Rare Community Profiles

Rare Community Profiles is a new Patient Worthy article series of long-form interviews featuring various stakeholders in the rare disease community, such as patients, their families, advocates, scientists, and more.

Study Investigator Dr. Weyand Discusses the Trial Data that Led to ALTUVIIIO Approval for Hemophilia A

In March 2023, Patient Worthy shared an article discussing the U.S. Food and Drug Administration’s approval of ALTUVIIIO for individuals living with hemophilia A. ALTUVIIIO is a recombinant DNA-derived Factor VIII concentrate that is designed for prophylaxis, on-demand use, and perioperative care. Patient Worthy recently spoke with Dr. Angela Weyand, MD, one of the study investigators for the Phase 3 XTEND-1 study. This study played a key role in providing the data needed for this approval. In her discussion, Dr. Weyand describes her background, the most compelling data from the clinical trial, and the benefits that ALTUVIIIO may confer for people with hemophilia A.

PW: Please tell us about yourself and your background.

Dr. Weyand: I am a clinical associate professor at the University of Michigan Medical School and a practicing physician at C.S. Mott Children’s Hospital specializing in pediatric hematology and oncology. I attended medical school at the University of Michigan and completed my pediatrics residency at the University of Washington/Seattle Children’s Hospital before returning to the University of Michigan for my pediatric hematology and oncology fellowship. I am particularly interested in young women and girls with bleeding or clotting disorders, and am the co-director of a combined hematology/gynecology program serving this population. My research interests are in reference ranges in hematology, females with bleeding disorders, hormone provoked thrombosis, and von Willebrand disease.

In your words, what is hemophilia A?

Hemophilia A is a rare, lifelong condition in which the ability of a person’s blood to clot properly is impaired due to missing or defective factor VIII. The lack of factor VIII can cause excessive and spontaneous bleeding in patients’ joints and, over time, can lead to irreversible joint damage, pain, and life-threatening hemorrhages. The severity of hemophilia A is determined by someone’s factor activity levels. The risk of a bleed increases when those levels are lowest.

How might efanesoctocog alfa (ALTUVIIIO) improve on the current standards-of-care for hemophilia A?

Current factor VIII therapies are constrained by short half-life, leading to frequent infusion needs and variation in factor VIII levels that may be suboptimal, increasing vulnerability to bleeds. The XTEND-1 study results published in the New England Journal of Medicine demonstrated clinically meaningful prevention of bleeds and superior bleed protection compared to prior factor prophylaxis based on an intra-patient comparison.

What made you want to join the XTEND-1 study as a trial investigator? What were your responsibilities?

ALTUVIIIO is an exciting new treatment option for hemophilia A. The data from the Phase 1/2 trial was extremely compelling when I first saw it presented, so I jumped at the opportunity to advance it. As a physician, I see—every day—the toll hemophilia has on patients, especially children. They deserve better options and, hopefully, a more normal life. As trial investigator, I approached eligible patients to discuss the trial, consented interested patients, and followed them clinically throughout the course of the study.

From your vantage point, what are this study’s most meaningful findings?

The Phase 3 XTEND-1 study demonstrates that ALTUVIIIO can deliver high-sustained factor levels in the normal to near-normal range (≥40%) for the majority of the week and of 15% at day 7 with once-weekly dosing. This is exciting for patients as this can provide a lower treatment burden while also providing better protection with higher sustained factor VIII levels. Additionally, the data shows that ALTUVIIIO treatment resulted in significant and clinically meaningful improvements in physical health, pain, and joint health, showing promise for long-term quality-of-life improvement.

Will ALTUVIIIO overcome any of the barriers to care faced by people with hemophilia?

The pivotal study data continues to reinforce its potential to transform the hemophilia A treatment landscape by providing higher sustained protection for longer. Once weekly dosing will help overcome the high current burden of treatment that patients receiving factor prophylaxis must endure while also providing them with better protection against bleeds.

How was the patient voice/perspective included in the study? Why is it important to ensure that patients have a voice within medical research?

It’s important to include the patient perspective because the burden of frequent treatments can also impact the overall quality-of-life for people living with hemophilia A, such as mental health, and may lead to anxiety or depression. This was kept in mind when the trial was designed.

I’m especially proud that XTEND-1 included a female patient. Starting in medical school, doctors are taught that hemophilia is a male disease. But that really isn’t the case. We are now realizing that far more women suffer from hemophilia than we previously thought. We know that, based on epidemiology, a higher number of women are affected than what we are currently capturing in our registries. This is likely because they are not being diagnosed and are thus underrepresented. There’s a lot of work to be done to ensure women with hemophilia receive equitable care and the inclusion of female patients in clinical studies is an important step towards that.

Medical research is always evolving to better serve patients. Exit interviews were conducted in a subgroup of patients to better understand the clinical meaningfulness of the patient-reported endpoints for physical health and pain and supported the improvements in physical health with ALTUVIIIO.

Ultimately, unmet needs remain for people with hemophilia to strengthen protection, reduce treatment burden, and improve quality-of-life to live beyond the limits of their disease. For years, the hemophilia community has been hoping for a truly extended half-life factor VIII product to improve patient lives—and with ALTUVIIIO, it is finally here.