February 2020

Origins: Part 2 Diagnosis

Six months went by fast and soon it was time for a baby. I never went into labor, so we had to jump start it with Pitocin, because I was two weeks overdue. I knew I was in for a long labor, so I grabbed my favorite book, Peter the Great, which I had already read. This is the book my mother had given me nine months ago, whose author’s son has hemophilia. Oh boy, would that make an impression soon. At the hospital, the nurses teased me as they saw me lying in bed in labor, reading this historical book with a yellow highlighter. “Studying for a test tomorrow?” one of them joked.

My baby was born by C-section and the next day, the doctor came into my room with a puzzled look on his face. He had circumcised our son, and “It bled for about 30 minutes,” he said, literally scratching his head. “In 30 years, I’ve never seen that.” In the back of my mind, I heard myself say, That author’s son has hemophilia…

He stitched our newborn up and when I saw him, he seemed fine. He was big–nine and a half pounds! We took him home two days later. One week later, around midnight, I went to change his diaper, and was shocked to see it saturated with blood. The entire diaper was red. I called the doctor, and he said to bring him to the ER. Our first ER trip at 1 am, with me still recovering from a C-Section. At that time Children’s Hospital in Boston was rather old and in need of repair. My husband went with our newborn into an exam room; they had me sit outside. I was crying to myself with no one around. Hearing my newborn scream for the next hour, two hours, was torture. My husband was excellent; he stayed with our son, talking to him, calming the situation down.

He looked perfect…

The ER doctor seemed more worried about me. It was 3 am, I was in the ugly waiting room alone, still not feeling great from the birth or lack of sleep or worry I could not stop crying. The baby’s screaming drove a knife through me. By 6 am, the baby was asleep, having survived the stitching, and we headed home, utterly drained. We had not slept in 24 hours.

It would be a month before we got the news. Meanwhile everything healed and life went on. Until the phone rang on a Friday afternoon in October. The voice of Jocelyn, a woman who would become our nurse and lifelong friend, was on the other end: “Laurie, this is Children’s Hospital calling. We have the results in from the blood tests. Your son has hemophilia A.”

Just like the author’s son. The author of the book I was reading the night I gave birth. The book my mother gave me nine months ago…

I felt a rushing noise in my ears that made it hard to hear what she was telling me. “Now, the clinic is closing for the weekend. If anything happens, if he bleeds, bring him in to the ER. We will need to give him an injection of medicine to clot his blood…”

While she was talking, I looked at my fluffy-headed, blond-haired one month old, innocently asleep in his bassinet, wearing a onesie. He looked perfect. What was this woman talking about? This was like a jail sentence!

I knew how to fix this. I hung up on her. And felt instantly back in control.

Next week: First clinic visit and weird circumstances continue!

Origins

This is our 30th anniversary of LA Kelley Communications—amazing! We’ve been publishing original books and newsletters on bleeding disorders for 30 years now, and started programs to help families struggling in developing countries. We originally started just to help new US moms and dads, but grew to have global impact. We continue to assist families with bleeding disorders worldwide with educational and financial resources.

Sometimes I am asked how I started, and why I started. I often give the short version: In 1987 I gave birth to a son with hemophilia, and was so terrified, and had such scary experiences, that I decided to write a book sharing parents’ combined wisdom. It launched a new career.

The longer story is way more interesting —and mysterious! Kind of like Twilight Zone material. Interested? Stick with us—we are going to go deep into how this all came about!

Laurie Kelley graduates with friends Ellen and Gretchen
Tufts University 1986

So I had just graduated in May 1986 from the Tufts University’s Fletcher School of Law and Diplomacy at age 28, with a Master’s Degree in International Business and Economics. I had a small apartment near Tufts, and walked to school daily. I actually put myself through school, while paying all my own living expenses. I was completely broke and in debt, but about to get married and land what I hoped was my dream job. Typically, I had everything planned to the nth degree. I even paid for my own wedding. How I did this on $5,000 a year, while working for my professor, seems inconceivable now. College was and is not cheap. Neither is getting married. My gown came literally off the floor at Filene’s Basement, and we found a great reception hall that was subsidized by the military. A friend of ours was an officer. It all helped. Married, July 12, 1986.

Our plan was to land good professional jobs, pay off our debt, wait five years before having children, and buy a trophy home. It was the 1980s after all!  We both landed good jobs: I ended up at DRI, a private forecasting company in Lexington, Massachusetts. Kevin ended up at Biogen, which at that time completely fit into one building in Kendall Square, Cambridge.

With grandmother and mother, July 1986

I recall one night going out, but Kevin told me he had to first check on his Chinese hamster ovaries. A process scientist, he was working on a drug for hemophilia. We stopped by Biogen and I got to peek at hamster ovaries. Weird circumstance #1.

At Christmas 1986, we visited my mother in Springfield, Massachusetts, my home town. I don’t recall whet gifts we gave one another, but I do recall distinctly that before I left to return to Boston, she said she had one more gift. She handed me the paperback of Peter the Great, by Robert K. Massie. She off-handedly added that the author’s son has hemophilia, and this is why he wrote about Russian royalty. Weird circumstance #2!

Well, I love history and am a voracious reader. I happily accepted it, read it right away and it immediately became my favorite biography. It pretty much still is.

Little did we know that I was pregnant when she handed me the book. Weird circumstance #3.

One of my favorite books ever!

In February we all went skiing one day on a Biogen-sponsored ski trip. I recall my skinny skipants not fitting too well. Must be happily married, haha!  I recall not having any kind of balance. I fell a lot, even on the “bunny” slope, which made our gang laugh at me. Face covered in frosty snow. On the return trip, we stood in the aisle of the crowded bus as it rocketed down the highway, chatting with friends, when suddenly I, who never in my life got motion sick, felt like vomiting. I raced to the front of the bus, sat in someone’s vacant seat, and composed myself. The nausea passed. Then I noticed someone had left half of a roast beef sub stuck in the back pocket of the seat in front of them. No one was around, and I suddenly grabbed the sub and devoured it. What was I doing?

I found my husband and said to him that something was really wrong with me. My eating was out of control. Maybe you’re pregnant? he said half-jokingly. Not a chance. That was not in the plan. We had debts to pay off and a trophy home to buy.

But a trip to the doctor the following day confirmed it. You are really pregnant, the doctor said, Like three months. He looked at me funny. Yes, my husband and I both had master’s degrees, but work was keeping me very busy. Too busy to notice what was happening to my own body.

Once the shock wore off, we were over the moon excited. The baby was not planned, and I’m still not sure quite how it happened, but we were going to be parents!

Pregnant? Surprise!

Next week: The diagnosis.

Thirty Years of Education and Innovation!

It started with the birth of a baby with hemophilia, then a book… and a company was born. Thirty years ago I founded LA Kelley Communications to meet the need for information about hemophilia from a parent’s point of view. In 1990, there was no book on hemophilia to help parents master raising a child, no newsletter geared towards them, written by parents, no children’s books about hemophilia, and of course, no internet, social media… heck, we didn’t even have cell phones!

Some of you might recall our first logo!

We were all pretty isolated, and the national community was busy battling the drug companies and government about the HIV scandal. I decided to create the educational materials I needed, and share them with other families. And we’ve been doing that ever since!

Next week I’ll share the actually beginnings of our company and work, but for now, did you know we hav a long list of firsts in the bleeding disorder community? They are listed below…. and all of our sponsored books and newsletters are free to families… and they always have been for 30 years. Congratulations to us!

We provided the:

Or maybe our second logo?

• First patient-run hemophilia consultants (1990)

• First US hemophilia parenting book (1990)

• First VWD Book (2004)

• First parenting/consumer newsletter (1990)

• First children’s books (1992)

Our international
leadership program

• First and only book on inhibitors (2002)

• First quarterly e-newsletter (2000)

• First dedicated blog: HemaBlog (2006)

• First leadership training programs (1996)

• First direct-to-consumer marketing (1996)

• First private international factor donation program (1996)

Next week: How it all began!

Prepare for Big Changes

When we use the word “transitions” in hemophilia, we normally think about our child’s life cycle (or our own) and how it impacts healthcare: Children transitioning into adulthood at age 18 need to see an adult hematologist, not a pediatric hematologist. Adults finishing college or trade school need to transition into the workforce. Adults at age 26 need to transition off their parents’ health insurance. We may have joint issues as we age.

But we can also view transitions as something happening to hemophilia treatment, because that has a life cycle too. And right now, hemophilia treatment is undergoing massive, rapid change. New products, novel therapies, and gene therapy…can the US market of roughly 20,000 with hemophilia support all the products? Will insurance cover them all?

A Look Back: Our Infancy

If we accept that hemophilia treatment has a life cycle, let’s look back at its infancy and development. Early treatment for hemophilia involved whole blood transfusion and later, human plasma. Fresh frozen plasma (FFP) allowed treatment to be stored and then thawed when needed. Whole blood and FFP were both only marginally effective at controlling a bleed, due to the low level of factor VIII and large volumes that needed to be infused. Then, in the mid-1960s, came cryoprecipitate: rich in factor VIII, and created from thawed human plasma. Its higher factor VIII level in a smaller volume made administration easier, faster, and more effective.

A breakthrough came with commercial clotting factor concentrate in 1968, made from donated human blood or blood plasma. This new plasma-derived concentrate was freeze-dried and reconstituted with water when needed. Factor in a bottle! Now treatment could be done at home or away, freeing patients to travel and live more normal lives. Infusion time was tremendously shortened, meaning treatment could stop bleeding faster, reducing pain and helping to prevent joint disease. But these early factor concentrates were not treated to inactivate viruses. Tragically, in the late 1970s and early 1980s, contamination of the nation’s blood supply from donors infected with HIV, hepatitis C, and other viruses meant that clotting factor was also contaminated. Thousands of people who had hemophilia and used factor concentrates were infected and died.

In the mid-1980s, a new stage in the life cycle of hemophilia treatment emerged: the creation of factor that was virally inactivated. Viral inactivation processes, such as heat or solvent/detergent wash, could destroy the fragile HIV. Today, all clotting factor is considered safe.

The deaths of so many led to another groundbreaking stage in the life cycle of hemophilia treatment: recombinant clotting factor. Recombinant factor is produced in a lab, using human genes that are inserted into genetically altered mammalian cells. In 1992, the first recombinant factor VIII clotting factor product (Recombinate, manufactured by Baxter) was approved by the FDA. In 1997, the first recombinant factor IX product (BeneFix®, manufactured by Genetics Institute) entered the market. And now? There are now about 20 recombinant factor products on the market to treat hemophilia. We’ve come a long way.

The Family Expands: Crying for Attention

Why so many products? There are some things to know about the factor market. First, the US is the largest market. Not in population—that would be China. But in dollars. Estimates are $4.6 billion annually.1 This lucrative market attracts competitors. But factor products are protected by patents. So to avoid patent infringement, changes or improvements are made to products, making them slightly different. Some of these changes have involved production processes; and the quest to remove unnecessary human and animal proteins gave us “generations” of recombinant factor products.

Now we have three recognized generations of factor products: First-generation products use animal blood proteins in the cell culture medium, and add human albumin, a blood protein, to the final formulation to stabilize the factor. Second-generation products stabilize the factor with sucrose, not albumin. Third-generation products use no added animal or human proteins, either during processing or in the final formulation.2 Today, all factor products except for Recombinate and Kogenate® FS are third generation. A special shout-out to Octapharma’s Nuwiq®, a recombinant factor VIII product that uses a human cell line instead of an animal cell line in its production process.

Recombinant products, by reducing the potential for viral transmission, are an improvement over past products. And yet first-generation products remain in use, as do plasma-derived products. So far, there seems to be a purpose and a place for all products.

Growth Spurt!

But consumers want more. Researchers found ways to keep infused factor circulating in the body longer, by extending its half-life—meaning fewer infusions and less burdensome treatment. Eventually, extended half-life (EHL) factor was created. After a relatively calm 10 years in the marketplace with what is now called “standard half-life” or just “standard” factor, EHL factor came along, resulting in a big growth spurt in the life cycle of hemophilia treatment. Hailed as the next best thing, EHL factor was and still is heavily promoted. Biogen created the first two EHL products, which were soon followed by EHL products from Baxter (now Takeda), Novo Nordisk, Bayer, and CSL Behring.

  The creation of EHL products seemed like the exciting, wild teen years for our community. Children with hemophilia lived even more normal lives, without infusing so often. Freedom!

Family Feud

In the midst of this growth spurt and innovation, some major shifts were taking place in the hemophilia marketplace. Companies were separating, divorcing, getting married, taking on lovers, adopting other products. Baxter split off its biological division (which made its factor products) to become Baxalta. Genetics Institute was bought by Wyeth, which was then bought by Pfizer. In the early 2000s, Bayer had divested its plasma division, which became Talecris. Then Grifols bought Talecris (you can still see the primary color bar on the Koate®-DVI box, the same bar that appears on Kogenate FS). Biogen, soon after launching its groundbreaking EHL products, suddenly divested its hemophilia group, which became Bioverativ. Soon after the new sign was up at Bioverativ’s headquarters, it was bought by Sanofi Genzyme. Baxalta must have been a very attractive mate, because soon after it was spun off by Baxter, it was snatched up by Shire, an Irish pharmaceutical company. Just when everyone was getting used to Irish brogues, Shire was purchased by the Japanese company Takeda, a pharma titan.

 Perhaps no products have changed hands more than those of CSL Behring, starting in the 1980s, when it was Armour Pharmacuetical. And although CSL Behring has remained the parent company since 2007, it has recently abandoned some hemophilia products: Helixate® FS and Monoclate-P®. Its focus is now on EHL products only for hemophilia.

And this is the concern for the future life cycle of hemophilia treatment: Can the market sustain 20 recombinant products? Which products will be removed next from the marketplace? Will product change come from the consolidation of companies buying each other and reducing overlapping product lines? Will it come from flagging sales, if one product dominates the market? Or will product change come from a novel treatment—using no factor at all?

Newest Child

One product getting a lot of attention these days is the newest addition to the family—Hemlibra®, a nonfactor antibody product that mimics the action of factor VIII in the body. It’s used for prophylaxis in people with hemophilia A and inhibitors, and in those without inhibitors. The product’s clinical success has many patients cheering on Facebook, some advocates cautioning consumers to wait and see, and some doctors already prescribing it for newborns. Hemlibra is called a “market disruptor” for a reason. It’s created a whole new way to treat hemophilia: with weekly to monthly subcutaneous injections. And people with inhibitors are reporting no bleeds for weeks, even months in some cases. Will factor concentrate still be needed? Read Wendy Owens’s feature article in this issue to learn the answer!

The life cycle of hemophilia treatment has entered a new phase, perhaps similar to young adulthood, where there are many options, and our community has been educated and prepared. We’re ready for greater independence from this disorder, and ready to live life more on our own terms.

But like all young adults, we still need advice from our elders, from our blood brothers, from our physicians. And we need to do our own homework. We need to read about current products and new ones that will enter the marketplace. Do you feel informed enough to choose? Will your insurance cover all the new products? Will you switch to another product, if one day your insurance company no longer covers yours?

 Stay in touch with the life cycle of hemophilia treatment: name changes of the corporate players, which products belong to whom, and especially, the manufacturer of the product you use. Decisions at the top—by government, by corporations, and by insurance companies—may eventually impact your choice of treatment.

We have more freedom and more choices than ever before, but we need to exercise responsibility, by learning all we can. Because one thing is for certain: we are only in the young adult stage of hemophilia therapy. Prepare for more growth and more change.  It’s coming.

  1. Mark Terry, “A Look at Hemophilia Drug Prices and the Market,” biospace.com, July 3, 2018 (accessed June 2, 2019).
  2. Recombinate is a first-generation recombinant product. Kogenate FS is a second-generation product. Advate, Adynovate, Afstyla, Alprolix, BeneFix, Eloctate, Idelvion, Ixinity, Jivi, Kovaltry, Novoeight, Nuwiq, Rebinyn, Rixubis, Vonvendi, and Xyntha are third-generation products.
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