2017

Proven Clinical Experience

Laurie Kelley August 6, 2017
This is a paid public announcement from Shire and does not constitute an endorsement of products or services. When you click on the links in this blog entry, you will be directed to the ADVATE® [Antihemophilic Factor (Recombinant)] website. LA Kelley Communications always advises you to be a savvy consumer when contacting any company, do not reveal identifying information against your will.

Proven Clinical Experience

Prescription drug candidates today go through clinical trials and rigorous efficacy and safety testing but what does that mean for its use in the real world? What does that mean for you?

Clinical studies are very important for bringing products to market, and for expanding the indications for current products. At any given time there are a number of clinical studies happening in hemophilia with the goal of bringing you safe and efficacious drugs. Please read below about one drug and its clinical study results.

Indications

ADVATE is a medicine used to replace clotting factor (factor VIII or antihemophilic factor) that is missing in people with hemophilia A (also called “classic” hemophilia).
ADVATE is used to prevent and control bleeding in adults and children (0-16 years) with hemophilia A.
Your healthcare provider may give you ADVATE when you have surgery.
ADVATE can reduce the number of bleeding episodes in adults and children (0-16 years) when used regularly (prophylaxis).

ADVATE is not used to treat von Willebrand disease.

SELECTED IMPORTANT RISK INFORMATION

You should not use ADVATE if you:
• Are allergic to mice or hamsters.
• Are allergic to any ingredients in ADVATE.
Tell your healthcare provider if you are pregnant or breastfeeding because ADVATE may not be right for you.

Extensively Studied

ADVATE has been extensively studied, with results spanning over a decade.1-6

In one study it was shown that:
• 42% of patients experienced zero bleeds during one year on prophylaxis7
• prophylaxis with ADVATE improved physical health-related quality of life compared with on-demand treatment7*

*Clinically meaningful changes were not seen in the physical health-related sub-categories of General Health and Physical Functioning, and the mental health-related component score and sub-categories of Mental Health, Role Emotional, Social Functioning, and Vitality.

We’re proud that only ADVATE has 13 years of real-world experience as a third-generation plasma/albumin-free recombinant factor VIII and it has physical health-related quality-of-life results in the prescribing information for people with hemophilia A.7,8

SELECTED IMPORTANT RISK INFORMATION

Your body may form inhibitors to factor VIII. An inhibitor is part of the body’s normal defense system. If you form inhibitors, it may stop ADVATE from working properly. Consult with your healthcare provider to make sure you are carefully monitored with blood tests for the development of inhibitors to factor VIII.

Side effects that have been reported with ADVATE include: cough, headache, joint swelling/aching, sore throat, fever, itching, unusual taste, dizziness, hematoma, abdominal pain, hot flashes, swelling of legs, diarrhea, chills, runny nose/congestion, nausea/vomiting, sweating, and rash.
Tell your healthcare provider about any side effects that bother you or do not go away or if your bleeding does not stop after taking ADVATE.

Our Commitment

Shire is committed to advancing treatment and providing product support programs and services for patients like you. Learn more about our CoPay assistance program, free trial offer and so many other great resources to help you through your journey at ADVATE.com.†

†Eligibility requirements, restrictions and terms and conditions apply.

Please click here for ADVATE Indications and Detailed Important Information.

ADVATE [Antihemophilic Factor (Recombinant)] Important Information

Indications

ADVATE is a medicine used to replace clotting factor (factor VIII or antihemophilic factor) that is missing in people with hemophilia A (also called “classic” hemophilia).
ADVATE is used to prevent and control bleeding in adults and children (0-16 years) with hemophilia A.
Your healthcare provider may give you ADVATE when you have surgery.
ADVATE can reduce the number of bleeding episodes in adults and children (0-16 years) when used regularly (prophylaxis).

ADVATE is not used to treat von Willebrand disease.

DETAILED IMPORTANT RISK INFORMATION

You should not use ADVATE if you:
• Are allergic to mice or hamsters.
• Are allergic to any ingredients in ADVATE.
Tell your healthcare provider if you are pregnant or breastfeeding because ADVATE may not be right for you.

You should tell your healthcare provider if you:
• Have or have had any medical problems.
• Take any medicines, including prescription and non-prescription medicines, such as
over- the-counter medicines, supplements or herbal remedies.
• Have any allergies, including allergies to mice or hamsters.
• Have been told that you have inhibitors to factor VIII (because ADVATE may not
work for you).

Your body may form inhibitors to factor VIII. An inhibitor is part of the body’s normal defense system. If you form inhibitors, it may stop ADVATE from working properly. Consult with your healthcare provider to make sure you are carefully monitored with blood tests for the development of inhibitors to factor VIII.

You can have an allergic reaction to ADVATE.
Call your healthcare provider right away and stop treatment if you get a rash or hives, itching, tightness of the throat, chest pain or tightness, difficulty breathing, lightheadedness, dizziness, nausea or fainting.

Side effects that have been reported with ADVATE include: cough, headache, joint swelling/aching, sore throat, fever, itching, dizziness, hematoma, abdominal pain, hot flashes, swelling of legs, diarrhea, chills, runny nose/congestion, nausea/vomiting, sweating, and rash. Tell your healthcare provider about any side effects that bother you or do not go away or if your bleeding does not stop after taking ADVATE.

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.

Click here for ADVATE full Prescribing Information.

References:

1. Valentino LA, Mamonov V, Hellmann A, et al. A randomized comparison of two prophylaxis regimens and a paired comparison of on–demand and prophylaxis treatments in hemophilia A management [published correction appears in J Thromb Haemost. 2012;10(6):1204]. J Thromb Haemost. 2012;10(3):359–367.

2. Shapiro AD, Schoenig-Diesing C, Silvati-Fidell L, Wong WY, Romanov V. Integrated analysis of safety data from 12 clinical interventional studies of plasmaand albumin-free recombinant factor VIII (rAHF-PFM) in haemophilia A. Haemophilia. 2015;21(6):791–798.

3. Tarantino MD, Collins PW, Hay CR, et al, and the RAHF–PFM Clinical Study Group. Clinical evaluation of an advanced category antihaemophilic factor prepared using a plasma/albumin–free method: pharmacokinetics, efficacy, and safety in previously treated patients with haemophilia A. Haemophilia. 2004;10(5):428–437.

4. Négrier C, Shapiro A, Berntorp E, et al. Surgical evaluation of a recombinant factor VIII prepared using a plasma/albumin–free method: efficacy and safety of ADVATE in previously treated patients. Thromb Haemost. 2008;100(2):217–223.

5. Blanchette VS, Shapiro AD, Liesner RJ, et al, for the rAHF–PFM Clinical Study Group. Plasma
and albumin–free recombinant factor VIII: pharmacokinetics, efficacy and safety in previously treated pediatric patients. J Thromb Haemost. 2008;6(8):1319–1326.

6. Auerswald G, Thompson AA, Recht M, et al. Experience of Advate rAHF–PFM in previously untreated patients and minimally treated patients with haemophilia A. Thromb Haemost. 2012;107(6):1072–1082.

7. ADVATE Prescribing Information.

8. Grillberger L, Kreil TR, Nasr S, Reiter M. Emerging trends in plasma-free manufacturing of recombinant protein therapeutics expressed in mammalian cells. Biotechnol J. 2009;4(2):186–201.

© 2017 Shire US Inc., Lexington, MA 02421. All rights reserved. 1-800-828-2088.
SHIRE and the Shire Logo are registered trademarks of Shire Pharmaceutical Holdings Ireland Limited or its affiliates.
ADVATE is a trademark or registered trademark of Baxalta Incorporated, a wholly owned, indirect subsidiary of Shire plc.
All other product brands or trademarks appearing herein are the property of their respective owners

S32465 07/17

Learning from (Near) Catastrophe

Laurie Kelley July 30, 2017

Americans learn from catastrophe,
and not from experience. Teddy Roosevelt

That’s a great quote by one of my favorite presidents; I feel like we have been having a bit of a healthcare catastrophe now in Washington DC. And it’s a great learning experience. Unfortunately, it comes with a steep price.
 
Back in 2010 we began warning the hemophilia community about coming changes in healthcare reimbursement through our event Pulse on the Road, and our newsletter Pulse. Insurers were balking at the high cost of treatment and care,
especially for those with chronic disorders like hemophilia. While for years insurers carefully sidestepped irritating and challenging the hemophilia community about prices of drugs—perhaps because of our tragic history with contaminated blood products—they began slowly applying the screws to what they would and would not cover . It shocked us then—how dare they? But nothing seems to shock us now, from the antics of the current administration to the all out assault on the
gains for those with chronic disorders through Obamacare.
 
Through Obamacare (formally, The Affordable Care Act [ACA]), our community finally enjoyed no lifetime limits, no annual limits, no discrimination through pre-existing conditions, and children would stay on their parents plan, married
or not, till age 26. Medicaid coverage was expanded in many states to include more people in need. We also warned that this came at a price, and this is where the conflict lies. Who will pay for all this? It’s like giving a teen a credit card with no limit. The spending has to stop somewhere and costs must be contained.
 
The Trump Administration introduced it own bill, to repeal Obamacare. The Better Care Reconciliation Act sought to unravel some of the gains, including rolling back the individual mandate (that each American must have insurance, with notable exceptions), shrinking the Medicaid expansion, offering massive tax cuts, and reducing federal funding. The Congressional Budget Office, which is bipartisan (meaning it doesn’t favor one party or another) calculated that 24
million Americans would be uninsured by 2026 if this bill passed. Premiums would drop to 20% lower but deductibles (out of your pocket) would increase. Insurers would no longer have to cover Essential Health Benefits. Why do some Republicans want it? It cuts $600 billion in taxes that help pay for Obamacare, which covered extended coverage costs through taxes on couples earning more than $250,000.
 
Senate Majority leader Mitch McConnell postponed this bill after the scathing assessment by the CBO. In one poll only 17% of voters approved it! And senators listened to their voters. In a nailbiting session, the Senate voted early Friday morning to block the “Skinny Repeal.” John McCain (R-AZ) stole the show by casting his vote “No,” which led to an audible gasp.
My friend Deena from Arizona, whose son has hemophilia and inhibitors, wrote on Facebook, “I heart John McCain! Thank
you Senator for doing what so many didn’t and thinking of your constituents! Once a hero… Always a hero! I’m so proud to be an Arizonan! Pre-existing conditions just got a post-existing boost!”
 
John McCain flew all the way to Washington DC to vote a mere two weeks after brain surgery for cancer. Stunning
dedication. Our community was thrilled overall, and so many rose to call, fax and tweet their senators not to vote for this bill. I saw NHF, HFA, and all the chapters rallying around one battle call, “Vote no!”
And it came to pass. We have a reprieve.
But it’s far from over. The House Republicans are angry with the Senate Republicans. The Trump administration seems at war with itself, firing appointees left and right. I hope Teddy Roosevelt was right that we learn from catastrophe, or near-catastrophe. We need to learn fast because there will be more skirmishes and battles, as we continue to fight to protect healthcare coverage for our loved ones with bleeding disorders.
 
Congress is on vacation now, and I am leaving today for Utah, to escape to the wilderness for a few days to visit my
daughter, who proudly works for the US Forestry Service, and away from news about the reality-TV drama that is Washington DC these days. Score one for us… for now.
 
Read more about what this means for bleeding disorders here: http://www.patientservicesinc.org/News/ArticleID/1149http://www.hemophiliafed.org/
https://www.hemophilia.org/

Ups and Downs of Theme Parks Rides

Laurie Kelley July 24, 2017

Summer is in full force and with it, trips to theme and amusement parks. I’m a huge lover of them, including the thrill rides, like roller coasters. In 2000-2002 there were many stories and studies in the news about the potential for brain bleeds, and these were about people without bleeding disorders. Last year came the first reported case of symptomatic bilateral subdural hematoma associated with riding a centrifugal motion simulator ride. 

What does this mean for our kids (and big kids–adults!) who love to ride roller coasters and simulator rides? Have you asked your hematologist for his or her opinion? I decided to rerun one of my favorite articles from PEN 2002 about risks for kids with hemophilia at theme parks, written by Dr. Richard Lipton.

Summer is here, and millions of families will seek adventure and thrills at theme parks like Six Flags, Disney World or Universal Studios. What a wonderful day a family can have at a theme park! Kids and parents love the rides, water slides, entertainment and general excitement. Are there any special safety concerns or precautions for families with a child with hemophilia? Yes!

Think of a theme park as a very big playground, but with an atmosphere favoring less parental control—a setting that can lead to impulsive behavior by children. Imagine yourself at a typical theme park. You’ll have general health concerns. Parks can be crowded, hot and sunny—so apply sunblock and drink plenty of water. Theme parks have paved surfaces, harder than public playgrounds, and filled with children running. Your child needs to wear appropriate footwear. Flip-flops or Texas might be suitable for water activities, but sneakers are safer for walking and running.

You’ll also have concerns specific to the theme park you visit. “Mind Eraser,” “Shockwave,” and “Nitro”—what about these special high-end rollercoaster rides? Riders are frequently subjected to changing speeds that result in “G-forces” similar to those experienced by trained, appropriately suited and restrained combat fighter pilots. Your child becomes “Top Gun” in shorts and a T-shirt! Parents should remember that any person can experience head trauma on these specialized rides.

How is the head affected by a ride like the Mind Eraser? Recall that your brain is surrounded by fluid; it is floating inside your skull. This arrangement cushions the brain, and reduces movement, protecting your brain from direct trauma and sudden shifts in skull position. It works quite well in our daily activities, and in automobiles (as long as we’re wearing a seatbeat). Now imagine speeding over the crest in a roller coaster. All of a sudden you’re weight- less, like an astronaut—this is called a Negative G- force. (You’ll have no trouble recognizing this moment, because every- body screams!) Then, after the coaster speeds down and resumes its climb, you feel your backside being pushed into the seat. It feels like the force of gravity has suddenly increased. This is a Positive G- force. Although your body is restrained, high G-forces could exceed the protective cushioning of fluid surrounding the brain, and could cause injury.

Interestingly, this year New Jersey became the first state to seek legal restrictions on the maximum allowable G-forces on amusement park rides. The regulations result from concerns raised by physicians about the association between neurologic damage and high G-forces on these rides. Certainly, such injuries occur very infrequently, but serve as a cautionary note to all riders of high-end roller coasters—with hemophilia, or without.

My advice? Take some precautions. Level the playing field by giving your child a prophylactic infusion of factor the morning of your visit to a theme park. Yesterday’s dose is not sufficient! Don’t wait until your child reports the symptoms of a bleed—it may be too late. Besides, your child is not going to report the flop he took running to the haunted house until you’re stuck in traffic on the long, long ride home.

Infuse first, then have a great time!

Dr. Richard Lipton was the physician in charge of the hemophilia treatment center at the Long Island Jewish Medical Center. As a United States Air Force Physician (1966–1968), Dr. Lipton knew several fighter pilots, who took him on “joy rides” (with lots of G-forces) that more than fulfilled his childhood fantasies. He is now retired.

 

 

Call of the Wild!!

Laurie Kelley July 16, 2017

With only five days and 250 miles to go, Barry Haarde is entering the final stretch of his Wheels for the World bike tour to raise funds for Save One Life.

Barry, an avid cyclist with hemophilia, is completing the last leg of a 1,000 mile trek on the Alaska Highway. At the 500-mile mark of his original 2,000 mile route, he collided with another cyclist (who ended up going home with a broken pelvis) and Barry has been showing his true grit through bumps, bruises, a very sore back and lots of factor infusions to stay the course. Given his accident, 1,000 miles alone will be a major achievement!

Dubbed “Call of the Wild,” this is Barry’s sixth long-distance bicycle tour. Call of the Wild started in Dawson Creek, British Columbia and is ending in Anchorage, Alaska. His first five tours totaled 19,000 miles and raised over $200,000 for Save One Life!

What’s remarkable about this achievement is that Barry has hemophilia, HIV and a contracted knee joint… health issues that would stop most people from considering this audacious ride. But Barry is not most people…he’s driven by memories of the brother and brother-in-law he lost to hemophilia and HIV, and all the friends in the community lost to HIV. In addition, he knows firsthand the pain suffered by those in developing countries who often lack access to blood-clotting medicine.

Save One Life is an international nonprofit that provides direct support for families with bleeding disorders in developing countries. Save One Life offers families individual sponsorships, college and vocational school scholarships, and micro-enterprise grants. I founded Save One Life in 2001 to engage families who have access to blood-clotting medicine and great medical care to assist families with bleeding disorders who need our help. Many survive on only $1 a day. Save One Life currently provides sponsorships to 1,323 individuals in 12 countries, through over 450 sponsors. Barry is one of them!

Only $3,000 more is needed to reach Barry’s fundraising goal of $35,000. Donate today at Save One Life. And consider sponsoring a child in need.

 

Thank you, Barry!

Follow Barry’s journey on Facebook here!

What Does Gene Therapy Mean to YOU?

Laurie Kelley July 9, 2017
Written by Laurie Kelley 
Originally published in PEN, May 2017  

Ladonna Pettus remembers the cover of Hemalog, a hemophilia magazine from 1990, promising “A Cure by the Year 2000?” It seemed at once like a vision and a done deal. Ladonna’s son with hemophilia was around two at the time. She recalls, “I had such hope. He is almost 30 now.”
Many parents who remember that magazine cover had those hopes. Their children are adults now, and although gene therapy trials are underway, it seems that the passion and dreams for a cure have been tempered. Alvin Luk, head of clinical research and operations at Spark Therapeutics, is working on hemophilia gene therapy. He offers, “We all underestimated the complexity of gene transfer.”
Maybe this is why, when I repeatedly asked 2,600-plus hemophilia “friends” on Facebook about their thoughts on gene therapy, only a handful of people replied. I’m sharing their comments here. Normally, the hemophilia community is vocal and active. Does this lack of response indicate that we are mostly unaware when it comes to gene therapy? Are we not sure what it is?
 
Defining gene therapy: A cure?
Parents and patients sometimes use the terms “gene therapy” and “cure” interchangeably. But the definitions aren’t the same. When we think of a cure, we think of eradicating the disorder or disease. In other words, a person with hemophilia no longer has it. In fact, a permanent cure for hemophilia already does exist. Steven Riedle notes that his brother with hemophilia had a liver transplant in October 2016, and is indeed cured of hemophilia. But a liver transplant is not a feasible option. 1 Many patients and caregivers are waiting—hoping—for a safe, widely available therapy that will cure hemophilia permanently. Yet we may need to adjust our definition of cure. Community members who responded to my questions seem to realize that most current gene therapy trials promise to make hemophilia less severe by increasing circulating levels of factor in the blood. Very few patients or parents understand gene therapy as thoroughly as Ray Stanhope, former National Hemophilia Foundation president, and person with hemophilia. He defines gene therapy as “the use of a viral vector to modify cells in the body to produce an additional specific protein which is either missing or produced at a lower than normal level in a person with hemophilia.”2 What Ray describes is not necessarily a cure, but an improved therapy.
 
What level of success?
If current gene therapy trials promise to increase circulating factor in the bloodstream, what level would be considered successful—a “cure”? Remember that severe hemophilia means less than 1% circulating factor, moderate means greater than 1% to 5%, and mild means 6% to 50%. Anything over 50% is considered in the normal range. 3 For Ray, levels of circulating factor would have to be well over 40% and closer to 50% (normal) to be considered a cure.
But others think that even converting someone from severe to mild hemophilia could be considered a success. Nichole Foley writes, “I think taking a person from severe to mild hemophilia is enough of an advantage for some of these kids that have constant challenges, and hopefully it will alleviate inhibitor issues.”
Bryce Loehrke says, “If gene therapy could permanently bring me to the levels of even mild hemophilia, I would consider myself cured for the most part. Having severe hemophilia A, I’ve often said that those with mild hemophilia don’t even have hemophilia. I don’t mean to diminish the fact that they still have issues from it periodically, but often with much less severity or frequency, sometimes to the point of not knowing they have it until later in life.” Tina Ruis takes this even further. “My 24-year-old son with severe hemophilia B—his left leg is unbearable. His calf is massive, and he can barely move without a walker. Levels of 11% to 15% would be worthwhile; over 25% would make me cry with joy.”
Stephen Brewer would be happy if gene therapy worked, even if it wasn’t permanent: “I would accept having mild hemophilia even if only for a few years.”
Chris Templin and his daughter both have hemophilia B. Chris notes that aiming for “mild” hemophilia is fraught with inconsistencies. “I think it’s interesting how people think all those with mild hemophilia bleed less then severe hemophilia patients. I know some milds who bleed more than some severe patients.”
 
The price of success
If gene therapy is successful and becomes available, how much would it cost? Some families think that because gene therapy trials are being held at university hospitals and hemophilia treatment centers, its cost may be lower than that of current commercial therapies. But this is not correct, because the trials are underwritten by pharmaceutical companies and the manufacturing process would ultimately need to be upscaled by a commercial pharmaceutical company.
    The issue of cost for a new therapy is complex, and includes these questions:
    • What is an acceptable therapeutic factor level: moderate, mild, normal?
    • How long will the treatment last: three years? permanently?
    • Will other factor products need to be used during the treatment period?
 
Ray estimates the cost of a one-time treatment of gene therapy at “close to $1 million, given the low number of patients, the cost of research and development, and assuming that the therapy is successful for four years.” He adds, “For the manufacturers, as much as they can charge; for the insurers, the least amount they have to pay.” Nichole Foley doesn’t care: “Cost-wise, I am sure it will be astronomical, but if [gene therapy] enables kids to live a normal life, I’d think it would be worth it!” Bryce believes, “If there’s an effective lifetime cure, $250,000 will be a lowball figure. We need to convince insurance providers of the long-term savings of a permanent or semipermanent cure.”
 
What if gene therapy is good for only a few years?
The term “cure” isn’t applicable at all if gene therapy—even if it brings your factor levels to normal—lasts for only a few years. This is a real concern.
Ray explains: “Given that the current vectors are viral and the immune system develops a response to that vector so that once used, it cannot be used again, this is problematic if the period of time that the treatment persists is short. There may not be time to develop an alternate type of vector. However, given the speed at which medical advances are occurring and accelerating, having the treatment persist for more than ten years might be enough to get you to the next vector, whatever that might be.”3
Amber Brandt, mother of a child with hemophilia, worries, “Regular factor is so expensive, I don’t see gene therapy being cheap by any means. And I’m sure it would be a huge struggle to get insurance to cover it. But if it only lasts a few years, I don’t even think it would be worth [trying] it at all.”
 
Wait-and-see approach
Patients who don’t see any solutions to these concerns may adopt a wait-and-see approach. Some are inherently mistrustful of playing with genes, or of the whole commercial industry of factor manufacturing. Some feel that current therapies are good enough for now.
Brandi Worthington admits, “I don’t know anything about gene therapy.” Amber adds, “It’s fascinating, but I would never choose that option for my son. He can choose that if he wants when he is an adult.” “I won’t be a first adopter for gene therapy by any means,” declares Bryce, “primarily due to distrust of the entire pharmaceutical industry for various legitimate and historical reasons. We need to know the consequences as well as benefits [of gene therapy].” Ray concludes, “Depending on the factor levels achieved and the duration of the treatment and the usable number of vectors…I might wait and see.”
 
Stepping-stone to a cure
Ray understands well the nuances and importance of educating the hemophilia community about gene therapy. Parents and patients will one day need to make an informed decision about whether to participate in it. “We as a community first need to define the parameters of what we would consider a cure,” says Ray. “I have always had a strict interpretation of this word. A cure would be a single treatment that provides normal hemostasis over the lifetime of the person living with hemophilia. Anything less than this should be considered a stepping-stone toward a cure.”
Stephen still has hope and carries the definition of cure even further. “Looking forward, a cure would include increasing circulating factor levels, [and] eliminate hemophilia from future generations [of a family].4 This is the ideal I hope for.”
1. Factors VIII and IX are produced primarily in the liver, although the cells lining the blood vessels also produce and hold reserves of factor VIII for release into the bloodstream when needed. Replacing the liver indeed cures hemophilia, but this is not deemed a viable option for treatment because it is too risky. Only patients with hemophilia who face liver failure are considered for this operation.
2.  A vector is a modified virus used by molecular biologists to deliver genetic material into cells.
3.  Among the general population, normal factor levels are between 50% and 150%, with most people being close to 100%.  
4.  Changing the genetics of future generations is not gene therapy, but human germline engineering. This practice is currently banned. It’s highly unpredictable, dangerous, and considered unethical.
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