change in the way we treat hemophilia A to this day.

Along with increased product choice and

supply of available treatments, the risk of pathogen transmission was significantly decreased. Prophylaxis treatment became the standard of care, drastically reducing

the number and severity of bleeds and the subsequent joint damage they cause.

For many of us, prophylaxis meant the ability to live an otherwise “normal” life with the opportunities to participate in sports and other activities that would have

been considered too risky, dangerous or impossible.

FEATURE

Inhibitor Development Necessitates a New Outlook Managing a chronic neutralizing

was successfully completed with human-

Its’ impact on the individual and

It is highly doubtful that there is

inhibitor is a daunting challenge. the family’s overall quality of

a single medication, prescription or

us have spent precious years

of side effects, some more harmful than

life is debilitating. and

resources

(ITI)

with

Many of

attempting

immune tolerance induction

infusions

FVIII,

large,

frequent

recombinant

large,

frequent

volumes of bypassing agents with

little to no success.

The options

for treatment are extremely limited,

the risks, consequences and benefits of any medication we use. Our community

should never forget the devastating effects of products that were not stringently screened, tested and manufactured.

The biggest challenge in the hemophilia

them, we do know that at least 30% of

community’s history, as a way to manage bleeding episodes soon became the only

choice for many of us. Faced with a diminished quality of life, many of us

source plasma on our own as a possible

treatment option. What was found was

to FVIII products. There are those of

child’s) health, it is imperative to know

FVIII – not an easy choice given our

began researching the safety of human-

We do not all have the same response

others. As stewards of our own (or our

community today is inhibitors. Although

consulted with our medical teams or

Final Thought

otherwise that does not carry the risk

while the bleeds and complications are

abundant. Reconsidering human-source

“Inhibitors had reduced our quality of life to the point where we were open to trying anything.” -Janet Brewer, M. Ed.

source product.

that our bleeding episodes could again be

managed. For many, immune tolerance

no one can say with certainty what causes

the severe hemophilia A population will develop one. We as custodians of our own

(or child’s) health in conjunction with

our health care team need to know all of

the options for treatment available to us, along with their possible consequences. This knowledge for those of us living

with an inhibitor could make a drastic difference in bleed management, joint health and overall quality of life.

us who develop inhibitors or are poor half-life responders. We have learned that some of us do respond successfully to human-source FVIII products.

No one knows for sure why, but

after years of uncontrolled bleeding,

many of us wish we had considered human-source products long ago. We

would like to encourage physicians, nurses, and caregivers that it is okay

to bring up the topic of human-source

Authored by:

References

Jake Rollins - Adult with severe hemophilia A. Human-source FVIII successfully tolerized his inhibitor.

Lusher JM. Development and introduction of recombinant factor VIII - a children’s experience. Haemophilia. 2012;18:483-86

Viel KR, Afshin A, Abshire TC, lyer, RV et.al. Inhibitors of Factor VIII in black patients with hemophilia. N Engl J Med. 2009;360:1618-27.

www.pptaglobal.org Plasma Protein Therapeutics Association (PPTA)

Klamroth R et al. Pathogen inactivation and remocal methods for plasma-derived clotting factor concentrates. Transfusion. 2013:9.

Janet Brewer - Mother of 2 sons with severe hemophilia A. One of her sons developed an inhibitor which was partially tolerized after switching to human-source FVIII. Eric Lowe - Adult with severe hemophilia A. Human-source FVIII successfully tolerized his inhibitor.

FVIII products in the discussion with patients and parents, and vice-versa.

LIFELINES for HEALTH

Summer 2014

Manufacturing of Human-Source FVIII: A Multi-Step Process The hemophilia community will always be a strong, unified voice in its’ demand for highest, safest, worldwide manufacturing standards to ensure that all treatments for hemophilia are safe. The multi-step screening and test procedures implemented over the last several decades have significantly improved the safety of human-source FVIII. The entire process from donor collection to final product release takes from 7-9 months.

Donor Screening and Testing 1.

Only donations from qualified donors are used. Requirements include: • An extensive health questionnaire and physical examination • Donor must return for a second donation in order for the first donation to be released into production: • The highest risk donor is the first-time donor • Both donations must test negative for transmissible viruses

Donation Testing - Potential viral contamination is determined in two ways: • Serology tests for the body’s response to potential infection by HIV, Hepatitis B, Hepatitis C, and Parvovirus. • Nucleic acid amplification testing (NAT) tests for the presence of very small amounts of nucleic acids from Hepatitis A, B and C; HIV and Parvovirus

Plasma Inventory Management • Each donation is bar coded and held for up to 60 days: • Allows for the identification, retrieval and destruction of any donation disqualified as a result of positive viral testing or post-donation information • Any high-risk donor, and any testing “reactive” for HIV, Hepatitis B or Hepatitis C are placed on the National Donor Deferral Registry (NDDR) and are permanently prohibited from donating

Manufacturing Pool Testing • Cleared donations are combined into manufacturing pools and undergo additional viral testing

Safe Manufacturing3,4 5.

Purification - While purifying FVIII, chromatography removes unwanted material

Viral Inactivation steps - products use various methods including: • Solvent/Detergent Treatment - dissolves “enveloped” viruses, including HIV and Hepatitis B and C • Dry Heat Treatment - Inactivates “non-enveloped” viruses, including Hepatitis A and parvovirus • Pasteurization - wet heat treatment • Sodium thiocynate and others

Industry Safety Standards Today, the Plasma Protein Therapeutic Association (PPTA)3 administers rigorous safety standards for the entire industry ensuring that human-source FVIII is safe for our use: International Quality Plasma Program (IQPP) - provides certification for donor centers based on rigorous safety standards

National Donor Deferral Registry (NDDR) - any donor testing “reactive” for infectious agents is permanently barred from donation.

Quality Standards of Excellence, Assurance and Leadership (QSEAL) - voluntary manufacturing standards that go beyond regulatory requirements, including rigorous donor screening and donor testing procedures, 60-day donor holds, donation testing and viral inactivation steps.

Patient Notification System (PNS) - Notifies patients directly of recalls of plasma products (rather than informing only physicians and pharmacists). Free registration is available at: www.patientnotificationsystem.org.

FEATURE

Inhibitor Crossword Across 1. Pain relieving method 5. Therapy for eliminating inhibitors (abbr.) 7. Surgically enlarged vein for infusions 10. ______ the factor! (Lingo for the unadvised practice of infusing too quickly) 12. Infusion aiding implant 15. Additional clotting factor sometime used for ITI (abbr.) 16. Uncommon being, like someone with a bleeding disorder 17. State of the Lone Star Chapter of NHF 18. Factor isn’t a “want”, it’s a ______ 19. Brand name for 42-across 21. Kryptonite for hemophilia 24. Factor fighters 26. If this provides factor, it’s a 340b (abbr.) 27. USA’s illness consultant (abbr.) 30. Surprisingly debilitating location for a joint bleed 31. Synonym for “pain” 32. Popular location for a target joint 34. Generic term for “infusion” 36. “Right back ______ ______! (2 words) 37. Describes hemophilia in a genetic manner 39. A good reason to infuse, or a season 41. Twenty years ago, hemophilia was only recognized in a ______

LIFELINES for HEALTH

42. Compresses injured body part 43. Honest U.S. president rumored to have had hemophilia 44. Used to treat bleeds in the 50’s 46. Pain meds can cause you to do this 47. State of “Delaware Valley” & “Western” hemophilia foundations

Down 1. Infusion step that precedes the poke 2. Falling off your bike gave me a good ______! 3. State of “Mountain States Regional” HTC 4. Unit of measurement for inhibitors 6. Use of cryoprecipitate and clotting factor in the 60’s mark the end of an ______. 8. Another name for 5-across (abbr.) 9. Describes an irregular infusion regimen 11. Roman talk for Factor 8 13. Musculoskeletal surgery (abbr.) 14. Vacation ______ are too often replaced by ER ______. (same name) 19. Used to perform 1-down 20. Famous game show saying, “I’d like to use one of my ______, Regis.” 22. 24/7 department of a hospital 23. Hemophilia support group founded in 1948 (abbr.)

Summer 2014

24. Old-fashioned bleed-stopper 25. Hemophilia support group founded in 1994 (abbr.) 28. Strange, Love, & Kevorkian 29. Employee for a pharma company 33. Frightening factor delivery tool 35. Inhibitor Family _______ 37. The _________ Disease (refers to

Hemophilia B) 38. Place of blood testing 39. What pain does during the healing process, also a men’s hairstyle 40. “It’s not a _______, it’s a swagger.” 44. A location of sentencing during a bleed Answers on page 22

FUN & INSPIRATION

Blake

is an eleven-year-old baseball player with hemophilia A, severe, who has battled and triumphed with inhibitors over the years. This is his story of yet another triumph in his life - his ability to follow his dreams and passions without letting the challenges of hemophilia stop him. Thank you Blake, for sharing your amazing story and giving us hope!

My Right Arm by Blake Katzman

s I came back to the orthopedists office with my mom to see what was making my arm act so funny, I shivered and quaked with fear in the cold barren office. Right when the doctor walked in, she wasn’t smiling at all; instead her face was stern looking with bits of nervousness. By the looks of it, none of it was what I hoped for. “Blake, you seem to have a loose particle floating in your elbow area and there is not enough synovial fluid between your elbow joint. I am sorry to say that you can not play any throwing sports,” the orthopedist described. “It’s from all the bleeds that you had in your elbow over the last few years,” my mother exclaimed!

I was shocked to hear this news and was aggravated and shattered over the tragedy! My eyes streamed down salty, bitter tears of anger. “How can I fix it?” I mourned. There is surgery but we don’t want to damage your flexibility,” the orthopedist explained. “It’s okay Blake you can still do all sports at camp,” my mother whispered in my ear. By now I sobbed even harder, tears pelted against my shirt leaving big splotches of liquid on me. After a little bit I calmed down and tried bending my arm. I heard a crack that made me want to sob again but I held the water back. Suddenly I thought, maybe I will learn how to use my left arm for sports. How will I ever get my arm to the strength to be able to throw a ball? I knew it would take months to get to the level to be able to do

that. I was determined to make it happen. I knew I would only be allowed to do swimming for now until there are safer and easier ways to repair my joint. With strong determination and sheer will I can now throw as good with my left arm as I used to be able to with my right arm. My mom tells me that she is proud of me and what I have done. I am proud of me too. It wasn’t easy but then again most of what I have gone through hasn’t been either!

FUN & INSPIRATION

NEW!

Products Available RIXUBIS, by Baxter

Hemophilia B

TRETTEN, by Novo Nordisk

FXIII A-Subunit The U.S. Food and Drug Administration (FDA) approved Tretten, Coagulation Factor XIII A-Subunit (Recombinant) - the first recombinant product for use in the routine prevention of bleeding in adults and children who have (the very rare) Factor XIII A-subunit deficiency. Ideal Prophylactic Treatments: once per month

RIXUBIS [Coagulation Factor IX (Recombinant)] is now available for adults with hemophilia B. RIXUBIS is the only FDA-approved recombinant factor IX indicated to treat adults age 16 years and older with hemophilia B for the following. Approved for: • • •

Routine prophylaxis to prevent or reduce the frequency of bleeding episodes Control and prevention of bleeding episodes Use with surgery

Ideal Prophylactic Treatments: twice per week

For more information, visit rixubis.com or speak with your Baxter rep

For more information, visit tretten-us.com

ELOCTATETM, by Biogen Idec

Hemophilia A

The FDA has approved ELOCTATETM [Antihemophilic Factor (Recombinant), Fc Fusion Protein] - the first and only factor VIII with a prolonged half-life indicated in adults and children with hemophilia A. Approved for: • • •

Control and prevention of bleeding episodes Surgical prophylaxis Routine prophylaxis to prevent or reduce the frequency of bleeding episodes

ALPROLIXTM, by Biogen Idec

Hemophilia B Recently, the FDA approved ALPROLIX™ [Coagulation Factor IX (Recombinant), Fc Fusion Protein] - the first recombinant, hemophilia B therapy that provides protection from bleeds starting with at least a week between prophylactic infusions. Protection is defined as the prevention of bleeding episodes using a prophylaxis regimen. Approved for: • • •

Control and prevention of bleeding episodes Use during the surgical process Routine prophylaxis in adults and children with hemophilia B

Ideal Prophylactic Treatments: once every 3-5 days

Ideal Prophylactic Treatments: once every 7-10 days

ELOCTATE

ALPROLIX™ is not indicated for immune tolerance induction therapy, which is a treatment for people with inhibitors.

is not indicated for von Willebrand disease.

For more information, please visit ELOCTATE.com

For more information, please visit ALPROLIX.com

LIFELINES for HEALTH

Summer 2014

BLOODLINES

As you know, Living with an Inhibitor can be complicated & difficult. Let AHF give you a few extra hands. AHF is the homecare that specializes in providing services to children and adults Living with Inhibitors AHF once again received a 100% satisfaction rating from their family of clients. We earned our reputation by providing the highest quality of services around and providing endless support to the bleeding disorders community. AHF_Hemophilia fb.com/AHF-Hemophilia-Services Supporting Our Community

Personalized Services

(800) 243-4621 | AHF@AHFinfo.com | www.AHFinfo.com

Maintaining Your Preferred Specialty Pharmacy Provider Concluded from page 10. Tip 10: Contact your state legislator This is one of the reasons why it is always great to keep a relationship with your state legislators. Many of them are now very familiar with the behaviors of insurers. Try to be proactive and contact them before the change occurs. You can also contact your state’s Attorney General, Insurance Commissioner, and even the Governor. If your efforts fall short and you are not able to stay with your HHC, here are a couple more tips to keep in mind. Tip 11: Keep good notes If you feel like the new pharmacy is not providing you with sufficient services, you need to start keeping detailed notes. Every time your new

them about hemophilia and what they need to do. I know it is not your job, but we all need support…and factor!

pharmacy messes up, write it down. That way you can take that journal to your insurer and show them that you are not receiving adequate care and you do not feel safe staying with their preferred provider.

Tip 12: Contact your state legislator, Attorney General, Insurance Commissioner and Governor - again This time you can show them your journal; explain what is going wrong, and what can happen if this issue isn’t resolved. Tip 13: Start educating If you are still not receiving sufficient services, do your best to provide education to your new pharmacy. Teach

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Crossword Answers from page 19

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INSURANCE CORNER

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CHESTM Mission To Inspire awareness and selfreliance for patients with chronic health conditions, their families, and their communities.

Editors in Chief Janet Brewer, M. Ed. Eric Lowe

Publication Designer Eric Lowe

Contributing Writers: Sha Ha Blake Katzman Justin Levesque Mark Zatyrka Lily Zhao Ryan Zhao

Contributing Editors: Kathy Arnaldo

Contributing Content and Production: Joan Ward

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