Gene Therapy Helps Father With Hemophilia Live an Active Life

Julian hasn’t had a bleed or an infusion since his gene therapy for severe hemophilia B 

Julian Ross, age 41, has lived through several revolutionary shifts in the way hemophilia is treated. Julian has hemophilia, a hereditary condition that makes it harder for blood to clot. People with hemophilia are missing one clotting factor, or protein that helps blood clot.

In the 1980s, when Julian was born, there were no treatments available for people with hemophilia, leading to crippling joint disease. The first therapies, which involved clotting factors made from plasma, were sometimes contaminated with HIV or hepatitis C.

“The hemophilia community has gone through so much,” said May Chien, MD, a pediatric and adult hematologist at Stanford Medicine Children’s Health. “It was only within Julian’s lifetime that we were able to give factor, and that still requires infusions roughly once a week. On top of that, many people still have joint bleeds even with that preventative therapy.”

Julian was born and raised in the Bay Area and is a lifelong patient of Stanford’s Hemophilia Treatment Center, which includes pediatric and adult hematologists to follow patients for life. These days, he lives in Oakland and works as a public defender.

“When I met Julian, he was infusing factor twice a week,” said Caroline Berube, MD, who has been Julian’s primary hematologist since 2015. “He showed up in clinic with his right elbow all wrapped up from an acute bleed. A few years later, clotting factor products improved and he was able to switch to infusing once a week, and more recently switched to a factor that he only had to infuse once every other week. He really went through the whole story of a patient with hemophilia B.”

Now, gene therapy promises to bring an end to joint bleeds—and weekly infusions—for adults with severe hemophilia B, like Julian.

Until a few years ago, Julian was able to exercise and remain active without significant bleeding as long as he took his factor product once every two weeks or so. But as he got older, Julian started having difficulty giving himself factor injections into his overworked veins and started experiencing more bleeding, especially in his right elbow and right ankle.

“It just felt like my body was getting weaker,” he said. “It was also very frustrating to have to stick myself four or five times every time I had to give myself factor.”

Julian said having a bleed is like a having a balloon inside your joint—it severely limits mobility. Bleeds also cause significant pain and can lead to long-term joint damage.

Julian recalled getting two back-to-back bleeds that prevented him from caring for his then-newborn son.

“With my elbow bleed, I couldn’t carry my son, and then I was just walking and got a bleed in my right ankle, so I was limited in two different joints,” he said. “I felt like I couldn’t really help at all, that I was essentially another burden.”

Soon after that, Julian met with Dr. Berube for his annual checkup. She mentioned that a gene therapy for people with severe hemophilia B, Hemgenix, had just been approved by the U.S. Food and Drug Administration. Dr. Berube said Julian would be a good fit for the new therapy if he wanted to try it. Julian immediately said yes.

Stanford has run gene therapy clinical trials, so a team of experienced doctors, nurses, and pharmacists got to work. The procedure itself was a daylong infusion, done at the outpatient Infusion Center at Lucile Packard Children’s Hospital Stanford.

“It was very anticlimactic for him—he just sat in a chair and got an infusion, while all of us chewed our nails. He just sailed through with no side effects,” said Dr. Chien. 

Then came the wait to see if the therapy would work as planned. People with hemophilia B are missing a factor called factor IX (9). Hemgenix is a onetime gene therapy that delivers a functional copy of the factor IX gene to the liver. Clotting factors are naturally produced in the liver, so the working copy of the factor 9 gene is released into the liver’s cells, and the liver starts to make factor IX. This F9 gene therapy has its roots in lab research conducted in the 1990s by investigators at Stanford that led to clinical trials at Stanford and other hospitals around the world.

Julian started with less than 1% of the normal factor IX level in his blood. The goal of the gene therapy was to get his factor IX levels high enough to prevent bleeds and avoid the need for regular infusions.

Julian came in for weekly blood tests for three months to check his factor levels. At first, his factor levels were rising more slowly than expected, making it hard to tell if the treatment was working.

“I was disheartened at first, but I told myself, ‘Julian, your body feels great, that’s all that matters,’” he said.

Eventually, Julian was able to reach factor IX levels in the 30s (as a percent of normal), and those levels have persisted for more than a year after treatment.

“For gene therapy for hemophilia B, the long-term data looks very good, and it looks like the factor level is durable,” Dr. Chien said. “It took a lot of trust on Julian’s part; we only have so many years of data, since this is a new therapy, so he was very brave to participate.”

Gene therapy has so far been less successful in people with hemophilia A, who require a working copy of the factor 8 (F8) gene. Researchers are working to identify new ways to increase the durability of the new factor 8 gene. Meanwhile, other non-gene therapy approaches for people with hemophilia A have become available.

Researchers are also currently testing an approach to gene therapy for hemophilia B that may potentially open the treatment up to children. Hemgenix is currently only available for people 18 and older, but a new approach that uses CRISPR gene editing hopes to change that.

“The reason the current gene therapy is only available to adults is that we have to wait until the liver reaches its adult size,” said Dr. Berube. “That’s because as the child’s liver grows and the cells divide, the cells with the working factor 9 gene may get too diluted, so enough factor IX won’t be produced in the long term. In an ongoing clinical trial, we’re trying to insert the working gene in a different way to hopefully get better long-term expression of that gene.”

Julian and his wife recently welcomed their second child, and Julian can be more active with his kids without worrying about getting a bleed.

“After gene therapy, I haven’t had anything that even resembles a bleed,” he said. “I don’t have to worry about bumping into something wrong or carrying my kids. And it’s such a relief to not have the anxiety that came with giving myself factor and wondering if my veins would work.”

Once his children are older, Julian is looking forward to returning to a camp for people with hemophilia that he has attended since he was a kid.

“I had always thought that having hemophilia is part of my identity, and when I got the gene therapy, I worried, ‘Will I feel like I’m not part of that community?’” said Julian. “But I don’t have those thoughts now. I still have hemophilia; it’s just very, very mild now versus very severe.”

Within the hemophilia community, Julian hopes to be a resource to anyone considering gene therapy.

“It’s a total game-changer,” he said. “My body feels a lot healthier and stronger.”