Experimental Gene Therapy for Hemophilia B: Bill’s Story

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Across the span of 52-year-old Bill’s life, he has experienced the entire progression of treatment options for hemophilia B, the bleeding disorder he was born with. For the first few years of his life, there was almost nothing that could be done. Then treatments became available, at first taking up a great deal of Bill’s time, then becoming somewhat less of a burden over the years. In 2017, an experimental, potentially curative gene therapy for hemophilia B that was developed at CHOP became available through a clinical trial. Bill received this game-changing therapy five years ago, transforming his life by severely reducing his need for any treatment.

Experimental Gene Therapy for Hemophilia B: Bill’s Story Most people with hemophilia B have an inherited gene mutation that impairs their ability to produce normal levels of a blood clotting factor called factor IX, while others like Bill got the disease from a spontaneous gene mutation. Without this clotting factor, they can experience debilitating or life-threatening bleeding, either caused by an injury or occurring spontaneously. Routine activities have the potential to cause prolonged bleeding, externally or internally. Internal bleeding often involves the joints and muscles.

Bill was discovered to have hemophilia B shortly after he was born. His parents were “scared to death,” he says. “In the 1970s, hemophilia care almost didn’t exist. Got a bleed? You’d stick them in ice water. If you bled enough, they would replace the lost volume with whole blood.” But whole blood wasn’t very effective, because it does not contain sufficient quantities of clotting factor IX to make a major difference.

Bill remembers once, when he was 7 or 8, he had a bleeding episode while his family was driving to his grandparents’ house for Christmas. “My parents were staying at a hotel with a pool, so they asked if I could get in the pool to get the swelling down. The hotel manager thought we were nuts!”

There was nothing Bill could do but accept life with hemophilia: “I just worked with it and moved on.”

The development of plasma-derived clotting factor

Experimental Gene Therapy for Hemophilia B: Bill’s Story In the 1970s, clotting factors derived from plasma became available. At first, Bill needed to go to a hospital to get the treatment. “This required a 45-minute ride to the hospital in Baltimore four or five times a week, and the infusion took a couple hours.” Eventually, the hospital developed a home treatment program so constant visits to Baltimore weren’t necessary. For a while, this still meant being hooked up to an IV, but eventually the factor could be administered with a syringe. “The syringe method only took a few minutes, but I still needed it two or three times a week.” The next treatment development was long-acting factor that was meant to last 10 days, but Bill rarely could go that long without needing a supplemental boost.

His parents encouraged him to build up muscle around his joints. “I was constantly in physical therapy as a kid,” he says. “In high school, I took weight training instead of gym.” He tried to not let the disease limit his activities — “Much to my doctor’s chagrin,” he says with a laugh. “I’d have a bleed, get treated with factor, be off my feet for a couple days, and that was that.”

This was Bill’s reality for nearly 50 years. He grew up, held fairly physical jobs including running a lumber yard and working on a survey crew, then got a career as a structural engineering designer, had a family, all while needing factor IX every week or so.

Increasing the level of clotting factor

Periodically, Bill would do some internet searching to see what was happening in the field. That’s how he came across an item about an experimental gene therapy trial being conducted at Children's Hospital of Philadelphia (CHOP).

Gene therapy for hemophilia B uses a vehicle called a vector virus to deliver a functional gene to replace or do the work of the hemophilia patient’s own defective gene, leading to high enough clotting factor activity to protect against bleeding. The goal is to lessen bleeding, ideally for the rest of a person’s lifetime.

Bill emailed, inquiring about the trial. When a response arrived, asking if he was interested in participating, his answer was, “Hell, yes!”

He discussed the details with CHOP hematologist Lindsey George, MD, a world-renowned expert in gene therapy for hemophilia who was leading the trial at CHOP. Dr. George also spoke with Bill’s physicians, then Bill enrolled in the trial.

This gene therapy is administered using a single infusion — and it changed everything for Bill. Shortly after the infusion, he injured his ankle and needed a precautionary infusion of factor. “After that, I went more than a year without needing factor.” Ever since, the treatments that had been so prevalent his entire life receded from his thoughts. “I could pretty much forget about them.”

Although he had liked to say that hemophilia didn’t limit his activities, “It did lower my expectations a bit,” he admits.

The gene therapy has changed what I can do.

One of his hobbies is restoring antique and classic cars, and after being on his feet all day at a car show, he used to be unable to walk the next day. “That has gone away. Maybe at worst I’ll throw an ice pack on my ankle now.” He’s also taken up Taekwondo with his son.

CHOP recently launched the Novel Therapeutics for Bleeding Disorders (NoT Bleeding) Program to help more people like Bill. This program combines CHOP’s established clinical expertise in hemophilia gene therapy and management of bleeding disorders with the team’s research strengths.

Before the gene therapy, Bill’s factor IX level had been less than 1% of normal value, and his disease was considered to be “severe.” After the therapy, it’s at about 25%, and he is essentially a “mild” hemophiliac. He sums up his experience in one simple statement: 

It’s been life-changing.