The Age of Gene Therapy: Why Plasma?

It’s happened: gene therapy is available, at least for hemophilia B patients in the US. The idea that hemophilia can be treated as a “cure,” or at least using one shot to cover your bleeding episodes for at least a few years, is tantalizing. And if not that, we still have recombinant products that have never touched human blood.

We just updated our factor chart here, which compares all the products available on the market for hemophilia A and B. You have lots of treatments to consider! But why are we still making plasma-derived products?

A few reasons. But first, understand where plasma-derived products come from.

Plasma-derived products come from human blood plasma. Plasma donors undergo strict screening for disease risk factors, and their plasma is tested for several viral diseases. Recombinant products are not derived from blood; they originate from genetically engineered mammalian cells containing the human gene for factor. Recombinants are produced in large bioreactors, with human and animal proteins used in the culture medium in first- and second-generation recombinant factor. Third-generation products contain no human or animal proteins in the culture medium or the final product. Fourth-generation products are made from human cell lines.

Although plasma-derived products potentially risk transmitting blood-borne viruses, all US factor products, whether plasma derived or recombinant, are considered safe by the FDA.

Why would anyone intentionally choose a plasma-derived product instead of recombinant? After all, recombinant factor is the product recommended by NHF’s MASAC. And now we have gene therapy for hemophilia B. Why inject anything other than the missing factor into your child?

For some people, it’s all about cost. Plasma-derived factor is less expensive than recombinant factor. And gene therapy is expected to cost about $3.5 million per shot. People who have high out-of-pocket expenses need safe products, but may choose less expensive ones. Sometimes, the decision depends on the type of bleeding disorder being treated. For example, intermediate purity factor VIII products contain factor VIII combined with VWF (the way it’s naturally found in the blood) and are useful in treating von Willebrand disease.

When choosing your factor therapy, always discuss options with your HTC! Use our factor product guide here, which now includes bispecific antibody products and gene therapy, and bring it with you, and ask what’s best for your loved one or you.

Texts That Protect

If something big were happening, you’d want to know about it right away, especially if it concerned the factor you or your loved one uses. The Patient Notification System (PNS) is a free service that will notify you about any withdrawals, recalls or warnings concerning your specific product, and even ancillaries. Are you signed up with it?

Launched in 1998 by the Plasma Protein Therapeutics Association (PPTA), a group that is supported by manufacturers of plasma-based products and recombinant products, this system has diligently sent out hard copy, telephone and email notices of any changes in your prescription drugs.

There was a time in the early 2000s when these were frequent, as there were shortages, plant shut-downs, recalls, products taken off line, and more. You can imagine that the specter of the mass HIV infections in the blood supply in the 1980s led to this unique and vital service.

There’s good news now: stringent manufacturing practices, better donor screening and genetically-engineered products means that notices of safety concerns are almost a thing of the past.

Are you signed up? You should be. It’s free, confidential, and now fast! Just recently, the PNS added notifications by text, probably the fastest route these days.  You will want to be up to date on any changes in the product you use.

Sign up for the PNS at or call 888-UPDATE-U.

Types of Factor Concentrate

Last week we shared new about Sevenfact, a commercial blood clotting recombinant product made from transgenic rabbits. But that made me think: maybe we should step back and review what types of factor products there are to begin with.

There are different kinds of factor concentrates, all with distinct brand names and made by different companies, but all blood-clotting factor concentrates are classified as one of two types:

Plasma derived • Recombinant

The major difference between the two types is the origin of the factor, called the source material.

• Plasma-derived factor originates from human blood plasma.

  • Recombinant factor originates from genetically engineered mammalian cells containing the human gene for factor (not from human blood).

You might think that recombinant products have an advantage because they don’t come from human blood, but some still contain extraneous (unwanted) proteins—human and even animal. To understand the differences among products, you first need to know how various factor products are manufactured.

Plasma-derived factor concentrates are categorized by their degree of purity. Recombinant factor concentrates are categorized by how they are produced. Different—although very similar—manufacturing processes can create products with slight molecular differences in the factor protein and with varying degrees of extraneous proteins in the final product. Here are classifications of factor products, based on varying degrees of purity or differing manufacturing processes:

Plasma derived

• intermediate purity • high purity • ultrapure (monoclonal)


• first generation • second generation • third generation • fourth generation

Several recombinant factor products also have a prolonged half-life, allowing you to infuse less frequently. The first of these new products was introduced in 2014.

Why are there so many kinds of manufacturing processes? Why not just use one method to produce factor? In some cases, it’s partly a legal matter: if manufacturer A creates an effective way to produce factor, then A usually patents the process. No one else can use it. Manufacturer B will need to find another way! So manufacturers have developed a variety of slightly differing processes to produce factor.

It’s also a matter of purity and safety. Different products use differing source material and require specific types of manufacturing methods to ensure safety. Due to varying production methods and the type of factor, the relative purity of the final products varies. Purity and safety are two terms you must understand to know which brand of factor to choose, because not all factor concentrates are created equal.

Do you know the difference between purity and safety? It’s easy to confuse them. We’ll review them next week!

Excerpted from Raising a Child with Hemophilia, Laureen A. Kelley 2016

Wilate: a New VWD Product

This is big news for von Willebrand Disease patients: there’s a new product on the market. Wilate® just got approved by the US FDA for “treatment of spontaneous and trauma-induced bleeding episodes in patients with all types of von Willebrand disease (VWD),” according to a press release. Wilate is a high-purity plasma-derived product, which uses a double viral inactivation process in manufacturing: solvent/detergent (S/D) process and a special terminal dry-heating (TDH) system. No albumin is added as a stabilizer. Wilate is exclusively derived from large pools of human plasma collected in U.S. FDA approved plasma donation centers. Wilate will be available in the market in early 2010.

Wilate is produced by Octapharma, a Swiss-based company. This is the first time Octapharma has entered the US bleeding disorders market. Wilate will be in direct competion with Humate-P, manufactured by CLS Behring.

One thing interesting I learned is that this is the first product developed and manufactured specifically for VWD.

Here’s a quote from Octapharma: “Octapharma’s worldwide commitment to coagulation disorders dates back to Octapharma Group’s formation 25 years ago,” said Octapharma USA President Flemming Nielsen.”We are thrilled that U.S. patients will now have access to Wilate following its significant success in Europe as a next generation therapy. Octapharma is committed to providing the U.S. market with life-enhancing therapies.”

VWD patients now have more choices for treatment options. For more information, please visit

Great Book I Just Read
Final Voyage: A Story of Arctic Disaster and One Fateful Whaling Season by Peter Nichols

Massachusetts (my home state) gave birth to the American Revolution and also the global whaling industry. This fascinating book recounts a terrible story of scores of whaling ships trapped in the Arctic region, as the captains tried to score as many whales as possible before the ice closed in for the winter. Nichols deftly parallels that story with the beginning of the whaling industry, which has direct ties to Puritans coming to the new world, religious intolerance in Massachusetts in the 1700s, and the Quakers, who almost single-handedly created this lucrative industry. Whale oil soon was lighting the homes of Massachusetts and then lubricating the machines of the Industrial Age, making some Quakers millionaires, even then. Nichols also details the decline of the industry: the discovery of crude oil in Titusville, Pennsylvania, which soon replaced whale oil; the decimation of so many whales left hunting lean. All these events culminate into a dreadful outcome for the ambitious captains of the whaling ships that last season of hunting, as they searched for the last whales in an early and fearsome storm. This book will enlighten you about many subjects, from religion and commerce, to whales and history. Three stars.

Plasma Showdown!

I was lucky enough to be a speaker at the North Carolina Hemophilia Foundation event last weekend, and on my favorite subject–hemophilia in the developing world. This was a jam-packed event with an all star list: Ray Stanhope of the NHF; Mike Rosenthal of the WFH; Carl Weixler of HFA, Richard Atwood, president of NCH. Richard writes a column for my newsletter called “Richard’s Review” and I think is the foremost authority on any book or movie ever released in history that might even mention the word hemophilia! It was great to see everyone at the event.

But the best presentation was the “showdown” between famed Dr. Harold Roberts and the ever-delightful Dr. Albert Farrugia of the PPTA, who speaks with a lovely Maltese accent. Both men are brilliant and excellent speakers. Dr. Roberts is decidedly pro-recombinant factor, and Dr. Farrugia strongly makes a case for plasma-derived, and with lots of wit and fun, they sparred about their topics, until Dr. Roberts said good-naturedly, “Why don’t you go back to Australia?” The audience roared with laughter; they were educated and entertained!

Seriously, this is a fascinating topic–plasma-derived vs. recombinant–and one we will explore in PEN in August. Be sure to sign up for a copy!

Thanks to Sue Cowell, executive director of NCH, for inviting me to such a great event.

Book I Just Read: Pete Duel: A Biography

This book reveals the darker side of celebrity, in the story of a 1970s TV star, best known for his role as Hannibal Heyes in the TV series Alias Smith and Jones. The show was a spin off of the 1969 Best Picture nominee Butch Cassidy and the Sundance Kid, starring Paul Newman (who is beloved to the hemophilia community for his Hole in the Wall Gang camps). Duel was a talented rising star, but battled epilepsy and alcoholism, but more than likely something undiagnosed, like manic depression. Like his name, he exhibited a personality described alternatively as sweet and loving, kind and generous, then venomous and raging. He hated the TV show that made him famous, and hated TV in general. He committed suicide at age 31 in December 1971 while in an alcoholic stupor. The book tries to detail his life, but comes across as flat, unsympathetic and groping for answers, which don’t materialize. The book seems more a tribute to Duel with heavy input by Duel’s sister, but it’s depressing overall. Duel simply did not accomplish that much in his young life, compared to others who died young, like James Dean or Jim Morrison. One star.

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