“It’s an amazing time to be a hemophilia provider,” Alice D. Ma, MD, University of North Carolina at Chapel Hill hematologist and bleeding disorder specialist, said in an interview. “There are real options, and it’s very exciting.”
But the drugs come with quirks that hematologists must understand, hemophilia specialists cautioned, and stubborn insurers pose significant obstacles to appropriate care. Also, new generations of medications in development offer both hope and more questions.
By far, the biggest game changer in hemophilia A is a monoclonal antibody called emicizumab (Hemlibra), first approved by the Food and Drug Administration for hemophilia A patients with factor VIII inhibitors and then in 2018 for those without factor VIII inhibitors.
“It’s just been getting a bigger and bigger slice of market share as patients and parents really buy in to how great that product is,” Dr. Ma said. “I do not have any hemophilia A patients with factor VIII inhibitors who aren’t on it. That’s just kind of a no-brainer, no ifs, ands, or buts.”
About 50%-60% of her noninhibitor patients with hemophilia A take the drug, she said.
According to its manufacturer, Genentech, the drug “acts like a bridge, bringing factor IXa and factor X together to allow the blood coagulation process to continue without needing to replace factor VIII.”
Since emicizumab is not a blood factor, Dr. Ma said, it doesn’t cross-react with antibodies or inhibitors. “The other thing that is pretty amazing is that it’s given subcutaneously as opposed to intravenously. It’s given under the skin, kind of like an insulin shot, rather than into a vein.”
Prophylaxis treatments did exist for patients with hemophilia A prior to emicizumab, University of North Carolina at Chapel Hill hematologist and blood disorder specialist Nigel S. Key, MB, ChB, said in an interview. But the treatments didn’t stop all bleeding. “We never really kept them under control,” he said, adding that patients needed to get infusions several times a week. “It was cumbersome and took a lot of compliance, a lot of effort to do it.
Thanks to emicizumab, adult patients don’t have to put on tourniquets and stick butterfly needles into their own veins anymore, and parents no longer need to regularly give factor infusions to their children every 2-3 days, Dr. Ma said. Instead, doses may be required just once a week.
Not every patient is eager to embrace emicizumab
Emicizumab isn’t necessarily an easy sell. Home-care company pharmacies don’t get reimbursed as much for providing emicizumab, compared with factor infusions, Dr. Ma said, and some of these companies are urging parents to not accept the drug for their kids.
Prior experience can also make people wary. According to Dr. Ma, one of her patients – a 62-year-old man – was reluctant to take factor because he’d gotten infected with HIV from an infusion. “For guys of that certain age, factor was death. It was poison, so you tried really hard not to take it.”
The patient now regrets not taking emicizumab earlier. He told Dr. Ma that his joints “do feel better than when I took factor regularly,” and “he really thinks that it has made his hemophilia recede into the background of his life, which is pretty, pretty nice.”
In fact, Dr. Ma said, he dropped a 7-pound rock on his foot but did not need to take factor or be hospitalized because of bleeding. Instead, he simply “watched a bruise form and then get better.”
As for challenges beyond convincing patients to take emicizumab, Dr. Ma said that insurers can may still refuse to pay for it in noninhibitor patients. “Some of them say you have to fail a regular clotting factor to be able to take Hemlibra,” she said, noting that she finds this viewpoint intolerable.
Hemlibra is remarkably expensive, but treatment of bleeds is also pricey. A 2021 study found that median 6-month hemostatic treatment costs in hemophilia A patients fell from more than $176,000 to barely $128,000 after they started taking the drug.
There’s another hitch. Some hematologists don’t realize that the drug can throw off certain coagulation readings. Dr. Ma recalled that a patient with hemophilia A went to a different healthcare facility for a gall bladder operation, and hematology fellows there failed to adjust his factor VIII level – an extraordinarily high 400%, suggesting high coagulation – to reflect his use of emicizumab.
“My patient bled severely and could have lost his life,” Dr. Ma said.