“Are you a madman or a guinea pig?” asked a man from France at the final symposium of the World Federation of Hemophilia Congress in Paris, France last Thursday. He addressed his question before the 500 or more attendees in the huge amphitheater at the Palais de Congres to our own George McCoy, from North Carolina, one of the fascinating speakers on the panel debating and comparing long-acting factor to gene therapy.
Laurie Kelley with George McCoy, from North Carolina
Great question, particularly as George had just revealed that he was the very first human ever to be injected with recombinant factor VIII, back in March 1987. I was riveted to George and his reply. The whole audience was. But more on that in a bit!
The session opened with Dr. Paul Giangrande, director of Oxford Haemophilia Centre in England and world-renowned hematologist, purposely supporting continued recombinant therapy, and listing the many pros of our current treatment. Paul reminded us of the Hippocratic oath Primum non nocere: First, do no harm, and cited the long and many years of improved quality of life and quantity of life on these therapies.
(Dr. Giangrande also prefaced his presentation with an outrageously humorous skit on how he gets roped into presenting so many talks at symposia, all seemingly taking contrary positions! He feels it is his duty to provide food for thought on the pros and cons of all treatment; here, he was asked directly by WFH to make a case for recombinant therapy)
Long acting factor, Dr. Giangrande said, which many manufacturers are working on, is based on recombinant technology, a stable and known technology, which is considered safe. It provides breadth of product for factor VIII, IX, and inhibitor patients. WFH president Mark Skinner even said earlier at the Congress that treatment should aim for a trough level of 15%—which recombinants can provide. Giangrande added that we know the manufacturers already so we know in essence from where the product comes and what we are getting.
Giangrande then cited some of the downside of what we know and can expect from current gene therapy, still in clinical trials: more hospitalvisits and blood tests. He asked if patients truly were giving informed consent. Most parents don’t understand what the studies involve. And he questioned the
ethics of using patients in developing countries in these clinical trials—there are medical risks, and the patients could be desperate to have product no
matter what.
Will gene therapy really lower costs? Currently Dr. Kathy High from Children’s Hospital of Philadelphia is investigating a factor IX gene therapy treatment. If successful, Giangrande reminded us, it will be commercialized, just as all the past research in hemophilia has been.
Next came Dr. Kathy High herself, who reminded the audience right away that the ultimate goal is to cure hemophilia. We aren’t used to thinking of cures for genetic diseases. Some have been radical, such as bone marrow transplants or liver transplants. But we have alternatives now. In a recent published gene therapy article, research in the UK showed that a single infusion led to more than 18 months expression of factor IX at
about 5% levels. This was repeated in two other patients. Unfortunately, eight weeks later one patient required steroids. While it looks like a virus vector may trigger an immune response, Dr. High felt that the risk of a short course of steroids outweighed the risk of bleeds. Other risks noted included the viral vector appearing in semen; and one mouse model showed an increase in carcinoma (but he was an old mouse with lysosomal storage disorder! The things you learn at these symposia).
How long will this gene therapy last in the body? We don’t know. In dogs, over ten years. And it only requires a simple infusion, with no organ transplant.
Richard Minja (Tanzania), Neil Herson (President, ASD Healthcare), and Simba (Zimbabwe)
Dr. High posed the question on everyone’s mind: when will gene therapy happen for hemophilia A patients? High believes it will start in 3-5 years. Some studies are already underway, such as one with AV canine factor VIII, with Dr. David Lillicrap of Canada. High gave a positive and detailed summary of currently gene therapy—very exciting presentation!
So back to George McCoy, who then spoke, eloquently, sincerely and humbly. He described his childhood, and how he was diagnosed at age two. One of four boys, his eldest brother Richard had hemophilia for years and no one knew. Sadly, he died. George’s speech was moving and thoughtful, especially when he cited WFH founder Frank Schnabel, who described patients with hemophilia as “tortured pieces of human geography
confined to a wheelchair.”
Dr. Gil White contacted him about being the first rFVIII patient ever in March 1987, and hence the question: is he a madman or a guinea pig? George simply replied that he would do it all again if he had to—he would volunteer for gene therapy if—or when—the time comes. And he stressed that we need volunteers for gene therapy now.
He closed with the beautiful thought: “What brings us here is the will to live, the
will to prosper, the will to learn. We all do need each other.” And while all
the speakers weighed in on whether they would elect gene therapy over
long-acting factor for their hypothetical grandchildren with hemophilia, were
they to have one, it was Dr. High who made a memorable statement: we need access to all therapies, both gene therapy and long-acting, for individual patients with
individual biological make-ups, for those in developing countries— access to all products and treatments for us all. George was right: we all do need each other, and this past week at WFH reminded us all that 300,000 have little or no access to hemophilia treatment. The burden—to me the joy— is on us to help them all.
CEO of Biogen, George Scangos, Laurie,
Sr. VP Medical Affairs, Biogen, Glenn Pierce
I happily drove an hour to Westwood, Massachusetts to attend the New England Hemophilia Association’s Springfest, a gathering of local hemophilia families and the companies and medical people who serve them. It was a glorious, sunny day and a wonderful event.
Val Bias, CEO of NHF, attended to present an overview of NHF’s programs and also how funding is raised and where it is spent. Here are some stats:
• There are 57 full time and part time staff at NHF over 10 states
• There are 8 regions for HTCs now, down from 12
• NHF has a PDF you can download called “50 Steps to Cultivating Donors”
• 50% of the NHF’s board of directors are not related to hemophilia
• 52% of its budget comes from pharma
Val stressed to the audience to get involved locally, and to consider joining the NEHA board. He made a compelling plea and is an excellent speaker. Many people told me later they thought Val is a gifted presenter and a wonderful leader for our community.
Next up was a great presentation on gene therapy and new products coming soon by Dr. Ellis Neufeld of the Boston Hemophilia Center. Dr. Neufeld did an amazing job of taking highly complex material and breaking it down for us. Some highlights:
• The St. Jude gene therapy trial that has been in the news: only 6 FIX patients in trial, using “gutted” virus (no capacity to reproduce).
• Of 6, only 1 really took to it but he got higher ALT (liver
function measurement).
• Problems with the study: not enough data, immune response a threat and you can’t be retreated
as you will have an immune response.
• Long acting factor: many companies working on this. Everyone has different half-lives; children have shorter
ones than adults. So how long is long? New FIX drugs could be 3-5 times longer acting, meaning you might treat once every 10-14 days?
• What will price be of the longer acting drugs? What is the worth for a theoretical improvement of
life? No one yet knows.
(Our next issue of PEN in May examines all these in depth: be sure to download it!)
Dr. Neufeld was very positive about current gene therapy efforts. He made us all laugh by saying that our community has been promising us gene therapy roughly in every ten year cycles, but this time, he truly feels there is a great chance we will find it.
Just before lunch, we had panel presentations from all the pharma and specialty pharmacy reps on their patient assistance programs, delivered all above the growing din from the Bar Mitzvah next door!
These were all great presentations, and we had an attentive audience. I saw so many of my friends in hemophilia, and truly enjoyed myself. I hope you can all attend a local hemophilia event and take part in your community! We had a rap session with the moms, and one among us had an 8 month old. We all remember the feelings of when our babies were diagnosed. We felt for her. Everyone rushed to welcome her, praised her for attending, and offered email addresses and phone numbers. It never fails to amaze me how tight our community is. We are friends, and family, for life.
Great Book I Just Read
Murder in the High Himalaya: Loyalty, Tragedy, and Escape from Tibet
by Jonathan Green
This is a rare book that provides multiple levels of reading, on history, ethics, exposé, culture, politics and an unforgettable story of a young girl’s perseverance, determination and tragic legacy. I love real life adventure and survival books, especially about mountain climbing and/or history, and also books about how one person can change the world. This book has it all. On September 30, 2006 a cruel and thoughtless murder of a 17-year-old Tibetan nun (just a girl truly) by Chinese border guards triggered an avalanche of scrutiny in the press, world agencies, political leaders–and in the consciences of the Western mountain climbers on a paid guided climb who watched in horror. Kelsang Namtso was trying to escape Tibet via the mountain Cho Oyu when she was gunned down in full view of climbers, one of whom videotaped it. The tape went viral—the first time human rights violations against the Tibetans had been filmed—and the rest is history. This book tells this amazing story in gripping and often exquisite prose (much like Jon Krakauer) and provides powerful parallel stories of Kelsang and the mountain climbers, which later intersect dramatically and make history (much like author Erik Larsen). You will be amazed at the courage of this 17-year-old, and at the response by those who witnessed her death. Green’s compelling narrative will teach you much about Tibet, how it has suffered under Chinese rule, and how the West has looked away until one lone video clip, still available on YouTube, shamed us into action. Green raises excellent questions that beg an inward look at our own souls, and portrays Tibetan lives without freedom that make us instantly cherish our own freedom. A must read. Four out of five stars.
A persistent question we are always asked is “What ever happened to gene therapy?” We used to write extensively about this subject when gene therapy was hot, but since the deaths of two young people in gene therapy trials unrelated to hemophilia, all gene therapy seems to have taken a slow and extremely cautious route. There instead seems to be great interest in creating new and less expensive ways to manufacture factor. We recently heard of a new biotech company in California, founded by a parent of a child with hemophilia, that is developing all therapies, which hints that these products one day will be lower in cost.
And the newswires announced this last week: GTC Biotherapeutics, a Massachusetts-based biotech company, held a webcast this morning from Monaco; the webcast will be available tomorrow through the company’s website. This company “develops, produces, and commercializes therapeutic proteins through transgenic animal technology.” This means literally milking animals for the desired protein that is developed through gene therapy and then expressed through the animal’s milk.
Like many, I feel a bit skeptical but according to GTC, in August 2006 its recombinant form of human antithrombin was approved by the European Commission for use in patients with hereditary antithrombin deficiency undergoing surgical procedures. This was the first approval anywhere in the world of a therapeutic protein produced from a transgenic animal. GTC has developed goats that have the human antithrombin gene linked to a milk-protein promoting gene so that they express this protein in their milk.
In 2006, GTC was granted a patent in the United States through 2021 for the production of any therapeutic protein in the milk of any transgenic mammal. And GTC has established a strategic collaboration with LFB Biotechnologies of France to jointly develop recombinant human factor VIIa as a potential treatment for hemophilia inhibitor hemophilia patients. This would be a direct competitor to NovoSeven, apparently. Although the article doesn’t directly state this, it implies that this recombinant FVIIa would be expressed by animals?
It bears watching, and we hope to bring more information about this through PEN and through HemaBlog. Watch the webcast yourself tomorrow at the GTC web site, www.gtc-bio.com.
HemaBlog Archives
Categories
LA Kelley Communications - You are leaving our site
You have clicked on one of our advertiser’s links. Our provision of a link to
any other website or location is for your convenience and does not signify
our endorsement of such other website or location or its contents.
Would you like to continue?
Download Now
Would you like to be added to our email list to continue to recieve future editions of PEN in PDF format?
