Jonathan Roberts, MD: Inhibitors in hemophilia are a big deal. In hemophilia A, they happen around 30% of the time, depending on the mutation. Patients that have large gene deletions or mutations that confer essentially little or no protein being made at all have the highest rates of inhibitor development. But basically, that’s an allo-antibody that neutralizes the factor VIII. So if you give factor VIII for treatment, it’s not going to work because the inhibitor is going to neutralize the factor. There are 2 different times in life where it’s the highest rate of inhibitor development. The first is in childhood, usually up to the first 15 to 50 exposure days, but even up to 150 exposure days. So that’s just individual days the [patient has] gotten factor. There can be a risk for inhibitor development. The Medical and Scientific Advisory Council of the National Hemophilia Foundation, which I’m a member of, recommends…annual testing for all patients with hemophilia for inhibitor development. And if it does occur, then that really affects how we treat patients. So as I said, there are nonfactor therapies available that were first indicated for patients with inhibitors and have since been opened up to anyone with hemophilia being on a nonfactor treatment, but basically bypassing the inhibitor by exploiting the coagulation cascade in different ways. So for prophylaxis, that can be through an antibody. And then there are other bypassing agents activated prothrombin complex concentrates or recombinant factor VII therapy that can actually utilize the coagulation cascade to treat a bleeding event if it occurs. And then there’s the process of what we call ITII or immune tolerance induction, where we are giving the patient repetitive exposure to factor VIII. The hope is to induce tolerance so that their inhibitor goes away through repetitive exposure to the immune system. This can be successful 60% to 70% of the time, sometimes higher, sometimes lower. But it certainly requires a drastic change in the management strategy and treatment. And is more of a treatment burden from a patient perspective by far. Inhibitors can also occur in individuals with nonsevere hemophilia, which can be a challenge. I have a few patients who have been mild to moderate hemophilia patients their whole life without an inhibitor. They get an inhibitor, and then all of a sudden they’re learning how to treat themselves as if they are more severe because they are they have a severe bleeding disorder now. So if they live their entire life without developing those infusion skills, it can be a real challenge to then try to get them tolerated.

We don’t know thoroughly how to do that, but we do know that it’s important that an individual with hemophilia get some exposure to factor VIII. Now again, we’re going back to the infant question. Let’s say an infant goes on prophylaxis and they’re only exposed to a nonfactor therapy and they never see factor VIII most of the patients in the population with hemophilia have had early factor VIII exposures. So the question is are we just going to delay the potential unmasking or the presence of one of these allo-antibodies later on in life when eventually they have a surgery or something like that and they get exposed to factor or is giving a patient factor exposure early on when their immune system is developing, is that key to help prevent inhibitors? We don’t know the answers to those questions because again, universally most patients have already been exposed to factor. I think over time, as the current younger population, if they’ve never gotten factor or rarely gotten factor, we’re going to learn more. But unfortunately, there’s not really anything we can easily do to prevent inhibitors. We know how to treat bleeding if they develop. It, but to prevent it is definitely unknown.

Transcript edited for clarity.

Related Content

Hemgenix Gene Therapy Shows Long-Term Efficacy, Safety in Hemophilia B Patients

December 21st 2023

Article

Men with severe or moderately severe hemophilia B continue to display low bleeding rates and very little use of replacement therapies for at least three years following a single dose of the approved gene therapy hemgenix.

Bridging the Diversity Gap in Rare Disease Clinical Trials with Harsha Rajasimha of IndoUSrare

November 8th 2023

Podcast

Briana Contreras, an editor with Managed Healthcare Executive, spoke with Harsha Rajasimha, MD, founder and executive chairman of IndoUSrare, in this month's episode of Tuning in to the C-Suite podcast. The conversation was about how the disparity in diversity and ethnicity in rare disease clinical trials in the U.S. has led to gaps in understanding diseases and conditions, jeopardizing universal health, and increasing the economic burden of healthcare.

Listen

FDA Sets Review Date for Marstacimab to Treat Hemophilia

December 12th 2023

Article

Marstacimab is being reviewed to prevent or reduce the frequency of bleeding episodes in people with hemophilia A or B. The FDA has set an action date in the first quarter of 2024.

FDA Approves Adzynma for Rare Blood Clotting Disorder cTTP

November 27th 2023

Article

CTTP is rare hereditary blood clotting disorder stemming from a disease-causing mutation in the ADAMTS13 gene. This gene plays a crucial role in producing the ADAMTS13 enzyme, responsible for regulating blood clotting.

Study Highlights Poor Health Outcomes in Older Adults with Hemophilia

November 24th 2023

Article

People with moderate or severe hemophilia had worse joint status, lower pain thresholds, and poorer quality of life compared with people with mild hemophilia or healthy controls.

Diversity Gaps in U.S. Rare Disease Trials and the Inequalities in Hemophilia Clinical Studies

November 17th 2023

Article

Harsha Rajasimha, MD, founder and executive chairman of IndoUSrare, spoke to MHE about the current disparities in diversity and ethnicity in rare disease clinical trials in the U.S., as well as what he's seeing in clinical trials for diseases like hemophilia, in specific.