Hemophilia Renaissance - Kelley Com Technologies and Gene Transfer for Hemophilia, held ... choco late ice cream, and embraces life with all his heart. They have a bond as brothers,

W“We are living in the most exciting time in the history of thetreatment of hemophilia.” This opinion was shared by manyof the 100 physicians and researchers attending NationalHemophilia Foundation’s (NHF) 11th biennial workshop,Novel Technologies and Gene Transfer for Hemophilia, heldin March in Philadelphia.

Why the optimism? World-renowned pioneer in hemo-philia treatment Dr. Edward Tuddenham says we are in themidst of a “Renaissance of product development.” More than30 biosimilar (generic) factor products, extended half-lifeproducts, or enhanced-activity factors are in development.Novel treatments are being tested, including ways to eliminatethe need for factors VIII or IX. Research into the immune

system may show us ways to reduce the risk of inhibitors.Of course, we’ve also made steady advancements in ourknowledge of gene therapy.

New products hitting the market in the next few years willoffer you more treatment choices. Will you switch to a newproduct even when your current product is safe and effective?Are there risks in switching? Should you participate in aclinical trial for a new product or for gene therapy?

The goal of this special feature article is first, to outlinethe major areas of research in hemophilia treatment, andsecond, to help you be a better-informed consumer. Whennew products and treatments become an option, you’ll knowwhat questions to ask.

Parent Empowerment Newsletter LA Kelley Communications, Inc.

inside3 As I See It: Hemophilia the Second Time Around

4 Inhibitor Insights: Wishful Thinking

5 Richard’s Review: Hemophilia in Science Fiction

6 Pulse on the Road: Aloha!

May 2012 • Volume 22 • Issue 2

page 7

New Treatments & Gene Therapy

Paul Clement

Hemophilia Renaissance

Iwas sorting through a pileof photos recently from my24 years in the hemophilia

community, preparing themfor the scanner in an attemptto go completely digital. Ienjoyed the nostalgic feelings Ihad looking at them, recallinga particular NHF meeting or acertain hemophilia summercamp, smiling at how youngwe all looked, and marveling

at the little boys I know who are now men. I’ve beensending the original photos, once I’ve scanned them, outto colleagues and friends to enjoy and remember.One photo really caught my eye before I popped it

into the envelope: a mom from Massachusetts and me,posing together at an NHF meeting. Behind us hung abig sign: “Campaign for the Cure.”Remember the campaign? In the mid-1990s, there

was a concerted effort to raise money to fund a cure for hemophilia. Sadly, the campaign fell by the wayside when a young man with a chronic disorder died whilein a clinical gene therapy trial in 1999. Many researchersbecame skittish and fearful of liabilities, and gene therapybegan to disappear, even though this case was not relatedto hemophilia. It seemed then that gene therapy would never

become a reality for our community. But there’s stillhope. In this issue, Paul Clement reviews not only the quest for gene therapy, but the progress of currenttechnologies that improve quality of life for people withbleeding disorders. From gene therapy to longer-actingfactor, you can stay hopeful that a better life is alwayscoming for our loved ones.I look forward to the day when I take no more photos

of my hemophilia days, when I close the doors to mybusiness, when hemophilia becomes history.

2 Parent Empowerment Newsletter | May 2012

PEN is a newsletter for families and patients affected bybleeding disorders. PEN is published by LA Kelley Communications,Inc., a worldwide provider of groundbreaking educationalresources for the bleeding disorder community since 1990.

PEN respects the privacy of all subscribers and registeredpatients and families with bleeding disorders. Personalinformation (PI), including but not limited to names, addresses,phone numbers, and email addresses, is kept confidential andsecure by the LA Kelley Communications editorial staff in accordance with our privacy policies, which can be viewed inentirety on our website. PEN publishes information with writtenconsent only. Full names are used unless otherwise specified.

PEN is funded by corporate grants or advertisements.Sponsors and advertisers have no rights to production, content,or distribution, and no access to files. The views of our guestwriters are their own and do not necessarily reflect the viewsof LA Kelley Communications, Inc., or its sponsors.

PEN is in no way a substitute for medical care or personalinsurance responsibility. Parents or patients who question aparticular symptom or treatment should contact a qualifiedmedical specialist. Parents or patients with personal insurancequestions should contact their employer’s human resourcedepartment, Medicaid or Medicare caseworker, payer representa-tive, or HTC social worker.

Articles may be reprinted from PEN only with expresswritten permission from the editor, and with proper citation.PEN and/or its articles may not be published, copied, placed on websites, or in any way distributed without express writtenpermission.

PARENT EMPOWERMENT NEWSLETTERMAY 2012

EDITOR-IN-CHIEF Laureen A. Kelley | SCIENCE EDITOR Paul Clement

CONTRIBUTING WRITERS | Richard J. Atwood • Jo Schaffel

MANAGING EDITOR Sara P. Evangelos | LAYOUT DESIGNER Tracy Brody

DIRECTOR, MARKETING Kathryn Ondek

DIRECTOR, PROJECT SHARE Zoraida Rosado

65 Central StreetGeorgetown MA 01833 USA

978-352-7657 • fax: [email protected] • www.kelleycom.com

welcome

inbox

Laurie Kelley

Credit for the photos in this issue, unless otherwise noted: Copyright © 2012 LA Kelley Communications, Inc. and itslicensors. All rights reserved.

THANK YOU FOR THE PACKAGE [OF BOOKS] YOU SENT US.We received it just before Christmas, and it was one ofthe best gifts we received. We just recently had a port putin our seven-month-old son. He did great; bounced rightback to his normal happy self! I want to let you knowhow much we appreciated your reaching out to us. Whenwe first found out about our son, we were so scared. Butthanks to the support from people like you, we feel somuch better about our situation and count our blessingsevery day!Armida McDowellCalifornia

page 19

Cazandra Campos-MacDonald

Parent Empowerment Newsletter | May 2012 3

Day and Night: Hemophilia the Second Time Around

as i see it

My boys are like day andnight. My 15-year-old, Julian,is a free spirit: creative, artistic,

a great sense of humor, and a giftedmusician. His idea of a perfect day isto be in New York City watchingBroadway shows. My 5-year-old,Caeleb, adores choo-choo trains andplaying in the dirt, can’t get enoughchocolate ice cream, and embraces lifewith all his heart. They have a bond asbrothers, and they also share the bondof severe hemophilia A.Julian was almost 10 when Caeleb

was born. When my husband Joe andI broke the news to Julian that his littlebrother also had hemophilia, heclapped and jumped for joy! We werestunned. Why was he so excited?“When I am in leadership training atcamp,” Julian replied, “he will be acamper!” My sweet son saw only thecommonalities and blessings of hemo-philia. He would share one of his most

exciting summer activities with hisbaby brother.But my boys don’t share everything.

Caeleb wants to go to a monster truckrally, and Julian loves watching livetheater. Caeleb is a social butterfly,while Julian keeps to himself. And asfor hemophilia, they can’t even beginto compare adventures.Julian’s hemophilia has been pretty

easy so far. No major bleeds or targetjoints, and a port that lasted five yearswithout infection. Caeleb, on the otherhand, has a target joint and suffersfrom extremely painful bleeds. He ison his fourth port, fights a high-titerinhibitor, and has been hospitalizedoften. With ten years’ differencebetween my boys, at times I still feellike a “newly diagnosed” parent.During one of Caeleb’s hospital

stays, the nurses were having a toughtime starting an IV. Poke after poke,nurse after nurse, and my Julian, 12at the time, was standing outside theroom crying silent tears for hisbrother. His knowledge of empathyand compassion will always be withhim. He loves deeply. As for Caeleb,when he has an infusion or blood drawperipherally, despite his fear, he trieshis hardest not to “cry and wiggle,” sohe can “be like his big bro.”My sons and their hemophilia differ

significantly—you’d almost think theyhave different severity levels and evendifferent bleeding disorders. But amedical condition may manifest in itsown way in each person: what is day

to one becomes night to another.Over the past five years, our familyhas spent immense time and energylearning to live with Caeleb’s hemo-philia. It’s been challenging, comparedto the ten years before Caeleb’s birth,but one thing’s for sure: my boysstruggle with their bleeding disorderin different ways, and it has bondedthem together.In 2010, while I was out of town,

Caeleb’s port was not working and myhusband had to access him peripherally.Caeleb was having an active bleed,and infusing him was an emergency;we live two hours from the hemophiliatreatment center. Instead of letting hislittle brother be uncomfortable andscared, Julian sat with him, explainedwhat was going to happen, and neverstopped holding his hand. His encour-agement helped my husband focus onthe actual infusion instead of having tokeep Caeleb calm. My husband neverprompted Julian to help. Julian justrose to the occasion and did whatbrothers do.No one chooses to have a chronic ill-

ness. It just happens. Hemophilia haschanged my family—it has brought outthe best in us all. My husband and I arecloser than ever in our 22 years together.The reality of hemophilia can damageand destroy relationships, but luckily, wehave made it through stronger thanbefore. Of course, if I could banishhemophilia, I would in a second! Andyet, I have so many blessings in my lifethat if I could give them away, it would

page 18

Cazandra and her husband Joe, with sons Julian and Caeleb, and a special guestat Give Kids the World Village in Kissimmee, Florida. Make-A-Wish Foundationgranted Caeleb's wish to visit Disney World.

Julian and his younger brother Caeleb

photos: Campos-MacDonald family

A

“I would love to see a longer-lasting VIIa.”

“A medicine that would eliminate aninhibitor.”

“Products that don’t cause inhibitors inthe first place.”

Are any of these on your wish list for new or improvedinhibitor products?Wouldn’t it be great to have a fairy godmother (or a genie

in a magic lamp) who could grant any wish? How about aninhibitor product that would last days or weeks instead of justa few hours? Maybe even one that didn’t have to be givenintravenously? In our real world, we don’t have fairy godmothers or

genies (oh well), but there are scientists, doctors, andresearchers who are working on some of the items on ourwish lists.

Wishes for... Faster-acting or longer-lasting factorFactor products that last longer in the bloodstream are at thetop of many inhibitor family wish lists. Advances in biotech-nology are raising hopes that faster-acting or longer-lastingtherapies and treatments for inhibitors will be available in thenext few years.Debbie Porter of California is one mother who’d like to

see products last longer. “I mean long lasting,” she explains,“not just an hour or two more—I’m talking days or weeks.”Medically, inhibitor bleeds can mean days in the hospitalcoping with pain. And bleeds are often more frequent ininhibitor patients because of multiple target joints. A longer-lasting product would possibly reduce the frequency andhelp preserve the joints. A bleed also means a child misses many days of school, or

an adult misses many days of work. Dosing frequently forseveral days to heal a bleed can be tough, especially in children,who have trouble sitting still in the best of circumstances.Cicely, who has a son with inhibitors, would also like to seeproducts that last longer than the ones currently available.“Longer-acting VIIa would be wonderful, especially for theinhibitor patients, like my son, who have joint bleeds everyday.” She notes, “The hardest thing we face is keeping a veryactive boy immobile while healing, to prevent re-bleeding.”Yes, life can be tough for inhibitor patients. The good news is

that several companies are now working on longer-lasting recom-binant factor VIIa. CSL Behring is testing a new recombinantproduct, rVIIa-FP, which has a longer half-life than the only fac-tor rVIIa product currently on the market: Novo Nordisk’sNovoSeven®RT. A product with a longer half-life means thatpatients would need fewer doses of factor to stop bleeds, and thedoses could be spread farther apart. Inspiration Biopharmaceuti-cals is also working on a recombinant factor VIIa, which is nowin preclinical trials (not yet tested in humans).Novo Nordisk is in phase III clinical trial of a faster-acting

rVIIa product. It’s designed to produce a stronger clot so ableed can be stopped with fewer infusions.

Wishes for... New types of productsHow about a brand-new type of product—one that hasn’tbeen on the market yet? Maybe one that works in an entirelydifferent way from the products that are now available?“I would like to see a new product that would be more

Jo Schaffel

sponsored byNovo Nordisk Inc.

inhibitor insights


Wishful Thinking from Inhibitor Families

page 18


When gene therapy was firstproposed as a treatment forhemophilia, it sounded just

like science fiction. We had to use ourimaginations to understand this inno-vative technique because it was so dif-ferent from today’s standards oftreatment with factor concentrates.But science fiction can be used

as an inspiration for learning in theclassroom, just as teacher HarryClement Stubbs (1922–2003) did with his students. Stubbs taught highschool science for 40 years at MiltonAcademy in Milton, Massachusetts,and used science fiction as a teachingtool to motivate his students. Before his teaching career began,

Stubbs had trained as an astronomerat Harvard University, and then hadflown combat missions in a bomberduring World War II. But what his students may not have known abouttheir teacher was that he was also awriter of science fiction. Stubbs consid-ered himself a teacher more than awriter, and he used the pseudonymHal Clement when he wrote hard sci-ence fiction, a genre grounded in scien-tific principles. He wrote over 40 shortstories and 12 novels, always with ascientific basis. Even in his fiction,Stubbs wanted to be a teacher and pro-vide factual material for readers.In The Best of Hal Clement, editor

Lester del Ray collected 10 ofClement’s science fiction stories. Oneof these, “A Question of Guilt,” origi-nally published in 1976, included acharacter with hemophilia. The story

takes place sometime around the sec-ond century AD. Marc of Bistrita, adiplomat living near the Adriatic, trav-els to Rome to seek the advice of heal-ers, even Galen of Pergamum (not a fictional character, but arenowned Greek physician who livedin what is now Turkey). Marc’s foursons have been cursed with bleedingthat does not stop, and three havealready died. His remaining son,Kyros, a young boy of six, bruises easily and shows some lameness.To stop his son’s bleeding finger

cut, Marc applies his own blood, yethe believes that a better treatmentwould be to replace Kyros’s lost blood:possibly, he thinks, Kyros should drinksome blood, or perhaps new bloodcould be put directly into his veins.Then, after Kyros suffers a right biceppuncture wound from a sharp stick,Marc attempts a blood transfusion.Unfortunately, Kyros dies. His mother,unable to bear the grief of losing foursons to bleeding, commits suicide.In the afterword to del Ray’s volume,

Stubbs explains that “A Question ofGuilt” was originally written for ananthology of vampire stories that wasnever published; the story was subse-quently published in an anthology ofhorror stories, even though Stubbsconsidered it science fiction. The char-acter Marc was never identified as avampire in the story, though there wereallusions to his strange late-night behav-ior in search of blood from local villagers.As a memorial to author Hal

Clement, accolades from 26 notable

science fiction writers have been col-lected by Shane Tourtellotte in thebook Hal’s Worlds. In an interview,Stubbs comments, “I wrote the story,and when it was done it was hard sci-ence fiction. My vampire was a retiredRoman army surgeon of about thetime of Galen, who had the misfortuneto sire four [hemophilic] sons, ofwhom one was still alive at the time ofthe story. He got his unpopular reputa-tion with the neighbors by his attemptsto solve the problem of blood transfu-sion a couple of thousand years beforewe knew enough to have any chanceof doing so.” Regrettably, Stubbs’sstory contains some medical misinfor-mation: Marc identifies arteries andveins that are needed for the continu-ous circulation of blood within thebody; but in the second century, theGalen theory of blood flow was onlyone-way from the stomach, where foodwas converted to blood, and then to theheart where it was burned for energy.Other science fiction writers have

admired Hal Clement for the highquality of his writing and for his roleas their mentor. And I suspect that thestudents at Milton Academy admiredtheir teacher, Harry Stubbs, because theybenefited from his style of science teach-ing—augmented with science fiction.Don’t we all wish that our high

school science teachers had been asinnovative as Stubbs in capturing ourattention and stimulating our curios-ity? Today, we can also appreciate HalClement for including a character withhemophilia in a sci-fi short story.

Richard J. Atwood

richard’s reviewAnn Woodruff

Hemophilia in Science FictionThe Best ofHal ClementEdited by Lester del Ray (1979)

Hal’s Worlds: Stories and Essays in Memory of Hal ClementEdited by Shane Tourtellotte (2005)


Kathryn Ondek

Aloha Pulse on the Road!

Participants listen att

entively to Pulse on t

he Road speakers

Pulse on the Road speakers (left to right) Laurie Kelley, Michelle Rice,

and Jim Romano, along with Jennifer Chun of Hawaii Hemophilia

Foundation and Elizabeth Stoltz of Baxter Healthcare

Pulse on the Road kicked off2012 with a visit to Hawaii, during the same week that

the Supreme Court listened to oralarguments over the Affordable Care Act (ACA). Pulse on the Road welcomed 35

families of the newly founded HawaiiHemophilia Foundation, headed byJennifer Chun. Jenn is the mother offive, including two sons with hemo-philia. She’s done a super job of bring-ing the community together to learn,support one another, and network.

Pulse on the Road’s three-hourinsurance symposium began with Laurie Kelley’s look at the history ofhemophilia healthcare; how the UShealthcare system has treated us inthe post–HIV era; and how and whythat system has sometimes createdroadblocks that prevent access tocare. Next, Michelle Rice, director ofpublic policy at National HemophiliaFoundation, shared ideas on compar-ing and contrasting healthcare planswith an insurer, using the NHFInsurance Toolkit. Jim Romano ofPatient Services Inc. (PSI) concluded

by reviewing ACA and discussingwhat Hawaii can expect from healthcarereform. We had great audience interac-tion with a very informal atmosphere. Keep an eye on the news in June

for the Supreme Court’s decision onthe individual mandate and ACA. The court’s decision will affect us allfor a long time to come.Next stop…Hemophilia of North

Carolina! To find out more aboutPulse on the Road and where we areheaded this year, visit our website:

www.kelleycom.com

We are grateful to Baxter Healthcare for supportingthis event and all the Pulse on the Road symposia.


Why the Burst in NewProducts?It’s no coincidence that every manufac-turer of factor concentrates has one oreven several new products in thepipeline. This is because the patents ororphan drug “periods of exclusivity”1

on most current factor concentrateshave expired or will soon expire. Patentsand periods of exclusivity protect amanufacturer from competition, so thatafter investing time and research intocreating a product, the company hastime to recoup its expenses.

Within the last five years, thepatents, patent extensions, and periodsof exclusivity expired on all majorbrands of factor VIII, IX, and VII soldin the US. As less expensive genericforms, called biosimilars or follow-onbiologics, come to market, the loss ofthese patents and manufacturer protections will cut into pharma profits.As a result, pharma is looking for new,

improved products to patent and sell tomaintain market share and profits.

BiosimilarsAlmost all the major manufacturers of current factor products (US-basedand international) have one or morebiosimilar products in phase II or IIIclinical trials (see sidebar, page 13).Biosimilars are undergoing full clinicaltrials because, unlike generic forms ofchemical compounds that are easilyreproduced and cheap to make, bio-logic drugs such as clotting factor can’tbe made identical to the original forms.

The proteins in every brand of factorare slightly different. This is becausedozens of variables in the manufactur-ing process can alter a protein; a tinychange in the manufacturing process of a biosimilar might make it moreimmunogenic or less effective. That’svery important for hemophilia patients—more immunogenic means more likelyto produce an immune response andcause inhibitors to form.

Rest assured for now that the USFood and Drug Administration (FDA)will not rush, or fast-track, approvals ofbiosimilar factor. Several organizations,including NHF and Plasma ProteinTherapeutics Association (PPTA),have urged the FDA not to take short-cuts in approving biosimilars, fearingthat they would be less effective ormore immunogenic.2 Under theFDA’s current proposal, issued inFebruary, the extent of the clinicalwork needed for biosimilars to go to market will be determined case-by-case, and researchers believe that forfactor products, this will mean fullclinical trials.

And what about price? Biosimilarfactor will definitely be less expensive,but perhaps not by as much as manyof us would like. Unlike chemicalgeneric drugs (such as ibuprofen) thatmay sell for a fraction of the cost of thebrand-name drug (such as Motrin®),biosimilars are expected to sell at only10% to 30% less than current factorconcentrates. This is because manu-facturers will still have to recouptheir investments in research anddevelopment and build additionalproduction facilities, which cost $400to $500 million each.

Besides biosimilars, what else is onthe horizon? A lot.

Hemophilia Renaissance... from cover

generic refers only to chemical drugs, like pills and creams.

biosimilar refers to biologicdrugs, which are made fromliving organisms, or to theirproducts, such as vaccines or factor.

immunogenic – likely to produce an immune response

low immunogenicity –unlikely to produce animmune response (read:lower risk of inhibitors!)

1. A pharmaceutical company can apply for orphan drug status from the FDA for drugs with a potential target population of fewer than 200,000. Orphan drugs are granted a seven-yearperiod of exclusivity, during which the FDA will not accept applications for other similar drugs. 2. NHF letter to FDA on biosimilars:www.hemophilia.org/NHFWeb/Resource/StaticPages/menu0/menu7/menu122/NHF_FDABiosimilars.pdf. PPTA White Paper on Biosimilars:www.pptaglobal.org/UserFiles/file/White%20Paper-toPPTA6-4-09-withoutPlasSD.pdf.


Extended Half-LifeExtending the half-life of factor concentrates is by far themost intensive area of research—probably because it’s themost easily obtainable goal, with the highest potential toquickly generate new products.

The half-life is the amount of time it takes for one-half ofa drug to be removed from the blood. The half-life of factorvaries with each product, and also from person to person.For patients with inhibitors, the half-life of factor is short—sometimes measured in minutes instead of hours. For factorVIII deficiency without inhibitors, the half-life is about 8 to12 hours. For factor IX, it’s about 18 to 24 hours.

Factor with a longer half-life would offer obvious benefits:fewer infusions, fewer bleeds, lower lifetime cost, and betterquality of life. Imagine having to infuse only once every fiveor seven days for prophylaxis!

So how are researchers making factor with longer half-lives? They’re taking some different approaches, which we’ll review in the next few sections.

PEGylation

PEG stands for the chemical compound polyethylene glycol.PEGylation is the process of attaching long strands of PEGto the factor molecule. Researchers think that the constantlymoving, long strands of PEG whip around the factor mole-cule—keeping away immune cells, antibodies, enzymes, andanything that might attach to the factor and remove it fromthe blood. This same mechanism might also potentiallyreduce the formation of inhibitors or reduce the clearance(removal from the bloodstream) of the factor in the presenceof inhibitors.3 Early tests with PEGylation found that it didindeed lengthen the half-life, but it also destroyed up to 70%of the factor’s activity. To avoid this problem, subsequentresearch has focused on targeting where the PEG attaches tothe factor molecule. By finding the right spots, researchershave discovered that the PEGylated factor VIII still works,and its half-life can be at least doubled in animals. Results ofa clinical trial with PEGylated factor VIII in humans isexpected to be available this summer.

GlycoPEGylation

A variation of PEGylation is glycoPEGylation, in which PEG isattached to a sugar (glycan) that is attached to the factor. This

technique has successfully extended the half-life while stillmaintaining the activity of the factor.

PEG is Popular!Bayer is working on a PEGylated recombinant factor VIII (rFVIII) product,Novo Nordisk has a glycoPEGylatedrFVIII and rFIX molecule, and Baxter is testing a PEGylated rFVIII product, all in early-to-midstage testing in humans.

Polysialylation

A similar, but perhaps safer, alternative to PEGylation ispolysialylation. Instead of using PEG, this method usespolysialic acids, natural compounds found mainly on the

Although PEGylation has been

used successfully in several drugs

for short-term treatment, a problem

for hemophilia and chronic therapy

is the possibility that PEG could

build up to toxic levels over time.

Other PEGylated drugs use smaller

chains of PEG that can be partially

metabolized (broken down) and

excreted through the kidney. But

PEGylated factor uses long chains

of PEG; these are not naturally

metabolized and are too large to be

excreted by the kidney. Because

the liver is believed to be the primary

site where factor is removed from

the bloodstream, the long chains

of PEG attached to PEGylated

factor might build up over time in

the liver, even to toxic levels over

a patient’s lifetime.

PEGylation – modifying a molecule by attachingto it long strands of polyethylene glycol, todelay the molecule’s removal from the blood.

3. On the other hand, patients have made antibodies against PEGylated drugs used to treat other conditions.

PEG

Prob

lem

s?


surfaces of nerve cells and easilymetabolized. Not only do thesemolecules increase the half-life of the factor, but they’re also non-immunogenic, they reduce theimmunogenicity of the factor (making inhibitors less likely), andthey’re easily degraded, even atlarge doses. Baxter is in the earlystages of testing a polysialic acidrFVIII product in animals.

Fusion Technology

If you subscribe to HemAware or havevisited the exhibition hall at an NHFmeeting in the past few years, youmay have already heard about fusiontechnology. Fusion involves produc-ing a recombinant factor moleculethat has another recombinant moleculeattached—fused—to it. The fusedmolecule extends the half-life of thefactor. When in production, both thefactor and the fused molecule areexpressed by the cell line together asa unit, the same way as recombinantfactor is now produced. Two fusionprotein prospects are in clinical trials:albumin fusion and Fc fusion.

Albumin Fusion

Albumin is a natural blood plasmaprotein with a low immunogenicityand a long half-life of about 20 days.One of its jobs is to ferry smallermolecules through the circulatory

system. Attaching albumin to factorIX might help extend half-life asalbumin ferries the factor. To main-tain the factor’s activity, the albumin-fusion factor molecule was designedso that when the factor IX is activated(ready to participate in the clottingprocess), the albumin will break off—so it won’t interfere with the factor’sfunction. Early tests of a factor IXalbumin fusion molecule by CSLBehring have been shown to triple thehalf-life of factor IX. Just think: thiscould allow prophylaxis with once-a-week infusions. This same technol-ogy is also being used in a factorVIIa albumin-fusion product thathas recently entered clinical trials.

Fc Fusion

Biogen Idec has two fusion productsin clinical trials: a recombinant factorVIII and recombinant factor IX.Both use a “recycling” process toextend half-life. Here’s how it works:circulating proteins, including factor,are continually being cleared(removed) from the bloodstream.This happens naturally: one clear-ance process involves endothelial

cells, which line the insides of bloodvessels. These cells randomly latchonto proteins—such as factor—circu-lating in the blood, and then pullthem into the cell, where they aredigested by enzymes. The body seesthe older proteins as “trash” and effi-ciently removes them, allowing“fresh” proteins to be synthesized.

If we could somehow preventfactor from being digested by theendothelial cells, then it wouldremain in the bloodstream longer and have a longer half-life. This isthe goal of Fc fusion. Scientistshave found that some proteins, like certain antibodies produced by the immune system calledimmunoglobulin G (IgG), have a protein fragment called Fc attachedto them that protects them frombeing digested. When factor with Fc fused to it is pulled in by theendothelial cells, the cells “spit” thefactor back out into the bloodstream—recycling the protein! Biogen Idec’sclinical trials show an almost-doubledhalf-life for factor VIII and a near-tripled half-life for factor IX usingFc fusion.

cell line — a group of cells, maintained outside the body, used to produce recombinant proteins

expression — the process acell uses to take informationcoded in the DNA and thenmake a finished product,such as clotting factor


XTENylation

A third type of fusion molecule is XTEN. XTENs are long chains of proteins that act similarly to the chemical compound PEG. XTENylation is the fusion of XTEN to proteins, such as factor VIII or IX, to extend their half-life. XTEN fusion has several advantages over PEGylation: unlike PEG, XTEN is readily biodegradable and has little or no immunogenicity,and proteins attached to XTEN maintain their activity.Plus, compared to PEGylation, the manufacturing process is simpler and up to 50% less expensive. Amunix, the company that invented the XTENylation process, is partnering with Biogen Idec to develop XTENylated factors VII, VIII, and IX. Early studies of XTENylatedfactor are promising: an increase in the half-life of 1.6 times for factor VIII, 2.7 times for factor IX, and 7.6 times for factor VII, all in animals.

What does “1.6 times the half-life” mean, in practical terms? If the half-life of factor VIII is 12 hours,and if a new product shows an increaseof 1.6 times the half-life, the factorproduct would now have a half-life of19.2 hours. That’s pretty good. For afactor IX product showing an increaseof 2.7 times the half-life, the half-lifewould now be up to 65 hours—that’sreally good! So before you get tooexcited when you hear about anincrease in half-life, be sure to do themath: multiply the increase by the original half-life to see how many more hours or days the new product’seffectiveness is extended.

Enhanced Clotting Factors What if scientists could make factor work better, or faster?We could stop bleeds using less factor, or stop bleeds faster.

Faster-Acting Factor

Several faster-acting products are now in development.Novo Nordisk has bioengineered factor VIIa to make itfaster acting when compared with the company’s ownNovoSeven®RT recombinant factor VIIa—and with strongerclot formation. This means that a person with inhibitorscould control bleeds faster and with fewer infusions. Infact, the company hopes the product will initiate clotting aseffectively as an infusion of factor VIII or IX in someonewithout inhibitors. And because the clots are stronger,there may be less re-bleeding in the days after a bleed.Novo Nordisk initiated the phase III clinical trial of thisfast-acting recombinant factor VIIa in summer 2011.Bayer is developing a bioengineered recombinant factorVIIa that is faster acting and longer lasting, and hasrecently finished an early clinical study.

Hyperfunctional Factor

In 2009 the New England Journal of Medicine reported on a23-year-old man in Padua, Italy, who was diagnosed withthrombophilia (the tendency to form clots) as a result of amutated factor IX gene. Although the man had normal levelsof factor IX, his factor activity was eight times that of normalfactor IX! This mutation, dubbed factor IX Padua, has sincebeen cloned, and through bioengineering, several variants of


factor IX have been developed withhigh activity. These “hyperfunc-tional” factor IX variants will be use-ful not only in gene therapy and intreating factor IX deficiency, but alsoin treating factor VIII deficiency withinhibitors. When researchers testeddifferent hyperfunctional factor IXvariants, they found that high activitycould initiate clotting even in theabsence of factor VIII! These are notyet in clinical testing, and as the prod-ucts enter the trials, scientists willneed to watch carefully for too muchclotting, as happens with the naturalPadua mutation.

Tweaking the Clotting CascadeResearch on hemophilia treatmentisn’t limited to developing better clot-ting factors; it also includes modify-ing how coagulation worksinternally—so that treatment won’trequire infusing factor at all!

There are natural checks on coag-ulation. It works something like this:any injury to a blood vessel instantlyactivates the clotting cascade to begin

clot formation and stop blood loss. Atthe same time, the body kicks intogear to limit coagulation. Why? So theprocess won’t spiral out of controland cause excessive clotting (throm-bosis). One coagulation check is tissue factor pathway inhibitor, or TFPI.TFPI is a protein that slows or stopsfactor VII from combining with tissuefactor. When factor VII and tissuefactor combine, they activate factorsIX and X, making them ready to par-ticipate in the clotting cascade. Whenthe action of TFPI is blocked, morefactor IX and X are activated,increasing clotting. Researchers havefound that if TFPI is blocked, thencoagulation can proceed—even if theperson is missing factor VIII or IX,or has inhibitors!

Two anti-TFPI products are nowin early clinical development. NovoNordisk has developed a monoclonalantibody that blocks the action ofTFPI. This product can be infusedsubcutaneously (under the skin) andis in phase I clinical trial. The specifictarget population (hemophilia A orB, with or without inhibitors) has yetto be determined. Baxter is studying

another anti-TFPI compoundderived from brown algae, whichcan be injected subcutaneously ortaken orally.

Human Cell Culture LinesYou may know that recombinant clot-ting factors are produced from geneti-cally engineered baby hamster kidney(BHK) cells or Chinese hamsterovary (CHO) cell lines containing thehuman gene for factor VIII or IX.These animal cells produce (express)human factor, which is then collected,purified, freeze-dried, and bottled.But human factor VIII is a very largeand complex molecule that is hard forthese nonhuman cells to express.Although the BHK and CHO cell linesdo a good job of expressing factor, it’shard for nonhuman cells to properly“finish” the factor—meaning they maynot properly fold the factor into itsfinal three-dimensional shape, andthey may not do a good job of attach-ing other molecules to the factor’ssurface, as human cells do. Improp-erly finished proteins may not workefficiently or may have increasedimmunogenicity. On the other hand,if we used human cells to express andfinish factor proteins, then the cellsmay be able to express more factor,and that factor may have lowerimmunogenicity and may work better. But we’ll have to wait for the results of clinical trials to find out if this is true. Octapharma has an rFVIII product created by a human cell line currently inphase III clinical trial.

Custom-Designed Clotting FactorsNot all factor VIII or IX moleculesare identical. Factor differs slightlyamong different human races. Thismay be why African Americans havea significantly higher rate of


inhibitors: commercial factor may differ slightly from theirown factor, making it more immunogenic to them. Bioengi-neering of the factor molecule may allow for more custom-designed factor for specific populations, reducing theincidence of inhibitors.

Recombinant Porcine Factor VIIIInspiration Biopharmaceuticals is currently in phase III clini-cal trial of OBI-1, a new recombinant porcine (pig) factorVIII to treat acquired hemophilia A (an autoimmune disease)and hemophilia A with inhibitors. Porcine factor VIII is dif-ferent enough from human factor VIII that it usually escapesdetection by the immune system (so inhibitors aren’t alerted),but similar enough that it functions to produce a clot.

Besides the drugs and treatments mentioned here, lots of others are being explored. Read the Headlines section in PEN, and subscribe to the electronic NHF eNotesand HemAware Express for news releases on new treatmentsunder development.

What Happened to Gene Therapy?After raising more than $9 million during a decade offundraising for research into gene therapy, NHF’s “It’s Timefor a Cure” campaign ended in 2008. Yet many people arestill asking: Where’s the cure?

When the NHF campaign was implemented in 1998, ourcommunity was optimistic about the future of gene therapy—in hindsight, we were also naïve about the challenges. Genetherapy was slowed by setbacks: in 1999, 18-year-old JesseGelsinger, who suffered from a rare metabolic disorder, diedafter a gene therapy treatment at the University of Pennsyl-vania. Fearing safety issues and liabilities, researchers putmany gene therapy trials on hold after Jesse’s death—somefor years—while research protocols were reviewed and patientsafeguards strengthened. A few years later, four gene therapytrials were put on hold when a three-year-old boy in France,after having been cured by gene therapy of a fatal immunedeficiency disease (“Bubble Boy” disease), developed a can-cer similar to leukemia—and his gene therapy treatmentswere blamed. Within several years, two more boys in thesame clinical trial developed the same type of cancer, and in2007, a woman died after receiving a gene therapy treatmentfor rheumatoid arthritis.4 All these incidents occurred in con-ditions other than hemophilia, using different genes and dif-ferent viruses to carry the gene into the body than thoseused in hemophilia gene therapy.

Despite these setbacks, gene therapy has made steadyprogress since the first trial in 1989. Scientists worldwide areworking on individual pieces of the gene therapy puzzle thatcan eventually be assembled into effective treatments for avariety of diseases, from hemophilia to severe combinedimmune deficiency.

4. She was later found to have a systemic fungal infection, and the gene therapy treat-ment is believed to have weakened or stressed her immune system, letting the fungalinfection rage unchecked.

Patient Services Inc. is a national nonprofitorganization committed to providing a varietyof services to patients living with specific

chronic illnesses. Call or visit us online todayto see if you are eligible for assistance!

Some scientists are working onmore effective ways to get the genesfor producing factor into the cell ofchoice. Because viruses are experts atgetting genetic material into cells,most of this avenue of researchfocuses on bioengineering viruses toeffectively carry the genes to the cell.These bioengineered viruses, calledviral vectors, are disabled and can nolonger cause disease. They aredesigned to target only the cells ofinterest (for hemophilia, mainly livercells), to make them less immuno-genic, safer, and less toxic.

Other scientists are working onnon-viral vectors, including stem celltransplants that would then producefunctional factor. Still others are work-ing on how to target exactly where inthe DNA a gene will be inserted—reducing or eliminating the risk ofcausing cancer that can occur whengenes are randomly inserted into theDNA (which is what happened in ear-lier gene therapy trials). And scientistsare also working on bioengineeringthe genes for factor VIII and IX tomake it easier for a cell to producethem, and to make variations of thefactor proteins with higher activity—soless factor can do the job.

Scientists who attended NHF’sNovel Technologies and Gene Trans-fer for Hemophilia workshop believethat the technical details of an effec-tive gene therapy for hemophilia canbe worked out within the next five toeight years. Yet they don’t believethat gene therapy will be commer-cially ready until at least a decadefrom now. Why? Because no onegroup (research lab or pharmaceuticalcompany) will hold all the cards toput together an effective gene therapytreatment. The work of many differ-ent groups will need to be combinedto create safe, effective products thatcan be marketed. The problem is thateach group has patented its own pro-

prietary processes, techniques, andbioengineered molecules. Unlesssome pharmaceutical company withdeep pockets can buy out or make anarrangement with each group thatholds a patent, we’ll just have to waituntil the patents expire—and most willexpire in about a decade.

When gene therapy does becomea reality, you’ll most likely see a treat-

ment for factor IX deficiency debutfirst. Why? Because the gene for fac-tor VIII is so large that it’s hard topackage the gene and other necessarygenetic material into some viral vec-tors. The factor VIII protein itself islarge too, and difficult for some cellsto produce. The factor IX proteinand its gene are much smaller, mak-ing them easier to work with.


The FDA requires that new drugs and treatments be tested for safety,and also to demonstrate that they effectively treat the disorder ordisease for which they are being developed. Drugs always start with aphase I clinical trial, and then may move to phase II and phase III trials.If a drug is found unsafe or ineffective at any stage, then the clinicaltrial will be ended, and research on the drug will be either modifiedor abandoned.

Phase I: After a new drug or treatment is initially tested on animals,researchers test it on a small group of people (20–80) to evaluate safety,determine the safe dosage range, and identify side effects.

Phase II: If a drug or treatment appears safe at the end of the phase Itrial, researchers give it to a larger group of people (100–300) to evaluateits effectiveness in patients, and to further assess safety.

Phase III: At this stage, the drug or treatment is given to an even largergroup of people (1,000–3,000) to confirm effectiveness over a broadrange of patients, monitor side effects, compare to commonly usedtreatments, and collect information to promote safe use. For raredisorders such as hemophilia, it’s almost impossible to enroll 1,000patients for a clinical trial. In these cases, the FDA will approvephase II or III trials with much smaller populations.

Phase IV: Post-marketing studies provide more information, includingthe drug or treatment’s risks, benefits, and best use.

For information: clinicaltrials.gov/ct2/info/understand

Clinical Trial Phases


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One factor IX gene therapy treatment has shown somepromising early clinical results, as published in the New EnglandJournal of Medicine in December 2011. Although the treatmentcaused some mild liver toxicity (which was managed), four ofthe six patients in the study are now using much less factor orno factor after more than a year, with factor levels after thetreatment ranging from 2% to 12%. Although none of the sixpatients’ factor levels reached 13%—the minimum factor levelneeded to stop most spontaneous joint bleeds, and the mini-mum goal of gene therapy—the study showed that the tech-nique could work. More clinical studies are underway usingthis technology. But because factor VIII is a much larger molecule, it may not work using this same system.5 Scientistsare confident that hemophilia will be cured by gene therapy, butit will take longer than we anticipated. The good news is thatjust as the Renaissance ushered in a new era of rapid scientificexploration and innovation following the Middle Ages, we arenow in a Renaissance of hemophilia product development.Fortunately, we can expect advanced products in the near futurethat will greatly improve our quality of life.

5. One drawback of enrolling in early gene therapy clinical trials is that you won’t be ableto enroll in another trial—of the “new and improved” version of the therapy—using thesame vector because your immune system is now trained to rapidly destroy the viral vec-tor the next time it’s encountered.

Know as much as possible about the clinical trial,and feel comfortable asking your healthcare teamabout it. Use these questions as a guide:

• What is the purpose of the trial?

• Who is going to be in the trial?

• Why do researchers believe the experimentaltreatment being tested may be effective?

• Has this treatment been tested before?

• What kinds of tests and experimental treat-ments are involved?

• How do the possible risks, side effects, andbenefits in the trial compare with my currenttreatment?

• How might this trial affect my daily life?

• How long will the trial last?

• Will hospitalization be required?

• Who will pay for the experimental treatment?

• Will I be reimbursed for other expenses?

• What type of long-term follow-up care is partof this trial?

• How will I know that the experimental treat-ment is working? Will results of the trial begiven to me?

• What happens if I am harmed by the trial?

• Who will be in charge of my care?

Adapted from clinicaltrials.gov/ct2/info/understand

Questions to ask before participating in a clinical trial


headlinesnonprofit

Wheels for the World On June 17, cyclist Barry Haarde will launch a coast-to-coast 3,667-mile bike ridefrom Oregon to New Hampshire to raise funds for the international nonprofit SaveOne Life. Barry is a 46-year-old Texan living successfully with hemophilia A, HIVand hepatitis. This is the first time someone will bike across America for hemophilia.Why this matters: The ride will publicize hemophilia, show what people with hemo-philia can do, and raise funds for those who are without treatment.For info: www.SaveOneLife.net

The Time is NOW for VWD Patients Arizona Hemophilia Association (AHA) hosted the firstannual National Outreach for von Willebrand (NOW)conference. AHA executive director Cindy Komar and herteam assembled a great cast of speakers and facilitators,and provided entertainment for the kids during the weekendevent. At least 25 states were represented. NOW wasfunded by CSL Behring, makers of Humate-P® for VWD.Why this matters: Although up to 1% to 2% of Americansare affected by VWD, most patients remain undiagnosedor are not connected with HTCs.For info: www.hemophiliaaz.org

NHF Inhibitor Education Summits July 19–22 • Miami, Florida

August 2–5 • San Diego, California

Join inhibitor families and patients for a special gathering tolearn about treatments and to network. Summits are forinhibitor patients only; travel and accommodations provided.Why this matters:With only about 1,200 patients withinhibitors in the US, families often feel isolated, and can gainsupport by meeting each other.For info: Zuiho Taniguchi, [email protected]

AHA executive director Cindy Komar (far right) with CSL Behringsupporters of NOW

Laurie Kelley


manufacturer

Bayer HealthCare’s Factor Solutions program now providesthe Bayer Reimbursement Helpline to assist Kogenate® FSusers with the changes in healthcare reform and insurance,including product reimbursement and claim issues; assessingnew insurance and alternate funding sources; understandingExplanation of Benefits; and determining eligibility forassistance programs. Why this matters: Some insurancechanges may be specific to the brand of factor you use.For info: 800-288-8374The Bayer Reimbursement Helpline does not guarantee reimbursement.

Factor Solutions Program

Baxter now has a 2 mL diluent volume forAdvate, available for dosage strengths 250,500, 1000, and 1500 IU. The new packageincludes a 25-gauge Terumo butterfly infusionset to help accommodate the smaller infusionvolume. Advate will continue to be availablewith a 5 mL diluent for dosage strengths 2000IU and 3000 IU. Why this matters: Smallerdiluent size means smaller volume andpotentially faster infusions. For info: www.thereforyou.com

Advate’s New Diluent SizeKedrion Biopharma is continuingthe Koate®-DVI TRY IT programthrough December 31, 2012.Koate-DVI is a plasma-derivedfactor VIII concentrate that issubject to double-viral inactivationwith solvent detergent and heatedin the final container to 80⁰ C. TRY IT provides up to twoweeks’ therapy at no charge forqualified applicants. Applicants

must be factor VIII patients whohave never used Koate-DVI, whohave physician approval, andwhose request does not exceed50,000 IU. Why this matters:Hemophilia patients tend to bebrand loyal; free trials offer a wayto sample new products withoutcommitment.For info: www.koate-dviusa.com

Try Koate-DVI

global

Inhibitors: Independent Iran Iran has launched domesticproduction of a recombinantfactor VIIa concentrate to treat hemophilia patientswith inhibitors. The product will be manufactured at theAryogen Research and Manufacturing complex, whichreportedly has also initiated production of recombinantmonoclonal antibodies. Currently, Iran imports NovoNordisk’s NovoSeven®RT. Why this matters: Iraniangovernment officials estimate that producing both factorVIIa and monoclonal antibody products will save thecountry approximately $100 million annually.Source: IBPN, www.marketingreserachbureau.com

Meet the World of HemophiliaWorld Federation of Hemophilia Biannual Congress

July 8–12, 2012Palais des Congrés de Paris

Paris, FranceOver 4,000 patients, healthcare providers, andindustry reps are expected at WFH’s biannual event.Why this matters: It’s important for the global community to meet to share new treatments, strategies,and networking opportunities to advance care aroundthe world.For info: [email protected] or www.viparis.com


featured by LA Kelley Communications, Inc.My First Factor series is designed to help young children, ages 18 months to 4 years, understand theirbleeding disorder.My First Factor: HTC Who does a toddler meet at the HTC? Help yourchild develop a positive relationship with his or herhemophilia treatment center. By Shannon Brush,mother of a son with hemophilia. Illustrated byBrooke Henson. Published October 2011 by LAKelley Communications, Inc. Sponsored by FactorSupport Network.To order: www.kelleycom.com

clarificationIn “Private Parts: Is Your PersonalHealth Information Exposed?” (February 2012), a reference to theHERO study may have given a misleading impression concerning itspatient privacy policy.HERO is the largest-ever, multina-

tional multi-method study exploring thepsychosocial impact of hemophilia. It issupported by Novo Nordisk and led bythe HERO International AdvisoryBoard. In each of 10 participating coun-tries, patients and caregivers wererecruited through hemophilia patientorganizations.Although the general privacy policies

of Kantar Health, the company carryingout the study, may not have beendescribed on the NHF web page thatinvited patients to participate, theHERO study actually took these extraprecautions to protect patients and caregivers:(1) Independent Research Board (IRB)overseeing conduct of the study bythe sponsor and recruitment effortsby NHF;

(2) IRB-approved patient recruitmentmaterials distributed by NHF thatinclude description of how the datawill and will not be used and plans to protect patient privacy;

(3) an additional IRB-approved descrip-tion of the risks/benefits of participa-tion and privacy protection on theonline survey itself, including amandatory consent; and

(4) a toll-free contact number and websitefor the IRB, and an email contactfor the HERO team at KantarHealth where potential participantscould direct questions.Any patient contact information

will be used solely by Kantar Health toprovide honorarium for participation,and personal information will not betransferred to any third parties.

medical

First Hand-Held Device Detects Need for CT ScansThe US FDA approved marketing of the first hand-held device,Infrascanner Model 1000, intended to aid in the detection ofintracranial hematomas. A trained healthcare provider can use thedevice to help determine the likelihood of an intracranial hematomaand the need for further diagnostic procedures, such as a computedtomography (CT) scan. Why this matters: An intracranialhematoma can be life-threatening if it is not treated immediately.For info: www.fda.gov or 888-INFO-FDA

http://www.medcitynews.com/wordpress/wp-content/uploads/Infrascanner-Model-1000.jpg

effective during an inhibitor [bleed]instead of taking so many days orweeks for a bleed to heal,” saysCazandra MacDonald, mother of twosons with inhibitors. Inspiration Biopharmaceuticals is

currently in the phase III clinical test-ing stage of a new recombinant porcine(pig) factor VIII, called OBI-1. It’snot a bypassing product but isintended to treat hemophilia A withinhibitors. Porcine factor VIII is closeenough to human factor VIII to par-ticipate in the coagulation process toform a clot, but different enough thatit escapes detection by most inhibitorsto human factor VIII. Novo Nordisk is also working

on a new treatment method calledAnti-TFPI, which is in phase I clini-cal trial. TFPI stands for tissue factorpathway inhibitor. It’s a protein thatstops or slows the formation of bloodclots. Anti-TFPI blocks the action ofTFPI, allowing coagulation to pro-ceed even in the absence of factorVIII or factor IX. And best of all, itcan be injected subcutaneously!The new or improved products

currently being tested hold muchpromise, but not everyone may bewilling or able to change treatmentregimens right away. Cazandraexplains, “There would have to be some significant reasons tochange...when you find a productthat works, why change?” Cicelywould keep an open mind aboutchanging her regimen. Debbiemight be willing to use a new orimproved product: “If there wasgood science behind it...if it offered

substantially better benefits and Ithought it was safe.”

Wishes for...Better access to careUnfortunately, many of the chal-lenges facing families with inhibitorsmay not be fixed by new andimproved products alone. Your family may live far from a

hospital or HTC, or the medical staffnear you may have little or no experi-ence with inhibitors. “We have to go toanother state to monitor the inhibitorbecause their doctors have inhibitorexperience,” Cazandra explains. Moretreatment centers with staff trained ininhibitors would ease this burden.The high cost of inhibitor products

is another major concern. As medicalcosts skyrocket, employers and insur-ance companies are taking a closerlook at their bottom line. Theymay start limiting access to certain(more expensive) products or dis-couraging the use of “newer” orwhat they consider “experimental”products. Employers may cut backon their employees’ insurance cov-erage. But, says Debbie, “It wouldsure be nice to have [products] thatmore people could have access to.”

Wishes for...Finally, a cure Of course, a cure for hemophiliaor prevention of inhibitors topseveryone’s list. Debbie explains,“Inhibitor patients have more joint

damage, more hospitalizations...Thetop of my wish list would be medicinesor therapies that cure hemophilia oreliminate the inhibitor.” As scientists continue to study the

complex genetics of hemophilia, theyhope to gain insights into who mightbe more likely to develop aninhibitor. We may be able to tailortreatments to prevent inhibitors inpeople who show a high risk of devel-oping them based on their genetics.Or, if inhibitors do develop, specifictreatments could be created for indi-viduals based on their particulargenetics or biochemistry.Researchers are working on finding

ways to cure or prevent hemophiliaaltogether. If we could replace thedefective genes that are causing hemo-philia with properly working genes,patients could eventually produce theirown clotting factor. No bleeds, noinhibitors. A wish come true.

CURE


As I See It... from p. 3

be by the truckload. I hope that when I share my story or a fewwords of encouragement, someone may see a positive in what’soften the negative of living with a chronic condition.Siblings can be like day and night. One is the life of the

party, and the other prefers a quiet corner. One is a sportsnut, and the other a musician. One is a math whiz, and theother a writer. I had no idea, when hemophilia came into mylife a second time, that this journey would be so incrediblydifferent from the first. Ten years after my older son wasborn, my younger son’s birth has become the biggest sur-prise and biggest challenge of my life.But day always follows night, and dawn brings hope.

Hope can be the best of things, and it never abandons you.

I am filled with hope that my sons will continue to thrivedespite their bleeding disorder. I am filled with hope that myhusband and I will gather the strength and knowledge weneed to continue managing Julian’s and Caeleb’s treatments.And I am filled with hope that one day, the light will revealitself and we will move into another, even better season whileliving with hemophilia.

Cazandra lives in Truth or Consequences, New Mexico, with herhusband, Joe, and their sons, Julian and Caeleb. She works in thehealthcare industry, is active in church ministry, and writes a columnfor the local newspaper. Follow more of her journey with hemophilia:

[email protected]

Inhibitor Insights... from p. 4


Inbox... from p. 2

Project SHARETHANK YOU SO

much for helpingReniel. We receivedthe factor in time tosave his life. In twoweeks he will have afollow-up checkupwith his doctor. Godbless, and thank youfor your sincerity inhelping us!

Raymund NañosBlood Brothers Aid, Inc.Philippines

THANK YOU FOR THE SUPPORT GIVEN TO

my son Jovan. I am so grateful for yourlove and care. It has not been easy for himfor the last three weeks because of thebleed, but thank God we have people likeyou in the world. Be blessed. Stella SsewunguUganda

THANK YOU SO MUCH FOR FULFILLING MY

request. I received the FEIBA yesterday.My mom got it from HAPLOS [a localhemophilia organization]. It came in timefor the bleed in my right hip. I was verylucky to have the medicine. Thank God Iwas able to infuse it yesterday. My heart-felt thanks to you. Robert Jhonn BunagPhilippines

I JUST RECEIVED YOUR GIFT TODAY. YOU’REreally very generous. I didn’t believe myeyes: three vials of factor, each more than1700 IU. These things I’d seen only in pictures on the Internet. From the deepestbottom of my heart, I appreciate you andyour organization. Thank you so muchfor bringing me such feelings. I hope youare always strong, healthy and happy togo forward on your compassionate way.Le Huu Hung Vietnam

“Private Parts: Is Your Personal HealthInformation Exposed?” I HAD A CHANCE TO PEEK AT THE

November issue of PEN and the privacy work you’ve done. Kudos—this is great work. Such an important topic to provide education and provokethoughtful dialog. We continue to communicate on this as well. Comingfrom multiple sources can only supportlearning for our community members! Kimberly HaugstadExecutive DirectorHemophilia Federation of America

A mother is a person who seeing there are only four pieces of pie for five people,promptly announces she never did care for pie.

—Tenneva Jordan

God could not be everywhere and therefore he made mothers. —Jewish proverb

Mother’s Day ParentingMoment

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Hemophilia Renaissance - Kelley Com Technologies and Gene Transfer for Hemophilia, held ... choco late ice cream, and embraces life with all his heart. They have a bond as brothers,