Since 2010, the Bleeding and Clotting Disorders Institute (BCDI) has been serving patients of downstate Illinois. Located at the corner of Northmoor Road and Knoxville Avenue in Peoria, IL, BCDI is the only nonprofit, federally funded Hemophilia Treatment Center (HTC) of Excellence in the state of Illinois outside of Chicago. Among many accolades, BCDI is recognized as a worldwide leader in the bleeding and clotting disorders community with contributions including authoring over 250 publications, many of which resulted in some of the most widely used treatments and strategies for this population worldwide.
March is an important time at BCDI, celebrating and raising awareness for Bleeding Disorders Awareness Month. One of BCDI’s mission goals is to provide top-tier education and research for our community. In regards of innovation and the future of the HTC model, one topic has the entire community buzzing: gene therapy. Gene therapy for hemophilia patients has been on the horizon for more than two decades, and major scientific and medical developments have led to a gene therapy product for hemophilia officially hitting the market. The topic can be quite polarizing and confusing, but BCDI is here to explain what gene therapy is, who may benefit from gene therapy, along with other thoughts and concerns.
What Is Gene Therapy?
Gene therapy is the process of treating a genetic disorder or disease by providing persons with working copies of the gene to correct their condition. The concepts of gene therapy have been around 60-plus years, initially founded during the 1960s and early 1970s. However, the first approved gene therapy procedure was conducted in 1990 on a patient with severe combined immunodeficiency. Simply put, gene therapy is a treatment where new working genes are introduced into a person’s cells to correct a deficiency.
In respects to the bleeding disorder community, gene therapy strategies for hemophilia are blossoming, where new genes may give the body instructions on how to make clotting factor. In gene therapy, a working gene is carried into the liver cells of a person with hemophilia. Once the working gene reaches the cells, they should begin producing the missing factor. Currently, gene therapy focused on treating hemophilia uses a viral vector, which is a synthetic virus capsule that has no illness-causing material. It is used as a carrier to bring the new, working genes into a person’s cells.
The majority of gene therapy products for hemophilia A and B are currently being studied in clinical trials to determine how well they work and how safe they are. There are several factors and restrictions on who is eligible to participate in these types of studies: males aged 18 and over with severe hemophilia A or B (factor levels of less than one percent), have no evidence of hepatitis or liver dysfunction and are otherwise healthy (no history of cancer, diabetes, heart disease, etc.). Patients under the age of 18 and women with hemophilia have not been included in these clinical trials, but it is expected that the treatment will soon be studied in these populations.
Clinical trial studies show that patients with hemophilia that undergo gene therapy have varied outcomes. Some may see their factor levels increase (and in some cases to normal levels), while others may also be able to avoid factor infusions for longer periods of time. However, there are also significant risks associated with gene therapy, including strong immune system reactions, liver enzyme elevations, and flu-like symptoms. Every patient that receives gene therapy may have different results and may reach higher/lower factor levels than others.
Gene Therapy Options
As of February 2023, there is only one gene therapy product that is available on the market and approved for use in the hemophilia community. In November 2022, the U.S. Food and Drug Administration approved the first adeno-associated virus vector-based gene therapy for the treatment of adults with Hemophilia B. The FDA approval provides a new treatment option for patients with Hemophilia B and acts as a landmark in progress for the development of innovative therapies within the hemophilia community.
Hemophilia B is an inherited disorder characterized by bleeding due to a partial or complete deficiency of factor IX—a coagulation protein that is made in the liver and is necessary to help the blood form clots to stop bleeding. Individuals with severe and moderately severe hemophilia B may have spontaneous and prolonged bleeding episodes, which leads to internal organs and joint complications. Current therapies include lifelong and regular factor replacement to treat or prevent bleeding, representing a burden for some affected by the disorder.
The gene therapy design is a one-time treatment given through one intravenous infusion. It uses a modified adeno-associated virus to deliver a gene to the liver; once the gene reaches the liver, it is expressed and cells start making factor IX. In an ideal outcome, this virus has been modified, and the illness-causing material has been removed.
Two clinical trials have shown that the Hemophilia B gene therapy treatment is effective, with an increase in factor IX levels (mean factor IX activity 39 IU/dL and 36.9 IU/dL 6 and 18 months after the infusion). The exciting part is that 98 percent of the patients stopped IX prophylaxis completely, reducing overall factor IX consumption by 97 percent and there was a 54 percent reduction in annual bleeding rate compared to baseline. The most common adverse reactions reported include liver enzyme elevations, headaches, mild infusion-related reactions, and flu-like symptoms.
There are many other gene therapy products that are in the works for a variety of blood disorders that are in various steps of the clinical trial and approval process. Looking at Hemophilia A specifically, there are gene therapy options that are gaining momentum but are still awaiting FDA approval and on the cusp of a breakthrough.
Gene Therapy at BCDI
The Bleeding and Clotting Disorders Institute is equipped to be an administration site for gene therapy. In July 2021, BCDI open a brand-new, state-of-the-art 22,000 square foot facility in Peoria. Within this new location, BCDI has the proper space and resources to host gene therapy procedures.
BCDI has its own cleanroom—a controlled operating environment which offers specialized control, cleanliness, and equipment that is necessary in the high-risk gene therapy process. The use of a cleanroom for gene therapies ensures treatment viability and patient safety.
BCDI also provides comprehensive, specialized laboratory services, which can be tailored to any patient’s needs. BCDI has a dedicated infusion suite which is capable of doing on-site infusions for gene therapy. The Dills Family Foundation Center for Research at BCDI is committed to bringing the best research programs and education to our patient population, allowing our patients to receive cutting edge treatments while staying in the comfort of their own area.
BCDI is one of the few HTCs nationwide that has the necessary space to administer gene therapy infusions. With state-of-the-art facilities, a dedicated staff with a wealth of experience, and the resources to potentially administer gene therapy to patients, BCDI continues to be a leader within the HTC community.
The Bleeding and Clotting Disorders Institute is committed to providing the highest quality of care to persons with bleeding, blood clotting, and other blood disorders. If you would like to learn more about the gene therapy process or solutions, please reach out to BCDI by calling (309) 692-5337 or emailing info@ilbcdi.org.