Two new studies could pave the way to major changes in how doctors treat severe cases of hemophilia — a rare genetic disorder that can cause uncontrolled bleeding.
Both studies tackle a key challenge: Up to one-third of children with severe hemophilia develop antibodies against the standard therapy.
But one study highlights the value of an old therapy, while the other shows promising early results with an experimental drug.
Experts said both should stir discussion among doctors, patients and parents who deal with hemophilia. But they were especially hopeful about the new drug, known as emicizumab.
In the United States, about 20,000 people — mostly boys and men — are living with hemophilia, according to the U.S. Centers for Disease Control and Prevention.
The disorder is caused by a defect in one of the genes that controls proteins needed for normal blood clotting. Most people have hemophilia A, which means they lack a protein called factor VIII. In severe cases, they have little to no factor VIII in their blood.
The standard treatment is to replace the protein through intravenous infusions done at home.
Years ago, that replacement protein came exclusively from donor blood. “That worked well until the 1980s and the HIV epidemic,” said Dr. Christopher Walsh, director of the hemophilia program at Mount Sinai Hospital, in New York City.
Between the late 1970s and mid-1980s, half of Americans with hemophilia became infected with HIV through contaminated blood products, according to the National Hemophilia Foundation.
That led to the development of genetically engineered “recombinant” factor VIII.
In the United States and other wealthy countries, most patients receive recombinant factor VIII, Walsh said.
In general, the therapy works well, he noted. But a major problem is that some children develop antibodies against the replacement factor VIII soon after they begin treatment.
One question has been whether the source of the factor VIII — donor blood or DNA technology — makes a difference, explained Dr. Donna DiMichele, of the U.S. National Heart, Lung, and Blood Institute.
One of the new studies was designed to answer that question, said DiMichele, who wrote an editorial published with the findings.
An international team of researchers randomly assigned 264 young children newly diagnosed with severe hemophilia to start replacement therapy with either blood-derived or recombinant factor VIII.
Overall, 37 percent of children on the recombinant therapy developed antibodies. That compared with 23 percent of kids on blood-based therapy.
Lead researcher Dr. Flora Peyvandi said the findings suggest blood-derived factor VIII is the “better choice” for children beginning therapy.
The findings do not apply to patients who’ve been on therapy for a while, according to Peyvandi, of the University of Milan, in Italy.
If a child is going to develop antibodies, that usually happens within the first 50 infusions, she explained.
But Walsh and DiMichele expressed doubts about whether blood-derived factor VIII is better for children just beginning therapy.
For one, DiMichele said, the risk of developing antibodies might be lower, but it’s still significant.
Walsh agreed, and also pointed to safety concerns.
The blood supply is thoroughly tested, and considered very low-risk. “But,” Walsh said, “anytime a ‘new’ virus comes out that could be spread through blood transfusions — like the Zika virus — patients worry. You’re always looking over your shoulder.”
He and DiMichele both predicted that doctors will vary in their opinions, and their advice to patients.
Meanwhile, the emicizumab study suggests an entirely different solution to the antibody problem, Walsh said.
The drug is a lab-generated antibody that “mimics” the form of factor VIII, which allows it to do the protein’s job. It’s designed, in part, to get around the problem of factor VIII antibodies.
DiMichele called the drug “ingenious.”
“The fact that they could even do this is remarkable,” she said.
The new trial tested the drug in just 18 patients with severe hemophilia. But over three months, 72 percent had no bleeding episodes. And it was just as effective in patients who’d developed antibodies to factor VIII as those who were antibody-free.
The study was sponsored by Japanese drug maker Chugai Pharmaceutical, one of the companies developing emicizumab. Larger trials are underway, according to the company.
Emicizumab is easier to take than factor VIII replacement. It requires one weekly injection, versus several IV infusions per week. Young children on factor VIII often need a catheter device implanted under the skin to allow the frequent infusions.
The new findings “should be very exciting for patients and parents,” DiMichele said. “But we still need much more information.”
Researchers need to show the drug is effective and safe in the longer term, she said. It’s also unclear whether it not only prevents bleeding episodes, but treats them when they do happen — as factor VIII replacement can.
“Does this represent a sea change?” Walsh said. “We’ll see.”
The ultimate hope, he noted, is to use gene therapy to potentially cure hemophilia. Researchers are already working on it, he added.
Both studies were published May 26 in the New England Journal of Medicine.
The U.S. Centers for Disease Control and Prevention has more on hemophilia.
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