By Vicky Uhland
Before the late 1960s, when plasma-derived factor replacement therapies were developed, there were no medications for hemophilia A or B. Today, there are 28 different products. “That’s a testament to wonderful research,” said hemophilia care consultant Angela Lambing, MSN, ANP, GNP.
During the Thursday afternoon session, Basics of Gene and Innovative Therapies, a standing-room-only crowd listened and asked questions as Lambing discussed the future of genetic therapies for bleeding disorders.
Lambing said hemophilia is suitable for gene therapy because it’s caused by a single gene mutation, factor VIII and IX levels are easy to monitor, and small increases in factor levels can result in improved quality of life.
The idea behind gene therapy in hemophilia is to provide the body with a corrected gene that has instructions on how to make a factor, Lambing said. In some people, that may result in normal factor levels that don’t require infusions to prevent bleeding episodes. Others may need replacement gene therapies to reach adequate factor levels. Also, researchers don’t yet know how long factor levels can be maintained with gene therapy, she said.
Gene therapy begins with scientists developing a working copy of a gene. They then create a vector, which is essentially an empty viral shell, and put the working gene into the vector. The vector is intravenously infused into the body, where it targets the liver and gives instructions on how to produce factor.
Hemophilia gene therapy research has been around for 40 years, Lambing said. But the first trials in humans weren’t until 2011.
There are a variety of gene-transfer therapy trials underway, she said. Most of the current trials are being conducted in male adults with no comorbidities and no antibodies to the vector used in the study. Trials can last 10 years or longer.
Anti-tissue factor pathway inhibitor, or anti-TFPI, is an antibody designed to decrease TFPI, a natural protein that prevents people from clotting too much. The theory is that by reducing TFPI activity, anti-TFPI allows the generation of enough thrombin to prevent bleeding episodes.
There are currently two anti-TFPI phase 3 human trials underway, Lambing said. One is for Concizumab, which is designed to target hemophilia A and B of any severity, with or without inhibitors, in people ages 12 and older. Subcutaneous injections are given daily. The second trial is for Marstacimab, which also targets the same patients, but with weekly injections.
RNA interference therapy targeting antithrombin (RNAi) is designed to decrease the amount of antithrombin, a natural protein that prevents too much clotting.
Lambing said there’s one clinical phase 3 trial underway for an RNAi treatment called Fitusiran, which is designed for people with moderate to severe hemophilia A and B, with or without inhibitors. Fituziran is delivered subcutaneously once a month.
“Advancements in treatment options will continue for the foreseeable future, and it’s important you stay up to date,” Lambing said. “There are a lot of options out there that might be effective for you.” To learn more about current trials, go to ClinicalTrials.gov. ■