New Publication Answers Questions About the SIPPET Study

Inhibitors are the most troubling complication of hemophilia A treatment today. In this week’s blog, I share with you a new publication concerning the SIPPET study, which sheds light on factor VIII products and inhibitors.
New Publication Answers Questions About the SIPPET Study


An article written by noted hematologist Dr. Flora Peyvandi and colleagues was recently published in the medical journal Haemophilia. This article directly addresses and answers several questions that were raised about the 2016 publication of the Survey of Inhibitors in Plasma-Product Exposed Toddlers, or SIPPET study.1

With this new article, SIPPET: methodology, analysis and generalizability, the authors respond to the 17 most common questions associated with the design, methodology, and results of the SIPPET study, including1:
  • Is the inhibitor risk higher in SIPPET than in previous reports?
  • Could differences in treatments between countries have affected the results?
  • Could the results have been affected by the way the study was randomized?
  • Do the SIPPET results also apply to other recombinant factor VIII (rFVIII) products
    beyond the 1st and 2nd generation products used in the study?
  • Is there a difference in inhibitor risk between the different brands within the plasmaderived and recombinant groups?
Original SIPPET Study
The SIPPET study, conducted by Dr. Peyvandi and colleagues, was the first randomized trial to compare the incidence of inhibitors in plasma-derived factor VIII (pdFVIII/VWF) products and rFVIII products in previously untreated patients (PUPs).2

Results from this landmark study showed that there was an 87% higher rate of inhibitor development in patients who received rFVIII compared with patients who received pdFVIII containing von Willebrand factor (VWF).2

Based on the results of the SIPPET study, the National Hemophilia Foundation’s Medical and Scientific Advisory Council (MASAC) now recommends that pdFVIII/VWF be considered as one of several treatment options in PUPs.3
Visit www.inhibitorinfo.com to Learn More About Inhibitors
Inhibitors are the most serious and challenging hemophilia A treatment complications. All patients with hemophilia A are at risk for developing inhibitors, regardless of age and disease severity.
Inhibitorinfo.com is a comprehensive website that provides important information and resources about inhibitors and the risk of inhibitors. There is a discussion guide patients can download and use to talk with their hematologists about inhibitors. Visitors can also read about the results of the SIPPET study and watch leading hematologists talk about its implications.
When visitors sign up for updates at inhibitorinfo.com, they will receive access to the full SIPPET study, as well as updates about hemophilia, inhibitors, and the latest clinical data.
References: 1. Peyvandi F, Mannucci PM, Palla R, Rosendaal FR. SIPPET: methodology, analysis
and generalizability [published online ahead of print March 17, 2017]. Haemophilia. doi:
10.1111/hae.13203. 2. Peyvandi F, Mannucci PM, Garagiola I, et al. A randomized trial of factor VIII
and neutralizing antibodies in hemophilia A. N Engl J Med. 2016;374(21):2054-2064. 3. National
Hemophilia Foundation. MASAC Update on SIPPET. National Hemophilia Foundation website.
https://www.hemophilia.org/Newsroom/NHF-Community-News/MASAC-Update-on-SIPPET.
Published March 9, 2016. Accessed April 27, 2017.
This is a paid public announcement from Grifols 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 Grifols website. LA Kelley Communications always advises you to be a savvy consumer
when contacting any company; do not reveal identifying information against your will.
BN/A8/0517/0275

Plasma-Derived vs Recombinant

A year ago we renewed a match between two heavy-weight contenders in hemophilia: plasma-derived products versus recombinant. The question: which product is more likely to cause inhibitor formation? In the fight to avoid inhibitor formation, some groups and opinion leaders read the initial results of the SIPPET project and declared plasma-derived the winner. But it’s a bit more complicated than that. Read Paul Clement’s excellent article on SIPPET; it will take many more rounds before we declare an outcome. The good news is that so much clinical scrutiny is underway.
The SIPPET
Bombshell
Paul Clement
A bombshell was dropped at the Plenary Scientific Session of
the 57th annual meeting of the American Society of Hematology (ASH) on December
6, 2015, in Orlando. Study coordinators of the SIPPET project (Study on
Inhibitors in Plasma-Product Exposed Toddlers)1 presented surprising
preliminary findings: recombinant factor VIII products are associated with an
87% increased risk of inhibitor development compared to plasma-derived factor
VIII products. 2
            In other
words, for every 10 people treated with recombinant factor VIII as opposed to
plasma-derived factor VIII, 1 patient can be expected to develop high-titer
inhibitors.
            As a parent
of a toddler who does not have inhibitors, you may feel stunned, angry, or
scared when you read these findings. Should you be? Before you rush to make a
product change, learn how the study was conducted, what its potential
shortfalls are, and why you should take a deep breath!
Shock and Awe
Understandably, many consumers are concerned. Some news
releases describing the study results only heightened the alarm. Hemophilia
Federation of America (HFA) issued a press release requesting that National
Hemophilia Foundation’s (NHF) Medical and Scientific Advisory Council (MASAC)
“consider the temporary suspension of recommendations… that state any
preference for recombinant factor products until the results of the full SIPPET
study can be reviewed.” 3
            Is this a
reasonable reaction, or is this jumping the gun? It helps to examine how the
study was conducted—and why.
Fighting Invaders
Why was the study looking to see if plasma-derived products
are less immunogenic than recombinant products—that is, less likely to lead to
developing inhibitors?
            In the
blood, factor VIII is normally tightly bound to another protein called von
Willebrand factor (VWF). VWF has several functions, including protecting factor
VIII from being digested and cleared from the bloodstream. Some researchers
suggest that in doing this, VWF masks some of the sites on the factor VIII
protein where antibodies attach, potentially making factor VIII with VWF less
immunogenic. Note:
            •
Intermediate/high-purity plasma-derived factor VIII products are the only ones
that contain VWF.
            •
Recombinant and ultra-high-purity (monoclonal purified) plasma-derived factor
VIII products contain no VWF.
Without the protection of its VWF “bodyguard,” the immune
system may recognize these factor VIII products as intruders and develop
inhibitors to neutralize them.
The problem is, no one really knows for sure what causes
inhibitors, and no one knows whether factor VIII with VWF is less immunogenic.
SIPPET Strategy
SIPPET set out to answer this question: Is plasma-derived
factor VIII with VWF less immunogenic compared to recombinant factor VIII
without VWF?
            SIPPET
researchers designed a study called a prospective
randomized controlled trial
(RCT). Prospective means looking forward,
before the patient has developed an inhibitor (in contrast to retrospective studies, in which
researchers look backward, after someone has developed an inhibitor).
Controlled means that there are two groups: (1) an experimental group that will
use factor VIII containing VWF, and (2) a control group that will use factor VIII
without VWF. This second group is used as a standard of comparison against the
experimental group. Randomized means that no one involved in the study
influenced which group a patient was assigned to. Randomization is often done
by a computer.
            RCT studies
are often considered the gold standard, thought to produce more reliable data
than other types of studies. Although an RCT can show relationships between
variables being studied, it cannot prove causality. So the RCT used for SIPPET
can’t prove that the presence or absence of VWF in factor VIII caused the observed results.
            SIPPET was
conducted between 2010 and 2015, and data was collected on 251 patients from 42
participating sites in 14 countries from Africa, the Americas, Asia, and
Europe. The patients were younger than six years old, had severe hemophilia A,
were previously untreated with factor, and had minimal exposure (less than five
times) to blood components. Of the 251 patients, 125 were treated with one of
the plasma-derived factor VIII products containing VWF. The remaining 126
patients were treated with a VWF-free recombinant factor VIII product.4 The
patients were followed to see if they developed an inhibitor, for 50 exposure
days (days they received factor infusions) or three years, whichever came
first.
            It’s
important to note that only one of
the plasma-derived products used in this study is available in the US, and that
the study was funded by manufacturers of plasma-derived products. Is this a
conflict of interest? Does it influence the findings?
SIPPET Shortcomings?
The preliminary findings were startling: of the 251
patients, 76 developed an inhibitor, and 50 of those were high-titer
inhibitors. And 90% of these inhibitors developed in the first 20 days of
treatment. Most important: recombinant factor VIII products were associated
with an 87% increased risk of developing an inhibitor compared to
plasma-derived factor VIII products containing VWF.
            Remember, these are not final results and have not yet
been reviewed by researchers outside of the study
. Before you decide
whether to switch your toddler to a plasma-derived factor VIII containing VWF,
know that many other variables affect inhibitor formation. In any experiment,
variables not directly being tested, but which could have an effect on the
outcome, are called confounding variables.
            For
example, the single greatest risk factor for developing inhibitors is the type
of genetic mutation that caused your child’s hemophilia. If the mutation in the
factor VIII gene resulted in no factor VIII being produced in his body, then he
is already at significantly higher risk of developing an inhibitor. This is one
of many confounding variables in the SIPPET study.
            One way to
reduce the effects of confounding variables on the data is to use a large study
sample. If the sample size is large enough and patients are randomly assigned
to two groups, then each group should have about the same number of patients
with the same confounding variable, so its effect will be canceled. The problem
is that the more confounding variables you have, the larger your study sample
size must be—perhaps several thousand patients. And many variables affect
inhibitor development.
            Another way
to account for the effects of confounding variables is to identify and measure
them, and then to separately compare and analyze the data from patients who
share the same confounding variable. This process is called stratification (meaning to separate into
layers) and was used by SIPPET along with other statistical analysis methods.
But the study identified and measured only six confounding variables: (1) age
at first treatment, (2) intensity of treatment, (3) type of factor VIII gene
mutation, (4) family history, (5) ethnicity, and (6) country site. What about
the effects of the other confounding variables that were not measured? If the
study sample size was too small to reduce the effects of other, unmeasured,
confounding variables, then the study’s conclusions are questionable and might
be explained in other ways.
Don’t Jump Ship Yet
At the time of this writing, SIPPET has not been published
in a medical journal. That means researchers—outside of those conducting the
study—don’t know much more about the study than you do after reading this
article. Only a short synopsis of the SIPPET study was presented at the ASH
annual meeting—just enough to cause a stir and raise many questions. You can be
sure that as soon as the journal article is released, it will be examined by
bleeding disorder experts worldwide. Questions will undoubtedly be asked about
the handling of confounding variables and whether the study sample size was
large enough.
            And experts
will have another question, too: Why didn’t the study include any of the new
prolonged half-life products, several of which appear to have a lower
immunogenicity than other recombinant factor VIII products?
            Should you
switch your toddler from a recombinant to a plasma-derived factor VIII product
containing VWF based on the preliminary SIPPET results, in the hope that it
will reduce the risk of developing an inhibitor? This is a question for you and
your hematologist, but if you were a betting person, the answer would be no. To
bleeding disorder experts, the results of SIPPET are not a bombshell, but
merely a piece of the puzzle that is inhibitors.5 The conclusions of this study
contradict those of several other studies. It may take years, and several
additional studies, to sort everything out. MASAC is on top of this, and as the
data becomes available, you can be assured that NHF will share its expert
opinion. So keep calm and carry on!
1.
https://ash.confex.com/ash/2015/webprogram/Paper82866.html (accessed Feb. 7,
2016).
2. Inhibitors are
a major complication of hemophilia in which a person’s immune system mistakenly
recognizes infused factor as a foreign (and potentially dangerous) protein, and
develops antibodies (inhibitors) to inactivate the factor, making factor
infusions ineffective.
3.
http://www.hemophiliafed.org/news-stories/2015/12/update-2-sippet-study-2/
(accessed Feb. 7, 2016).
4. The VWF-rich
plasma-derived factor VIII concentrates used by SIPPET: Alphanate (Grifols),
Fandhi (Grifols), Emoclot (Kedrion), or Factane (LFB). The VWF-free recombinant
factor VIII products used: Recombinate (Baxalta), Advate (Baxalta), Kogenate SF
(Bayer), or Refacto AF (Pfizer).
5. Visit the
Believe Limited website for an excellent interview by Patrick James Lynch of
bleeding disorder expert Dr. Steven Pipe about the SIPPET findings:
http://believeltd.com/inhibitors-sippet-and-the-double-edged-internet/
(accessed Feb. 7, 2016).

Blood: Time to Donate!

 

National Hemophilia Foundation recommends recombinant factor as the standard of choice for treatment of hemophilia, but did you know that many factor products used to treat
hemophilia are developed from human blood, specifically human plasma? In fact, one person with hemophilia can require up to 1,200 plasma donations for a one year’s supply of factor
products. Plasma products are especially important for those undergoing immune tolerance therapy to treat inhibitors, for those with von Willebrand disease and for those in developing countries.
 
And plasma can come from you! Think of making a blood donation, during this time of Thanksgiving and holidays.
 
First, learn a bit more about plasma, Plasma is the straw-colored liquid that makes up
approximately 55 percent of total blood volume. A single liter of plasma yields
coagulation factors essential for blood clotting, immunoglobulins used to
combat viruses and bacterial infections, and albumin, a major plasma protein
that regulates blood volume and other essential functions.
 
In addition to treating hemophilia, plasma-derived therapies
are used in everyday medicines, emergency and critical care situations, as well
as preventive medicine. Albumin, for example, is used to treat burns, shock,
trauma, liver conditions and cardiopulmonary illnesses; immunoglobulins are
indicated for Rh incompatibility, pediatric HIV, hepatitis, and animal bites.
 
Plasma is an expensive raw material and represents between 40 to 60 percent of the cost
of plasma-derived product production. This is due primarily to its biologic
nature: plasma protein therapies are not interchangeable, have no generic
variations or substitutions, and are defined as sole-source biologic products
by global regulators.
 
Since plasma is biological in nature, complex regulation and
oversight measures are in place—including collection, processing, and storage
and handling requirements—to ensure plasma donor health, as well as product
purity and efficacy for patients.
 
The majority of the world’s plasma comes from plasma donors
in the U.S. Collectively, the Food and Drug Administration (FDA) and its Center
for Biologics and Research (CEBR) are responsible for regulatory oversight of
the U.S. blood supply. Blood collection centers are either registered or
licensed by the FDA, and are held to quality standards comparable to those of pharmaceutical
manufacturers. Blood establishments located outside of the U.S. that import or
offer for import blood products are also required to register with the FDA.  
 
CEBR regulates the collection of blood and blood components
used for transfusions, as well as for the manufacture of pharmaceuticals
derived from blood and blood components. CEBR develops and enforces quality
standards, inspects blood establishments and monitors reports of errors,
accidents and adverse clinical events.
 
Manufacturing processes begin with fractionation,
followed by purification and virus inactivation. Fractionation is a time
consuming and complex process that extracts, or “fractions off,” specific
plasma proteins that have a proven health benefit. Fractionation requires
multiple processing steps, which involve manipulating solution pH, temperature,
ionic strength and alcohol concentration.
 
Once fractionated, plasma proteins are further subjected to
virus inactivation, a complex purification processes that includes prion
removal, nanofiltration, solvent/detergent
treatments and incubation, to ensure sterility and purity of the final product.
The complete manufacturing process, from plasma collection at a donor
center to the FDA’s lot release, takes seven to 12 months.

 

So donate now! Next year at this time, your donation could be used to save a life!
 
Sponsored by ASD Healthcare.
 
Great Book I Just Read
The Climb to Hell  [Kindle]
Jack Olsen
 
Olsen sure can write a page-turner. In 1957, one of the most audacious and stunning rescues to ever take place occurred on the north face of the Eiger, one of the most notoriously difficult challenges to scale, located in the heart of the Swiss Alps. The Eiger is feared for its avalanches, fast-changing weather, and sheer facade. When two poorly-prepared Italians set off to make history by being the first Italians to scale it, they become stuck for eight days, in zero-degree weather, unable to get off the mountain. This launches an international rescue effort, that leads to surprising outcomes, including national rivalry, clashing personalities, extreme risk taking and uncertain success. Fantastic story, well told and must-reading by all mountaineers. Four/five stars.

Under the Tuscan Sun: A Company Branches Out

Beautiful hills of Tuscany

If you’re my Facebook fan, you might know
I spent last week in Italy. I know, poor me. It was quite a change from two
weeks in India. All I need is Indonesia and I will have done my Eat, Pray, Love
hemophilia pilgrimage. Except I managed to eat in India, pray in Italy…. The
rest has yet to be seen!

I spent a few days in Florence before
heading slightly north for the real purpose of my trip. Florence is a city I studied
intensely as a teen. While other girls were going to dances, I studied the
Renaissance and became quite an “expert” at a young age. I copied paintings of
the masters, as I loved art, and when I first arrived at age 17, knew more
about where to go than our high school guide. So returning for my fourth time,
I resolved to wander the streets and churches, revisit the masters, and stand
in awe of the treasures of Italy. Nothing man-made captures my stunned, silent
respect and worship like the statue of David.
On day four I headed to Lucca, to visit a
pharmaceutical company called Kedrion. Kedrion came to our attention in the US a few years ago when it was contracted by Grifols to handle distribution of Koate-DVI, a
plasma-derived factor VIII product. Originally produced by Bayer, it was
divested, along with all the Bayer plasma division, to Talecris. Eventually
Talecris was bought by Grifols. But the US government, leery that Grifols now
had two plasma derived FVIII products, required Grifols to have a different
company handle distribution of Koate-DVI. Enter Kedrion.
Kedrion may be new to the US, but not to
Europe. Kedrion is a leading global pharmaceutical company specializing in the
development, production and distribution of a wide range of protein products
derived from human plasma. The company’s products are used to treat hemophilia,
immune deficiencies, infectious diseases and other serious medical conditions in
over 60 countries. The company owns four production facilities: two in Italy,
one in Hungary and one in the United States (currently leased to Grifols).
I was thrilled to be offered a tour of
the production plant. The plant is nestled among the Tuscany hills in Lucca, an ancient
city famed for its fortress-like walls that protect the denizens, once Romans
in 180 BC. The scenery—snow capped mountains rolling away to the sea; petite,
puffy clouds touching down on factories and churches— is breathtaking from the
patio of the Renaissance (how appropriate) hotel, perched on a mountain and once
owned by the Marcucci family, which also owns Kedrion.
I had dinner the night before the tour
with Paolo Marcucci, CEO of Kedrion, and wife Paola Pardini, whom I have met
before and who sponsor 17 children through Save One Life. With us was also
Danilo Medica, Italy country manager for Kedrion, who I had also met before at
a WFH event. Social events are always lovely with Italians, who know the fine
art of socializing, eating and drinking, and offering sincere and mutual respect
and hospitality.
Laurie at Kedrion plant, with
Charles Waller

So my purpose in visiting was to see the
plant, and learn more about this newcomer to the US market. Also, Kedrion has
been for a few years now our largest single donor of factor products to
Project SHARE, my factor donation program. We are now collaborating on ways to
secure even more factor to donate to the regions of the world where the 75%
live—those people with hemophilia with little or no access to treatment. Like…
some of the places I had just seen in India.

First, a snapshot: Kedrion was founded by
the Marcucci family; current CEO Paolo is son of the founder. It offers technology transfer of plasma collection to Macedonia,
Turkey, and Iran, as well as plasma-derived product sales to about 60 countries. It has 15 plasma
collection centers (nine of which are in the US). About 95% of its products are
plasma derived. Kedrion is one of the few factor manufacturers that is
considered part of a government healthcare system. About 75% of the company
is owned by the Marcucci family; 25% is owned by government.
Kedrion experienced enormous growth in the
past few years. Its business used to be only in Italy until just 2007; now it’s
been global for five years. A dominant 60% of its business is international,
part of this switch attributed to production acquisition sites in the US. It
has a FV product in the pipeline, even though there are only 5-6 patients with
FV deficiency in Italy. Clearly, Kedrion continues to have its eyes set on the
world.
And hemophilia in Italy? There are 3,481
hemophilia A patients; 1,688 are severe, 1,320 mild, and 473 moderate. In 2013,
FVIII consumption was about 555 million IU, with plasma-derived product use
actually increasing, driven by IT therapy for inhibitor patients.  Still, recombinant products dominate the
hemophilia market, at 66% of sales.
PLANT
TOUR
On a frosty Wednesday morning, I removed my jewelry, washed my hands thoroughly, suited up, and entered the plant with my
hosts, to tour how plasma products are made. The plant fractionates 1 million
liters (about 264,172 gallons) every year, using 24,000 liter tanks. First I
watched a film on the plant: how plasma arrives, is checked, monitored and
inventoried. How plasma is separated by centrifuge creating cryo paste for
fractionation. There are 480 employees in Lucca, and the plant operates 7 days
a week, 24 hours a day. It will be closed over Christmas for maintenance and
cleaning. The instruments and suites where products are made are cleaned daily.

On this tour I was able to watch albumin
being made. Albumin is the part of plasma used to bulk-up factor concentrates,
to allow them to be injectible. Alessandro, plant manager and our guide, explained
about different classes assigned to manufacturing suites (A-D), based on sterility
and cleanliness. As each product goes through each manufacturing phase, the
requirements for cleanliness gets more and more complex.

It’s not
just that things must be sterile. In the suite, people come and go; there is
air, exhalations, and ventilation. The air itself, pressurized like in an
airplane, to push air out if there is a breach, must be monitored constantly. You
want a low level of environmental pollutants such as dust,
airborne microbes, aerosol particles and
chemical vapors. Levels of contamination are specified by the number of
particles per cubic meter at a specified particle size. Instruments protruding
out of the wall measure constantly the ambient air, and would signal an alarm
if the air contained undesirable things in it at a level considered potentially
harmful.
We watched as lab employees handled the
sterile vials into which the albumin would be placed, all by machine to reduce
human contact. The rubber stoppers were placed, and the machines sealed it with
the foil. I learned something new: I always
thought the rubber stopper might be at risk to cause a breach of integrity of the vial
if the vial got too hot or cold. But Alessandro assured me these stoppers are
powerful and not likely to contract or expand with different temperature. It
really is about temperature control to keep the protein from degredating and
becoming less effective, less powerful.
Speaking of power, the plant must have
power at all times. What of there was a black out, someone asked? Kedrion is
self-sufficient in power, Alessandro explained. They produce energy themselves
using methane gas production.

Last, we learned about the “KQP”: Kedrion
Quality Program, an eight step system, using among other things, regular
qualified donors, NAT testing, pathogen inactivation, and TSE agents, to assure
that the products are safe.
The Italian Health System is complex,
making me realize we aren’t the only ones with healthcare budgetary woes. With 19
regions that are traditionally independent, 645 public
hospitals, 50 HTCs, and an ongoing economic crisis, the federal government is trying
to consolidate hospitals, and is asking for additional cost reductions from
industry. And yet Kedrion must continue to fractionate Italian blood and return
plasma-derived products back to the various regions.
One concern is that Italy’s not
self-sufficient in any product. Consumption is growing faster than production, but
consumption includes imported products at much higher per unit prices. In the
face of an economic crisis, slashed healthcare budgets, the question is: can
Italy use the products it has already to alleviate demand?
So that’s the point of my visit: in April
2013, Italian laws have changed regarding plasma. Previously Italian plasma had
to be used by Italians, but now the law allows Italian regions to recover costs
by selling the plasma products to other countries. Or maybe, donating? To India,
to Africa? We will see.
The name Kedrion comes from the Greek
language for lemon tree (or juniper or citrus, depending on your source). Its
symbol represents the deep roots Kedrion has in Italy, where the company was
built on Italian plasma and by a family dyanasty, and its branches go out into
the air, the world. I’m hoping they continue to branch towards developing
countries, to patients waiting to know this unique company and benefit from its
products.
To learn more about Kedrion: www.kedrionusa.com
Great Book I Just Read
Brunelleschi’s Dome by Ross King [Kindle]

The perfect book for reading while in
Florence. My hotel was about 200 feet from Santa Maria del Fiore, and when I
stepped into the cobblestone streets each morning, the massive façade, capped by the
astounding dome, greeted me. This book goes into great detail about what it
took to create the 37,000 ton dome, one of the largest cupolas in the world,
completed in 1436. It took 16 years to complete (over 100 for the Cathedral itself!),
and the architectural construction was filled with competition, craftiness and creativity. Brunelleschi
invented all kinds of new ways to transport marble, to hoist the marble. He was
a genius of architecture, and this Dome today still awes and impresses. This
story is compelling, and shows the potential of man to create and persist. Brunelleschi
was foiled many times, faced many obstacles, but finished it, leaving behind
one of the most prominent and important symbols of the Renaissance. A must read
for anyone going to Florence. But a fabulous book on any account. I climbed the
436 stairs to the top and was rewarded with a breathtaking view of Florence, one
of my favorite cities. It boggles the mind how this could have been created, at
such a time, with such vision. You’ll never look at a church steeple or
basilica the same again once you read this. Five/five stars!

Shopping Spree: CSL Limited to Buy Talecris

The hemophilia world is buzzing with the latest acquisition announcement: CSL Limited will buy Talecris Biotherapeutics Holdings Corp., one of the world’s leading manufacturers of plasma-derived protein therapies. One of these therapies is Koate-DVI, a plasma-derived factor VIII clotting concentrate. The move will make CSL a stronger competitor in the $15 billion global plasma products market. Selling price? US $3.1 billion.

How will this affect the US market, with so many changes underfoot?

One concern is what will happen to Koate DVI. CSL Behring already has two plasma derived factor VIII concentrates, Monoclate P and Humate P. Will it need three? We may be jumping the gun in speculating. Talecris is reaching out to its customers to assure them that the acquisition will not affect production for the foreseeable future. Below is a letter from Talecris, which I am reprinting with permission. We’ll be watching developments closely, and will let you know more in the near future. And let me add: we’ve been predicting consolidations, both in homecare and in pharma, for the past four years, and so they continue. We will monitor industry and as always, try to discern how consolidations and acquisitions, and product changes, will affect you, the consumer.

August 13, 2008

Dear Hemophilia friends, partners, and patients:

You may have heard Talecris Biotherapeutics and CSL have entered into a definitive agreement for CSL to purchase Talecris, pending the necessary regulatory approvals.

Please note that our commitment to provide high quality and effective products to our customers remains our paramount concern, and that has not changed — nor will a transaction affect any of our existing contracts to supply Koate-DVI Antihemophilic Factor (Human).

While the transaction moves through regulatory review, we will continue to serve our customers and the patients who rely on us by providing a reliable supply of safe and effective protein therapies. Additionally, we will continue to invest in improving our products, increasing the availability of our therapies, and developing innovations to enhance the lives of our patients. In short, you can rely on us now and in the future, however that future unfolds.

Talecris Biotherapeutics recognizes that the availability of Koate-DVI, is a paramount issue for the patients around the world. It is an issue of extreme importance to us, and one in which we have invested heavily to resolve for the patients we serve. In the past several years, we’ve invested over $150 million in the vertical integration of our plasma supply chain to enable long-term reliable supply, and tremendous progress has been made in taking the necessary steps to ultimately increase the supply of Koate-DVI.

* Talecris has invested significantly in our Clayton manufacturing facility, which operates nearly 24 hours a day, 365 days a year. In fact, we are completed an extended planned maintenance in order to significantly upgrade portions of our facility where Koate-DVI is produced. These upgrades will allow us to support increased worldwide demand and meet current commitments to supply Koate-DVI to our patients.

* Talecris Plasma Resources, Inc. (TPR), will further ensure a reliable, consistent supply of plasma for the long-term and we continue to invest significantly in improving the output of these centers and opening new centers.

* CSL, like Talecris, is a key global player in the plasma biotherapeutics industry dedicated to treating rare and serious diseases, and is passionate about improving the quality of life for patients throughout the world. We believe a combined entity would accelerate our ability to develop and deliver therapies that enhance the lives of patients who depend on us.

Thank you for your continued support.

Sincerely,

John Cutter
General Manager Intercontinental
Talecris Biotherapeutics, Inc.

Book I Just Read: How Elizabeth Barrett Browning Saved My Life by Mameve Mamwed
I don’t usually read fiction, especially not romantic fiction, but this book was a gift, and personalized by the author at that, so I could not avoid reading it. And I am glad I did: a little charmer of a book, easy to read and very well done. The real story’s about love, wrapped up in a plot about how an antique chamber pot turns the life of a struggling, young, intelligent antiques dealer with poor self-esteem upside down. Abby thinks her life is about to get better when the pot is appraised at $75,000, as it was once owned by poet Elizabeth Barrett Browning. But it’s the beginning of a lot of trouble, and a lot of introspection as to the nature of relationships when relatives and friends come out of the woodwork to get a piece of Abby’s fortune. I loved all the literary references and as it takes place in Cambridge, Massachusetts, hearing about places well known to us Yanks. Three stars.

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