By Sandy Smith
Over the last few years, treatments for hemophilia have advanced dramatically, and more innovations are on the horizon.
“It’s an exciting time in the treatment of hemophilia, and we’ve got a lot to talk about,†said Mark T. Reding, MD, director of the Center for Bleeding and Clotting Disorders and professor of medicine at the University of Minnesota. Reding’s session, Advancements in Treatments for Hemophilia, explored seven new drugs and the potential impact of gene therapy.
“If we take a step back and look at what’s happened along the way, for the first 80 years of the 1900s, there were advances, but they weren’t the type of advances that really moved us forward,†Reding said.
Since 2014, with the development of extended half-life factors, things have begun to change.
Reding explored seven drugs currently in different phases of development that may improve the outlook for people with hemophilia A and B and, in some cases, other types of bleeding disorders.
“These seven drugs in development are all moving along very nicely, very quickly, with data starting to come out, and a lot more data anticipated in the near future,†he said. “We’re very hopeful that all of these will be approved, and we’ll have a lot more tools in our toolbox.
The first, rFVIIIFc-vWF-XTEN, may be better known by its simpler name of BIVV0001. It is expected to further extend half-life using biodegradable polymer powders. A small study of 16 individuals found the half-life was three to four times longer than factor VIII, Reding said. A Phase III study is underway and expected to be complete in January. A pediatric study began in February, and is expected to finish in 2023.
Dalcinonacog alfa (DalcA) is another promising drug in development. It can be given subcutaneously, and the volume is quite small, Reding said. It is in Phase IIB of study. “This particular factor IX is being looked at as a potential protein for gene therapy,†he said.
Mim8 is the next generation of factor VIII, and has proven to be 15 times more potent in both in vitro and animal models. “The fact that it’s potentially more potent means that this could get us closer to that normal clotting zone,†Reding said. Phase II trials won’t be complete until 2024.
MarzAA is a modified recombinant factor VIIa. “They’ve changed key parts of the protein to make it biologically work more effectively,†Reding said. Early results show a half-life of 9.5 hours and subcutaneous dosing is possible. “The more exciting thing is, they’re going to be looking beyond hemophilia into other bleeding disorders. That would be an advance as well.â€
The last three drugs—concizumab, marstacimab and fitusiran—all are non-factor replacement therapies that focus on rebalancing the coagulation system. They will be used for prophylaxis, not treatment of bleeding, Reding said. Of the three, concizumab is furthest along, with Phase III studies occurring now. One advance would be a pen delivery of a daily prophylaxis. “The company that makes this drug also makes insulin, so they have this technology.â€
Marstacimab would offer weekly subcutaneous injections, while fitusiran would be used monthly.
Gene therapy for hemophilia is another innovation on the horizon. In this method, “We fix a broken gene. If we fix that gene, we should cure the disease. The question is, ‘How do we fix the gene?’â€
Two of the most common gene therapies—CRISPR and cell therapy—are not good candidates for treatment of hemophilia, Reding said. Gene transfer therapy injects the corrected gene into the body. The vector delivers the gene to the cell. “We’re introducing functional copies of the gene back into the body. That’s the strategy for hemophilia.â€
With hemophilia A and B, there is only one gene mutation that needs to be fixed, Reding said. “That lends itself to gene therapy pretty nicely. If we can get that one protein level into place, we can have a significant impact on the disease.â€
With new drugs in the pipeline and new therapies being studied, Reding suggests everyone “strap in and hang on. There’s a lot more data coming.†â–
Join in today's session, Candid Conversations: What Do the Docs Think?, when a panel takes a close look at bleeding disorders from both the personal and medical viewpoints. Advocate Luke Pembroke moderates a discussion with three HTC physicians who will be moderating the discussion. Joining Pembroke will be Glenn Pierce, MD, PhD, independent consultant and entrepreneur-in-residence at Third Rock Ventures; Steven W. Pipe, MD, professor of pediatrics and pathology and medical director of the Pediatric Hemophilia and Coagulation Disorders Program at the University of Michigan; and Margaret V. Ragni, MD, MPH, director of the Hemophilia Center of Western Pennsylvania and professor of medicine and clinical translational science at the University of Pittsburgh. â–
