Early Trial Offers New Hope for People With Hemophilia

Researchers may have found a way for people with severe hemophilia to take their standard treatment less often, if the results of an early trial pan out.

In what experts called a feat of bioengineering, scientists were able to create a "fusion protein" that may extend the interval between treatments for hemophilia -- from about every couple of days to once a week.

The early findings are based on a one-time treatment given to 16 patients.

But researchers were hopeful a larger, ongoing trial will prove the approach effective.

Hemophilia is a bleeding disorder caused by a genetic mutation. In the most common form -- hemophilia A -- people lack a properly functioning factor VIII, a protein that helps blood clot. Some people have relatively mild hemophilia -- with excessive bleeding if they sustain a cut, for example. Others have frequent spontaneous bleeding episodes into their joints and muscles.

When hemophilia is that severe, it requires regular treatment to prevent bleeding. Most often, that means infusions of lab-created factor VIII.

That factor VIII activity only lasts so long, however. So patients generally need infusions two or three times a week, explained Dr. Barbara Konkle, the lead researcher on the new trial.

Managing that regimen in daily life can be challenging, Konkle said, particularly when it's a child with hemophilia.

"Anything you can do to reduce the number of treatments will probably improve patients' quality of life," said Konkle, who is associate chief scientific officer at the nonprofit Bloodworks Northwest, in Seattle.

Her team looked at whether the new fusion protein -- dubbed BIVV001 -- can make for a longer-acting factor VIII.

The researchers recruited 16 men with severe hemophilia who were already on factor VIII treatment. (The disease primarily affects males.) Each patient was given an injection of factor VIII into a vein, followed by an injection of BIVV001.

Overall, the study found, the fusion protein extended the half-life of factor VIII by three to four times. On day 7, patients' factor VIII activity was still at a level considered high enough to prevent bleeding episodes.

It all suggests the approach could allow treatment to be weekly -- or possibly even every 10 days, said Dr. Pier Mannucci, of IRCCS Maggiore Policlinico Hospital in Milan, Italy.

To Mannucci, who wrote an editorial published with the study, the findings represent "more amazing progress" in treating hemophilia.

He pointed to key developments in recent years -- including promising findings on gene therapy, which might provide a cure to at least some people with hemophilia.

And already, patients have options other than factor VIII replacement. In 2017, the U.S. Food and Drug Administration approved a drug called emicizumab -- a lab-engineered antibody that mimics the activity of factor VIII.

Emicizumab has the advantage of being taken weekly, or even less often, and it's injected under the skin rather than into a vein, Mannucci pointed out.

But, he said, the drug lacks some benefits of an "authentic" factor VIII -- including the ability to treat sudden bleeding. So a longer-acting factor VIII could be an alternative to emicizumab, Mannucci said.

An ongoing "phase 3" trial is testing the new factor VIII product over the longer term, with patients receiving weekly doses.

Konkle said no safety issues emerged in this early study, published in the Sept. 10 New England Journal of Medicine. But the longer-term trial is needed to see whether any adverse effects, like allergic reactions, turn up.

Drugmakers Sanofi and Sobi, which are funding the research, developed BIVV001 together.

"It's really an incredible feat of bioengineering," Konkle said.

Historically, she explained, it's been difficult to create a longer-acting factor VIII. That's because the replacement protein interacts with a natural blood protein -- called von Willebrand factor -- which limits its half-life.

BIVV001, Konkle said, essentially "uncouples" the factor VIII replacement from von Willebrand factor circulating in patients' blood.

She believes the new therapy, if approved, "will be a really important addition to our treatment options."

But, Konkle added, "different approaches will be right for different patients."

No one knows what the new factor VIII therapy could cost. But on the whole, hemophilia treatments are highly expensive, according to the American Society of Hematology -- in the range of $300,000 to $500,000 a year.