The Future's So... BRIGHT

The Future's So... BRIGHT

Published: LifeLines for Health, vol. 12 (Fall/Winter 2018)

by: Janet Brewer, M.Ed


The bleeding disorders community is currently experiencing one of the most rapid growth periods since the 1990’s when recombinant products hit the market. Corporate buyouts bring changing companies, some of whom are completely new players to the bleeding disorder community. New products that provide the convenience of subcutaneous administration are here, with more coming, gene therapy for FIX may be just around the corner, with FVIII not far behind. Women’s bleeding symptoms are finally being recognized. It is truly a dizzying pace and we do this for a living! With each of these advances however, the benefit-risk profile for any and all new products and treatments must be first and foremost in our minds. 

So, what is going on? 

Gene Therapy 

A cure in our lifetime was the refrain when my brother was born in 1970. Multiple attempts at gene therapy have occurred in the last 4 decades, but it is clearly looking to become a treatment option in the next five years, especially for Hemophilia B. Companies such as Spark and BioMarin are on the leading edge. 

No one is saying yet that hemophilia will be cured. Currently, gene therapy — which uses a virus to deliver a new gene to cells — can only be used once. If it stops working, the patients lose the benefits. For now, “we are anticipating that this is a once-in-a-lifetime treatment,” said Dr. Steven Pipe, director of the hemophilia and coagulation disorders program at the University of Michigan and a lead investigator of a clinical trial conducted by the biotech company BioMarin (https://www.nytimes. com/2018/08/13/health/hemophilia-gene-therapy.html) 

Many questions exist however, regarding its long term-safety and efficacy. The FDA has a draft document that’s currently open for comments, entitled Human Gene Therapy for Hemophilia at: BiologicsBloodVaccines/ GuidanceComplianceRegulatoryInformation/ Guidances/CellularandGeneTherapy/ 


The document covers considerations for product development, consideration for FVIII/FIX activity measurement assessed by different clinical laboratory assays, expedited programs, communication with the FDA, considerations for preclinical studies, and considerations for clinical trials to include:

Efficacy Endpoints

Study Population

Study Monitoring

Study Design

Statistical Considerations

Patient Experience

Increased patient monitoring efforts that are well-established and enforced with clear cut guidelines for what constitutes an adverse event with proper reporting procedures, should be part of the approval process. Our community has a well-documented history of what can go wrong when products that are considered “life changing” are introduced into our treatment regiments.


For many in the inhibitor community, Hemlibra has proven to be a game-changer in care. There is no doubt it has decreased bleeding and consequently increased quality of life for inhibitor patients where nothing else has worked. The convenience of subcutaneous treatment after years of port therapy and complications has led to unprecedented recommendations for its use.

Genentech announced the release of Hemlibra to hemophilia A patients without an inhibitor on October 4, 2018. This comes less than a year after its approval on November 18, 2017 for the treatment of hemophilia A patients with an inhibitor.

During Dr. Stacy Croteau (Boston Children’s Hospital) and Dr. Lindsey George’s presentation, Update on New Therapies and Gene Therapy Trials in Hemophilia for physicians at NHF, October 18th-21st, 2018, they explained, emicizumab/Hemlibra is a hot topic. The HAVEN 3 noninhibitor patient study also shows that “emi” (emicizumab) is better than treating on demand. However, there were adverse events occurring in at least 5 percent of participants including injection site reaction, headache and diarrhea. Dr. Croteau also concludes that there is “significant laboratory monitoring challenges and (a) lack of understanding of effective hemostasis provided by emi alone and that more information is needed concerning those who have had major trauma or surgery.”

Dr. Glen Pierce concludes that, “questions remain; while it mimics FVIII in bringing FIX and X together, it doesn’t simulate other functions of FVIII.”

The American Thrombosis and Hemostasis Network (ATHN) announced the launch of ATHN7: Hemophilia Natural History Study Overview at NHF this October. The study’s intent is to follow a group of people over time to collect health information from patients to understand how bleeding and clotting disorders like hemophilia develop and to design effective treatments. According to Dr. Tyler Buckner, one of the lead researchers at Hemophilia and Thrombosis Center, University of Colorado, “ATHN 7 is looking to find out whether non-factor replacement products are safe when used as a preventative measure for patients who have inhibitors as well as for those who don’t. We’re also going to be evaluating the effectiveness of non-factor products*, bypassing agents, or coagulation factor replacement products when used for prevention and for surgery in patients with hemophilia.” - NHF Daily 

Want to participate? Hemophilia A or B patients of any severity with or without an inhibitor are eligible through their hemophilia treatment center over a multiple year period. *For the purposes of this study, “non-factor products are those that became commercially available in the US after January 1, 2017.”

My Life Our Future

Until the end of 2017, My Life Our Future (MLOF), originally supported by ATHN, Biogen, Bloodworks Northwest and NHF gathered genotypic data from 9,000+ hemophilia A and B patients and carriers. Your support of this invaluable data collection contributed to the MLOF Research Repository, the largest hemophilia scientific resource of its kind in the world. Over 4,000 genetic variations in hemophilia were discovered as a result of this research, which will hopefully answer questions such as, which variants increase the risk of inhibitor formation, or why bleeding severity varies from person to person? Some of the research projects that will be explored using this repository include: Inhibitor Development, Bleeding Specific to Hemophilia A and Hemophilia B, FVIII clearance, and Carriers.


Doctors Hong Yang and Zuben Suana of the FDA’s Center for Biologics Evaluation and Research (CBER) will utilize MLOF data to create a mathematical model to predict the body’s immune response to treatment. Once validated, it could be used to evaluate new FVIII drugs, project the risk of the development of antibodies, and help determine appropriate treatment for newly diagnosed patients. Eventually, it may also help inform development of specific treatments for people with different types of hemophilia A. - NHF Daily October 13, 2018

Want to know more about MLOF? Visit

It is truly an exciting time in the bleeding disorders community! Since 2017, CHES has had the great fortune to collaborate with Dr. Diane Nugent, CHOC and her team from The Center for Inherited Blood Disorders in Orange, California and Hematology Advanced Diagnostic Lab (HADL) to offer whole gene molecular sequencing for our FVII patients at the Factor 7 Retreat initiated in 2012. The overarching goal was to provide molecular diagnosis and variant identification for patients and family members with FVII deficiency to ascertain why bleeding symptoms and severity levels do not correspond. The discoveries made as a result of this project have led to abstract presentations at both World Federation of Hemophilia (WFH) and International Society of Thrombosis and Hemophilia (ISTH) 2018. This preliminary research clearly indicates that the factor VII levels do not correlate with the bleeding phenotype and that there are mutations that are more closely associated with increased bleeding, regardless of factor level. 

So, what does this have to do with hemophilia and inhibitors you may ask? There is still so much we do not know in the world of bleeding disorders and many think we are just scratching the tip of the iceberg. We are caught up in a wave of new science, new studies, new products which are all very exciting! New advancements also create multiple unknowns. In this time of significant change, continue to do your research, reflect on our community’s history, ask questions and don’t hesitate to speak up if a decision just doesn’t feel right for you. The choice to use any product or protocol is yours, alone. After all, it is your own or your child’s body you are making decisions about and those choices can have benefits or consequences for a lifetime.