It’s New! Therapeutic! And Coming Soon!

Dr. Glenn Pierce
With a record-breaking 2,987 in attendance, NHF’s 69th annual meeting in Chicago on August 24-26, was the largest and most varied!
 
Two of my favorite speakers at NHF Annual Meetings and whose sessions I always seek out, are Glenn Pierce, MD, PhD and Steven Pipe, MD. And they did not disappoint! Although it would take an entire blog to list all of the accomplishments of these two highly respected individuals, suffice to say that they are both very knowledgeable about bleeding disorders in general and about clotting factors, novel treatments and gene therapy in particular. And they both share a relatively rare ability: they are able to explain complex medical topics to consumers in terms that we can understand (okay, mostly understand!)
 
In Dr. Pipe’s Friday morning session, “The Cure Horizon: Point/Counterpoint”, whom he co-hosted with Dr. Rebecca Kruse-Jarres, Pipe played the part of advocate for gene therapy and his counterpart advocated for “small molecules” (novel, non-factor treatments for preventing bleeds). Later that day Dr. Pierce gave the plenary session on “New Treatments and Gene Therapy.” Although both sessions covered some of the same information, they did so from different perspectives and it was beneficial to attend both.
 
Dr. Steven Pipe
Here’s a recap of the two talks regarding new therapies on the horizon. On the “small molecule” side there are three different approaches being investigated that can reduce bleeds without the use of factor. One therapy, emicizumab, or better known in the community as ACE910, is likely to be the first to market—and soon. ACE910 is a therapy for hemophilia A ,with or without inhibitors. It is a bi-specific antibody (meaning the antibody can grab two different factors at once) designed to mimic the function of factor VIII by bringing together factors IXa and X to initiate clotting. It is
administered weekly as a subcutaneous injection. Genentech’s ACE910 has been granted priority review by the FDA and their license application may be approved as soon as February 2018. (It was also mentioned that repeated doses of aPCC, a by-passing agent sometimes used by people with inhibitors, in conjunction with ACE910 can result in unwanted clotting.)
 
A second approach involves blocking the function of a player in the clotting cascade called tissue factor pathway inhibitor (or TFPI) that serves to check the clotting process so it does not runaway out of control. This therapy, called concizumab or anti-TFPI, is also an antibody and also administered subcutaneously. It blocks the function of TFPI and is effective in reducing bleeds in people with hemophilia A, B as well as those with inhibitors. Anti-TFPI has entered phase 2 clinical trials this summer.
 
The third approach uses genetic material that blocks a cell’s ability to produce antithrombin, which like TFPI, serves as a check on
coagulation. Called fitusiran, this agent interferes with the cell’s RNA involved in the production of antithrombin—in short, it prevents the cell from making antithrombin and restores a “balance” between the two parts of the clotting process: one that makes clots and the other that stops the clotting process. This agent is in phase 2 clinical trials.
 
All three of these novel hemophilia treatments were referred to as “disruptive therapies.” This is similar to the term “disruptive technologies,” which “refers to any enhanced or completely new technology that replaces and disrupts an existing technology, rendering it obsolete. It is designed to succeed similar technology that is already in use”1. Examples of disruptive technologies include DVRs, which displaced VHS recorders; PCs, which displaced both typewriters and mainframe computers; and laptops, which displaced desktop PCs and might soon find themselves displaced by tablets; and tablets which may be replaced by ever-larger and more powerful smart phones, which themselves have disrupted the telecommunications industry. The emerging small molecule therapies for hemophilia will be more convenient, last longer, be easier to administer and will likely be less expensive than clotting factor concentrates. They will upend the market for factor concentrates, which have been the mainstay treatment for hemophilia in developed countries since the late 1970s. And, of course, gene therapy is on the horizon, which will then disrupt the market for small molecule therapies for hemophilia.
 
And what about gene therapy? Both speakers mentioned significant advances made by two companies, Spark and BioMarin, which have been successful in converting individuals with severe hemophilia into mild hemophilia, with Spark reporting sustained factor VIII levels of 12% and 14% in two patients. These levels are high enough to prevent spontaneous bleeds. This brings up the question: what level of factor expression represents a cure? Should we wait until gene therapy can cure hemophilia by raising factor levels above 50%? And of course, the question of cost is forefront in everyone’s mind. These questions have yet to be answered.
The times they are a changin’! Never before have we had so many factor products on the market, with new factor products, as well as disruptive small molecules and gene therapy, still in development. What is certain is that, in the near future, hemophilia therapy will look dramatically different than it does today.
 
1. https://www.techopedia.com/definition/14341/disruptive-technology

NHF’s 69th Annual Meeting in Chicago

“Exploring the Next Frontier” was the theme for the 69th annual National Hemophilia Foundation meeting in the dazzling city of Chicago. A record-breaking 2,987 community members flocked to the Windy City (do you know why it’s called that?)—patients, treatment center staff, industry representatives and hemophilia organization advocates—to share stories, to educate, to network, and to learn.
Inside a blood vessel!

For me, it was my 25th annual meeting, and more like a huge family reunion. With so many friends from past meetings and local chapter meetings and correspondence, on top of all my new friends on Facebook, it was almost impossible to go from point A to point B without bumping into someone I knew!

Brian Andrews, chair of NHF, opened the weekend-long event Thursday evening by welcoming everyone; Val Bias, CEO, stressed inclusiveness and our diversity: individually he welcomed the VWD community, the FX, FI, FXIII, women with bleeding disorders (not VWD but hemophilia!) communities, who all stood up. Val then placed the focus on the National AIDS Memorial Grove, San Francisco, on which names of those with hemophilia lost to AIDS are carved. A touching video showed the memorial, with comments from community members, in particular Jeanne White-Ginder, whose son Ryan White, our own national hero, in 1982 put a tender young face to the scourge of hemophilia/AIDS by refusing to accept being ousted from his school. His stand led to a national movement to better understand the suffering of AIDS patients, the discrimination they faced and the erroneous fear that electrified Americans, most of whom believed you
could contract HIV just from a handshake.
 
It was a beautiful video, and Jeanne concluded it with a heartfelt, tearful speech about her love for our community. Val asked for donations, to raise $50,000 for the Memorial, and by the close of the conference, $41,000 had been raised!
 
The next few days were jam-packed with activities, educational sessions, and walks through the industry and nonprofit booths
downstairs, where consumers could play games, speak with reps, and pick up literature on products and services.
 
Our own Save One Life had a booth that actively received inquiries on how to sponsor a child with a bleeding disorder in a developing country.
 

The highlight of my visit was the Octapharma symposium Friday morning, showcasing the documentary trailer for “Bombardier Blood,” directed by Patrick James Lynch, who has hemophilia A. Patrick shared the incredible story of the making of the documentary—a project of which I was a part! I traveled to Nepal (visit #4) to introduce Patrick and his team to the Nepalese Hemophilia Society, and to watch as the team filmed Chris Bombardier (factor IX, from Denver) visit the treatment center, travel to patients’ homes, and attend a fun cultural evening before heading out to attempt to summit Mt. Everest. I also accompanied Chris, his wife Jess and photographer Rob Bradford, all the way to Everest Base Camp.
 
 
Although I was with them the week in Kathmandu, and then endured the rugged 9-day trek to base camp at 17,500 feet, and then shivered three days at base camp, with 1° temps at night, nothing, nothing stirred me as much as watching the documentary. The full impact of Chris’s sacrifices, the months of training, overcoming fears, and the pressure on this young man to succeed, hit me full force as we saw in six minutes scenes from Denver, from Nepal, patients, base camp… and Chris on the summit, talking through his oxygen mask, holding a banner on which was written the names of Nepalese patients with hemophilia. He did it for them; he did it for us.
Patrick J.Lynch, Laurie Kelley, Chris Bombardier

Over 360 people had permits to climbing Everest that season; 60 summited, including Chris; 10 died, including a world class alpinist, Ueli Steck. Chris risked his life to achieve something no one in history had done: being the first with hemophilia to summit Mt. Everest. Listening to Patrick, and seeing the beautiful trailer, we were all wiping away tears. The human heart has so much potential for courage, for sacrifice for our fellow humans, for overcoming fear and pain. Chris embodied all this.

I worried for the next speaker: how do you top that? But you know, Seth Rojhani, a young man from Denver, nailed it. His story was incredibly motivating and uplifting: being born with hemophilia, then losing your ability to walk after having a spinal bleed, and the surgeons severing your spine accidentally. But nothing has stopped Seth. He loved sports, and with the full support from his wonderful parents (who I am proud to say I know) he participated in many sports!
 
With his favorite basketball team the Denver Nuggets, Seth Rojhani went on to form “Rolling Denver Nuggets,” a basketball team for wheelchair participants. I loved when he shared his formula for success:

Seth Rojhani and Laurie Kelley
 
He stayed on a consistent prophy schedule; He rested until all injuries healed; He visited his HTC often. Seth received numerous athletic awards, including the Bronze medal for his team in the Maccabiah Games in Israel this past July. And he promptly pulled out the gleaming medal for the audience to see! Seth said, “Hemophilia is a speed bump, not an obstacle.” He also shared that his father, Ira, told him, “Think positive and good things will happen.” His belief in this way of thinking has never let him down.
 
When asked of the three participants—Patrick, Chris and Seth—what was the biggest challenge they faced in life, Patrick mentioned losing his brother Adam. His brother never identified with the hemophilia community, and felt isolated, alone. He might as well lived on the outskirts of Nepal, exclaimed Patrick, without factor or comprehensive care. Patrick’s greatest
challenge is overcoming the loss of his brother. Chris’s? Not Mt. Everest but needles! Chris has a needle phobia! And Seth? Being told no so much in his life.
 
The speakers deservedly received a standing ovation for their incredible stories and work. The three days were filled with symposia and sessions. For first time, the LGBT community had their own session, led by our own (New England-based) Justin Levesque. And I am proud to say that PEN was the first publication in our community to publish an article about the community needs, also written by Justin. 
 
Women with bleeding disorder and those with VWD were also given lots of meeting and air time. You can see a big shift in mindsets this year about inclusion in our community. Those on the fringe are now being heard.
 
There were also sessions for siblings and one for men only; sessions about pain management, addiction, and gene therapy. The only bad thing about NHF’s Annual meeting is that there is so much to see, hear and do! I couldn’t take in everything unfortunately.
 
The event ended with a stunning visit to the world famous Field Museum, sponsored by Bioverativ, where families could see the wonders of nature and natural history. My favorite display are “The Ghost and the Darkness,” two man-eating lions from Tsavo, Kenya, which were killed in 1898 after they had killed many workers on the railroad. A Hollywood movie starring Val Kilmer and Michael Douglas tells a somewhat fictional version of the story. It’s a good story but better to see them for real at the museum.