After gene therapy, hemophilia B patients maintain near-normal levels of clotting factor

December 3, 2016

Researchers are reporting the highest and most sustained levels to date of the essential blood-clotting factor IX in patients with the inherited bleeding disorder hemophilia B. After receiving a single dose of an experimental gene therapy in a clinical trial, patients with hemophilia produced near-normal levels of clotting factor IX, allowing them to stop clotting factor infusions and to pursue normal activities of daily life without disabling bleeding episodes.

Lindsey A. George, MD, a hematologist at Children's Hospital of Philadelphia (CHOP) is the lead investigator of the phase 1/2 clinical trial sponsored by Spark Therapeutics, Inc. and Pfizer, Inc. The American Society of Hematology (ASH) today highlighted updated findings from that trial in a press conference during its annual meeting in San Diego. George will present those study results tomorrow at an ASH plenary scientific session.

Katherine High, MD, a senior author of the study and Spark Therapeutics's president and chief scientific officer, described the updated interim trial data at today's press conference. The clinical trial of nine adult hemophilia B patients, aged 18 to 52 years, used a single dose of a gene therapy product engineered to enter patients' liver cells and direct the production of the blood clotting factor that they lack.

George notes, "Our goal in this trial was to evaluate the safety of the gene therapy product and secondarily, to determine if we could achieve levels of factor IX that could decrease bleeding events in patients." She added, "These patients have a severe or moderate level of hemophilia, with baseline clotting factor level less than or equal to 2 percent of levels in healthy people. In current treatment, patients with hemophilia give themselves intravenous doses of factor IX up to a couple times a week. While generally effective, factor levels fluctuate, and patients may suffer painful, disabling joint bleeds when their levels drop. Such a regimen requires significant planning of daily activities."

In the current trial, said George, the patients maintained factor levels of approximately 30 percent, enough to lift them out of the severe category. "At these new levels, hemophilia patients do not typically need to self-treat with factor to avoid bleeding events," she said, adding, "This represents a potential dramatic improvement in their quality of life and a shift in the way we think about treating hemophilia." A factor level of 30 percent is near-normal, she added, and patients would be expected to experience bleeding only in the event of major trauma or surgery.

One subject self-infused two days after receiving the gene therapy vector. Beyond this, no patients had any bleeding events or required factor for any reason. With significant reduction in bleeding events and factor use, six of the first seven patients reported increased physical activity and all reported improved quality of life. Two additional patients received the gene therapy product too recently to determine quality-of-life measures.

Previous hemophilia gene therapy have been frustrated by an immune response to the gene therapy product that limited the success of the therapy. In the current trial, two patients experienced an immune response to the gene therapy that did not result in safety concerns, and were treated with steroids. The patients are still undergoing treatment but have maintained factor IX activity without bleeding.

George reported that she is cautiously optimistic, acknowledging that this trial is a small study, with a short follow-up period as yet. However, as the researchers continue to monitor in the current trial, next steps will be to discuss with the U.S. Food and Drug Administration the outlines of a larger, phase 3 clinical trial. No gene therapies for any genetic diseases have yet been approved for clinical use in the U.S.

Formerly a research leader at CHOP, High pursued groundbreaking preclinical investigations in hemophilia B gene therapy and provided scientific expertise to previous trials in hemophilia and other genetic disorders at CHOP before moving to Spark Therapeutics, which was spun off from CHOP in 2013. CHOP maintains a financial interest in the company.

Explore further: In crafting new treatments for hemophilia, a 'less is more' approach

Related Stories

In crafting new treatments for hemophilia, a 'less is more' approach

October 17, 2016
Hematology researchers have found that blocking the role of a common protein may offer unexpected benefits for patients with the inherited bleeding disorder hemophilia A. The finding offers potential for developing both gene ...

To treat one rare blood disorder, scientists exploit another

October 27, 2016
For the nearly 400,000 individuals around the world with hemophilia A and hemophilia B—rare blood disorders that impair a person's ability to form clots to stop bleeding—relief may someday come from a treatment with similarities ...

Gene therapy for rare bleeding disorder achieves proof-of-concept

January 20, 2016
Hematology researchers have used a single injection of gene therapy to correct a rare bleeding disorder, factor VII deficiency, in dogs. This success in large animals holds considerable potential for a safe, effective and ...

Scientists use CRISPR for first time to correct clotting in newborn and adult mice

November 30, 2016
CRISPR/Cas9, a powerful genome editing tool, is showing promise for efficient correction of disease-causing mutations. For the first time, researchers from the Perelman School of Medicine at the University of Pennsylvania ...

Long lasting anti-hemophilia factor safe in kids

April 24, 2015
Children with hemophilia A require three to four infusions each week to prevent bleeding episodes, chronic pain and joint damage. The effect on quality of life can be significant, due to time and discomfort associated with ...

Study bolsters 'turbocharged' protein as a promising tool in hemophilia gene therapy

March 12, 2015
Using gene therapy to produce a mutant human protein with unusually high blood-clotting power, scientists have successfully treated dogs with the bleeding disorder hemophilia, without triggering an unwanted immune response. ...

Recommended for you

3-D printed microfibers could provide structure for artificially grown body parts

December 12, 2017
Much as a frame provides structural support for a house and the chassis provides strength and shape for a car, a team of Penn State engineers believe they have a way to create the structural framework for growing living tissue ...

Potassium is critical to circadian rhythms in human red blood cells

December 12, 2017
An innovative new study from the University of Surrey and Cambridge's MRC Laboratory of Molecular Biology, published in the prestigious journal Nature Communications, has uncovered the secrets of the circadian rhythms in ...

Time of day affects severity of autoimmune disease

December 12, 2017
Insights into how the body clock and time of day influence immune responses are revealed today in a study published in leading international journal Nature Communications. Understanding the effect of the interplay between ...

Team identifies DNA element that may cause rare movement disorder

December 11, 2017
A team of Massachusetts General Hospital (MGH) researchers has identified a specific genetic change that may be the cause of a rare but severe neurological disorder called X-linked dystonia parkinsonism (XDP). Occurring only ...

Protein Daple coordinates single-cell and organ-wide directionality in the inner ear

December 11, 2017
Humans inherited the capacity to hear sounds thanks to structures that evolved millions of years ago. Sensory "hair cells" in the inner ear have the amazing ability to convert sound waves into electrical signals and transmit ...

Gene therapy improves immunity in babies with 'bubble boy' disease

December 9, 2017
Early evidence suggests that gene therapy developed at St. Jude Children's Research Hospital will lead to broad protection for infants with the devastating immune disorder X-linked severe combined immunodeficiency disorder. ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.