The US Food and Drug Administration (FDA) approved Hemgenix (etranacogene dezaparvovec) gene therapy for the treatment of adults with hemophilia B (congenital factor 9 deficiency) who currently use factor 9 prophylaxis therapy; have current or historical life-threatening hemorrhage; or have repeated, serious spontaneous bleeding episodes.
Despite advancements in the treatment of hemophilia, the prevention and treatment of bleeding episodes can adversely impact individuals’ quality of life, said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, in a press release. “Today’s approval provides a new treatment option for patients with hemophilia B and represents important progress in the development of innovative therapies for those experiencing a high burden of disease associated with this form of hemophilia,” he said.
The approval could fundamentally transform the treatment paradigm for this lifelong condition, said Steven Pipe, MD, professor at the University of Michigan and a lead investigator in the HOPE-B study, in a press release from the company. “As a clinician, I look forward to being able to provide a new treatment option that may help patients treated with Hemgenix become free from the regular infusion schedule that many people living with hemophilia B rely on to protect them from the debilitating effects of the condition ,” he said.
Although there are still things we are learning about Hemgenix for hemophilia B, especially in the long term, the data that we have so far has been very encouraging, says Nigel Key, MBChB, professor at UNC School of Medicine and director of the UNC hemophilia and thrombosis center in Chapel Hill, North Carolina.
UNC was one of a number of medical centers around the world who contributed patients to the clinical trial, and Dr. Key was an investigator in the trials for Hemgenix.
“This can completely change a patient’s life in many ways if they have a successful outcome with the therapy,” says Key.
Hemophilia B Can Put a Person at Risk for Life-Threatening Bleeding
Hemophilia B (HB) is a genetic bleeding disorder resulting from missing or insufficient levels of blood clotting factor 9, a protein needed to produce blood clots to stop bleeding. This puts a person at risk for prolonged and life-threatening bleeding after an injury, surgery, or dental procedure.
in severe cases, bleeding episodes can occur spontaneously without a clear cause. More prolonged bleeding episodes can lead to serious complications, such as bleeding into joints, muscles, or internal organs, including the brain.
Hemophilia B mostly affects men, and its prevalence in the population is about 1 in 40,000; HB represents about 15 percent of patients with hemophilia.
Hemgenix Could Offer Patients ‘One and Done’ Treatment for Hemophilia B
People with severe hemophilia B typically undergo replacement protein therapies two to three times a week through their entire lifetime to prevent bleeding episodes, per Hematology and Oncology Associates of CNY. In contrast, Hemgenix only needs to be delivered once as an IV infusion.
How it works: Hemgenix uses AAV5, a noninfectious viral vector, called an adeno-associated virus (AAV), to carry genetic instructions (DNA) to the patient’s liver, where they remain in the target cells but generally do not become a part of a person’s own DNA.
Ideally, the therapy allows the body to produce the missing clotting factor on its own, which would reduce or eliminate the need for injections with clotting factor, as well as reduce the number of bleeds.
Hemgenix Increased Blood Levels of Clotting Proteins and Reduced the Rate of Annual Bleeds
Hemgenix was evaluated in two studies of adult men 18 to 75 years of age with severe or moderately severe hemophilia B. Effectiveness was measured based on decreases in the men’s annualized bleeding rate (ABR).
In one study, which had 54 participants, the subjects had increases in factor 9 activity levels, a decreased need for routine factor 9 replacement prophylaxis, and a 54 percent reduction in ABR compared with baseline.
Hemgenix allowed patients to produce mean factor 9 activity of 39 percent at six months and 36.7 percent at 24 months post infusion.
Normal plasma levels of factor 9 are between 50 percent and 150 percent, and 30 to 40 percent would be considered only mild hemophilia, according to the National Hemophilia Foundation. These participants started out at 1 percent, and so the therapy puts them in a completely different — and much better — situation in terms of risk of bleeding and frequency of bleeding, says Key. “Basically, patients at that level would require surgery or major injury to bleed,” he says.
But there are patients whose response to the therapy aren’t as robust — more like 5 to 10 percent — and there are also those who have a very strong response — up to 110 percent — so that’s a little unpredictable, says Key. “There’s still research to be done to understand some of these issues, person-to-person variation being one of them,” he says.
In the ongoing clinical trial, Hemgenix reduced the rate of annual bleeds and 94 percent of participants discontinued taking their prophylactic therapy and remained prophylaxis-free.
It appears the efficacy of Hemgenix will continue for at least 10 years after it is administered, and potentially last for decades, but exactly how long is something we’ll have to wait to find out, says Key.
What Were the Most Common Side Effects of Hemgenix in Clinical Trials?
Gene therapy for hemophilia has been in development for 20 years, and from what has been seen so far, Hemgenix has a reasonable efficacy and safety profile, says Key.
In clinical trials, the most common side effects reported in more than 5 percent of patients were liver enzyme elevations, headache, elevated levels of a certain blood enzyme, flu-like symptoms, infusion-related reactions, fatigue, nausea, and feeling unwell.
Other side effects may be possible, according to the researchers.
Who Will Be Able to Receive Hemgenix and When Will It Be Available?
“CSL Behring will make Hemgenix available for eligible people with hemophilia B as soon as possible, but we do not have specifics on timing,” says James Freeman, senior director of global commercial communications for CSL Behring.
Hemgenix is indicated for adults with hemophilia B who currently use factor 9 prophylaxis therapy or have current or historical life-threatening bleeding or have repeated, serious spontaneous bleeding episodes. Before Hemgenix is administered, the candidate is tested for factor 9 inhibitors; if they test positive, they are not eligible for the therapy.
How Much Will Hemgenix Cost?
The list price of Hemgenix is set at $3.5 million, says Freeman. “We are confident this price point will generate significant cost savings for the overall healthcare system and significantly lower the economic burden of hemophilia B by reducing annual bleed rates, reducing or eliminating prophylactic therapy, and generating elevated [factor 9] levels that last for years,” he says.
“This price was determined with consideration of the clinical, societal, economic, and innovative value represented by this novel gene therapy and was designed to support patient access to this new treatment paradigm,” says Freeman.
Hemophilia B is a very expensive disease to treat — over many years, treatment with Hemgenix may prove to be a good investment, says Key.
The cost of therapy for people with severe and moderately severe HB can run $300,000 per year or more, and over $20 million over the course of a lifetime, according to a study published in 2021 in the Journal of Medical Economics.
Given that hemophilia B is a rare disease affecting only about 6,000 individuals in the United States, with an even smaller fraction of that population requiring factor 9 prophylaxis therapy, only a portion of people living with hemophilia B will be eligible to receive Hemgenix, says Freeman .
“This will mean the overall budget impact of Hemgenix on the healthcare systems will be very small relative to overall budgets,” he says.
Hemgenix Connect Offers Support to People With Hemophilia B Who Are Interested in Gene Therapy
CSL plans to launch HEMGENIX Connect, which offers a suite of services to support those with hemophilia B who are interested in gene therapy, says Freeman. “People living with hemophilia B who have spoken with their doctor can enroll in the HEMGENIX Connect program where they will be assigned a dedicated team, including a Patient Resource Navigator and CSL Case Manager, who will be their point of contact for educational resources and support ,” he says.
The program offers information about gene therapy as well as the different stages of the treatment journey, from exploration to insurance to support services.