Global Hemophilia Report

This season opener explores comprehensive hemophilia care in 2025: what's working, what's strained, and what needs to evolve. Clinicians from the US, UK, and Ireland join host Patrick James Lynch and Dr. Donna DiMichele to discuss treatment personalization, shared decision-making, psychosocial burden, and global sustainability challenges. Guest Megan Iditarod from Nigeria offers perspective on delivering comprehensive care with limited resources, highlighting the universal need for multidisciplinary support and good data collection.   Guests: Megan Iditarod Kate Khair, PhD Amy Dunn, MD Prof Niamh O'Connell, MB PhD   Senior Advisor: Donna DiMichele, MD   Hosted by: Patrick James Lynch   Featured Advertiser: Sanofi   Subscribe to the Global Hemophilia Report   Show Notes:   #MyHemophiliaTruth. Real stories. Powered by Sanofi. It's time to consider the whole experience when it comes to managing hemophilia and change the conversation. Explore the full story at www.myhemophiliatruth.com   Connect with the Global Hemophilia Report Global Hemophilia Report on LinkedIn Global Hemophilia Report on X/Twitter Global Hemophilia Report on Facebook   Connect with BloodStream Media: BloodStreamMedia.com BloodStream on Facebook  BloodStream on X/Twitter   

In this special episode, host Patrick James Lynch reflects on turning forty…and on forty years of life with hemophilia. Joined by Dr. Donna DiMichele, Patrick traces the parallel evolution of his own experience and the hemophilia community's journey through crisis, discovery, and innovation. From the HIV epidemic of the 1980s to the arrival of gene therapy and digital health, they explore how science, data, and humanity have shaped the story of hemophilia. Together, they ask: what have we learned, what still can't be measured, and what might the next forty years hold? Guests: Donna DiMichele, MD   Senior Advisor: Donna DiMichele, MD   Hosted by: Patrick James Lynch   Featured Advertiser: Sanofi   Subscribe to the Global Hemophilia Report   Show Notes:   Join Kevin as he shares about his journey with hemophilia and the hurdles he faced in communicating with friends, family, and healthcare providers about his condition. He highlights how hemophilia affects far more than just physical health — and why honest, open conversations that focus on the full patient experience, not just symptoms, are so essential.   Click here to watch his story: https://www.youtube.com/watch?v=3v1cCTbhClA&list=PLmqBxf22n4lNK82h3QZ-9YlpIjYdzDOer&index=5   Rich's Story Join Rich as he discusses how hemophilia has impacted his ability to travel and live an active lifestyle. He highlights how hemophilia affects far more than just physical health and shares his journey of overcoming barriers to be able to safely travel internationally, fly fish, garden, and more.    Click here to watch his story: https://www.youtube.com/watch?v=ihEvFywE43E&list=PLmqBxf22n4lNK82h3QZ-9YlpIjYdzDOer&index=8   Connect with the Global Hemophilia Report Global Hemophilia Report on LinkedIn Global Hemophilia Report on X/Twitter Global Hemophilia Report on Facebook   Connect with BloodStream Media: BloodStreamMedia.com BloodStream on Facebook  BloodStream on X/Twitter   

In this episode, we take a deep dive into the state of the treatment pipeline for bleeding disorders. From the way clinical trials are structured to what's actually available for different conditions, we examine both the promise and the reality of innovation in this space. Recorded live at the NBDF Bleeding Disorders Conference, we join Mike Recht, MD, PhD, Chief Science and Medical Officer of NBDF, for a "research posters walk & talk" to explore what's happening right now — and why so many promising treatments never make it to market. Guests: Mike Recht, MD, PhD Maria Santaella, PhD(c), MSN, RN-BC, CPHON Samantha Carlson, LMSW   Senior Advisor: Donna DiMichele, MD   Hosted by: Patrick James Lynch   Written by: Kay Vermeil   Featured Advertiser: Sanofi   Subscribe to the Global Hemophilia Report   Show Notes:   Join Kevin as he shares about his journey with hemophilia and the hurdles he faced in communicating with friends, family, and healthcare providers about his condition. He highlights how hemophilia affects far more than just physical health — and why honest, open conversations that focus on the full patient experience, not just symptoms, are so essential.   Click here to watch his story: https://www.youtube.com/watch?v=3v1cCTbhClA&list=PLmqBxf22n4lNK82h3QZ-9YlpIjYdzDOer&index=5   Sanofi's Global Hemophilia Survey uncovers significant care gaps and emotional challenges faced by patients and caregivers. Learn how improving health literacy and fostering better patient-provider communication are essential to addressing these inequities. Explore the findings and see how Sanofi is driving health equity for the hemophilia community. Explore the survey findings here: Global Hemophilia Survey Page. Connect with the Global Hemophilia Report Global Hemophilia Report on LinkedIn Global Hemophilia Report on X/Twitter Global Hemophilia Report on Facebook   Connect with BloodStream Media: BloodStreamMedia.com BloodStream on Facebook  BloodStream on X/Twitter   

This episode of the Global Hemophilia Report explores the long-overdue conversation about women with hemophilia. Experts discuss the challenges women face in getting diagnosed, the persistent gaps in clinical research and care, and the impact of outdated language and systemic bias. The panel highlights the need for better data, more inclusive clinical trials, and a shift in medical culture to ensure women with hemophilia are recognized and prioritized.    Guests: Andra James, MD, MPH Michelle Sholzberg MDCM, FRCPC, MSc. Dawn Rotellini Len Valentino, MD Robert Sidonio, Jr., MD   Senior Advisor: Donna DiMichele, MD   Hosted by: Patrick James Lynch   Written by: Kay Vermeil   Featured Advertiser: Sanofi   Subscribe to the Global Hemophilia Report   Show Notes:   Presenting Sponsor: Presented by Sanofi Join Shellye as she shares her inspiring journey as a woman living with hemophilia. After years of unanswered questions, her diagnosis highlights the critical role of health literacy in bridging care gaps. Through advocacy, Shellye raises awareness and empowers underserved communities. Watch her story and see how health literacy can break barriers and transform lives. Click here to watch her story: Sanofi – See Hemophilia Through My Eyes: Women & Girls For too long, women and girls who bleed have been dismissed. Left out of the narrative. Ignored by the system. But not anymore. In our new film, "Dismissed," meet Isabelle—a 15-year-old with hemophilia who's using her voice to uplift the unheard. Alongside her are four powerful stories of women challenging what's "normal" and demanding recognition, care, and justice. This is more than a film. It's a movement. 📽️ Watch and share the trailer now. Learn more at http://dismissedfilm.com/   Connect with the Global Hemophilia Report Global Hemophilia Report on LinkedIn Global Hemophilia Report on X/Twitter Global Hemophilia Report on Facebook   Connect with BloodStream Media: BloodStreamMedia.com BloodStream on Facebook  BloodStream on X/Twitter  

In this episode of the Global Hemophilia Report, host Patrick James Lynch and a panel of experts discuss the importance of real world data and patient engagement in hemophilia care. The conversation explores how data collected outside of clinical trials provides deeper insights into treatment outcomes, challenges, and lived experiences. Guests share strategies for improving data reliability, motivating patient participation, and balancing privacy with research needs. Tune in for key takeaways on how both numbers and personal stories shape better care for the hemophilia community.   Guests: Mike Recht, MD, PhD, MBA Samantha Gouw, MD, PhD Maria Santaella, RN-BC, MSN, PhD(c)   Senior Advisor: Donna DiMichele, MD   Hosted by: Patrick James Lynch   Written by: Kay Vermeil   Featured Advertiser: Sanofi   Subscribe to the Global Hemophilia Report   Show Notes:   Presenting Sponsor: Presented by Sanofi   Sanofi's Global Hemophilia Survey uncovers significant care gaps and emotional challenges faced by patients and caregivers. Learn how improving health literacy and fostering better patient-provider communication are essential to addressing these inequities. Explore the findings and see how Sanofi is driving health equity for the hemophilia community. Explore the survey findings here: Global Hemophilia Survey Page. For too long, women and girls who bleed have been dismissed. Left out of the narrative. Ignored by the system. But not anymore. In our new film, "Dismissed," meet Isabelle—a 15-year-old with hemophilia who's using her voice to uplift the unheard. Alongside her are four powerful stories of women challenging what's "normal" and demanding recognition, care, and justice. This is more than a film. It's a movement. 📽️ Watch and share the trailer now. Learn more at http://dismissedfilm.com/   Connect with the Global Hemophilia Report Global Hemophilia Report on LinkedIn Global Hemophilia Report on X/Twitter Global Hemophilia Report on Facebook   Connect with BloodStream Media: BloodStreamMedia.com BloodStream on Facebook  BloodStream on X/Twitter   

On this episode, we explore the concept of shared decision making (SDM) in modern hemophilia care. With insights from experts Brendan Hayes and Dr. Cedric Hermans, the discussion explores the evolution of treatment options, patient education, and the collaborative decision-making process. The conversation also highlights the development and impact of the SDM tool by the World Federation of Hemophilia, emphasizing the importance of patient empowerment and ongoing education.   Guests: Kate Bazinsky Randy Curtis Debbie de la Riva Jackie Bottacari   Senior Advisor: Donna DiMichele, MD   Hosted & Written by: Patrick James Lynch   Featured Advertiser: Sanofi   Subscribe to the Global Hemophilia Report   Show Notes:   #MyHemophiliaTruth. Real stories. Powered by Sanofi. It's time to consider the whole experience when it comes to managing hemophilia and change the conversation. Explore the full story at www.myhemophiliatruth.com   Emil's Story: Join Emil as he opens up about his journey living with hemophilia and the profound impact it has had on his mental health. He emphasizes how the effects of hemophilia extend beyond physical symptoms and underscores the importance of recognizing its emotional and psychological challenges. Emil also highlights the need for comprehensive care that supports both the mental and physical health of children and adults living with hemophilia.   Click here to watch his story: https://www.youtube.com/watch?v=9ljWxS57-ZA&list=PLmqBxf22n4lPMpAfLe4yv8haC6Ejcp1XL&index=2   Connect with the Global Hemophilia Report Global Hemophilia Report on LinkedIn Global Hemophilia Report on X/Twitter Global Hemophilia Report on Facebook   Connect with BloodStream Media: BloodStreamMedia.com BloodStream on Facebook  BloodStream on X/Twitter

On this episode, we delve into the concept of shared decision making (SDM) in modern hemophilia care. With insights from experts Brendan Hayes and Dr. Cedric Hermans, the discussion explores the evolution of treatment options, patient education, and the collaborative decision-making process. The conversation also highlights the development and impact of the SDM tool by the World Federation of Hemophilia, emphasizing the importance of patient empowerment and ongoing education.   Guests: Brendan Hayes, MPH, CPH Cedric Hermans MD PhD FRCP   Senior Advisor: Donna DiMichele, MD   Hosted & Written by: Patrick James Lynch   Featured Advertiser: Sanofi   Subscribe to the Global Hemophilia Report   Show Notes:   #MyHemophiliaTruth. Real stories. Powered by Sanofi. It's time to consider the whole experience when it comes to managing hemophilia and change the conversation. Explore the full story at www.myhemophiliatruth.com   Mark's Story Join Mark as he shares about his experience living with hemophilia, including the impact it had on building and maintaining relationships throughout grade school, college, dating, and raising his family. Mark also highlights how shared decision making with his healthcare providers, and strong family and caregiver support in those decisions, can make all the difference when it comes to managing the daily challenges of hemophilia.   Click here to watch his story: https://www.youtube.com/watch?v=tQ8oeM0zL24&list=PLmqBxf22n4lPMpAfLe4yv8haC6Ejcp1XL&index=8   Connect with the Global Hemophilia Report Global Hemophilia Report on LinkedIn Global Hemophilia Report on X/Twitter Global Hemophilia Report on Facebook   Connect with BloodStream Media: BloodStreamMedia.com BloodStream on Facebook  BloodStream on X/Twitter   

On this episode of the Global Hemophilia Report, we discuss the limitations of current hemophilia care metrics. They explore the importance of measuring the impact on quality of life, the role of nurse-patient relationships, and the challenges faced by underrepresented patient groups, such as those with moderate hemophilia and women.    Guests: Brittany Savage, NP Cathy Harrison, RN, Adv Dip, BMedSci, MSc   Senior Advisor: Donna DiMichele, MD   Hosted & Written by: Patrick James Lynch   Featured Advertiser: Sanofi   Subscribe to the Global Hemophilia Report   Show Notes:   #MyHemophiliaTruth. Real stories. Powered by Sanofi. It's time to consider the whole experience when it comes to managing hemophilia and change the conversation. Explore the full story at www.myhemophiliatruth.com   The Bigger Picture in Hemophilia B:  Hemophilia A and hemophilia B are different bleeding disorders with unique pathologies and clinical features.1 Due to the distinct behavior of factor IX, multiple PK parameters should be considered when assessing bleed prevention. Learn how a broader view of PK may influence evaluation of treatment and management for patients with hemophilia B.2,3 Learn more at thebiggerpictureinhemb.com  1. Castaman G, Matino D. Haematologica. 2019;104(9):1702-1709. 2. Dolan G, Benson G, Duffy A, et al. Blood Rev. 2018;32(1):52-60.  3. Mann DM, Stafford KA, Poon M-C, Matino D, Stafford DW. Haemophilia. 2021;27(3):332-339. Connect with the Global Hemophilia Report Global Hemophilia Report on LinkedIn Global Hemophilia Report on Twitter Global Hemophilia Report on Facebook   Connect with BloodStream Media: BloodStreamMedia.com BloodStream on Facebook  BloodStream on Twitter   

On this episode of the Global Hemophilia Report, we explore the critical topic of health literacy and its direct impact on health equity within the bleeding disorders community. Featuring insights from experts, the discussion highlights the urgent need to address gaps in health literacy to ensure better medical outcomes. The episode also examines the challenges posed by recent rollbacks of diversity, equity, and inclusion policies and presents innovative solutions being utilized to bridge these gaps.   Guests: Kerry Funkhouser, EdD Brendan Hayes, MPH, CPH Paula James, MD Magdalena Lewandowska, MD, CACP Keri Norris, PhD, JM, MPH, MCHES   Senior Advisor: Donna DiMichele, MD   Hosted & Written by: Patrick James Lynch   Featured Advertiser: Sanofi   Subscribe to the Global Hemophilia Report   Show Notes: Join Shellye as she shares her inspiring journey as a woman living with hemophilia. After years of unanswered questions, her diagnosis highlights the critical role of health literacy in bridging care gaps. Through advocacy, Shellye raises awareness and empowers underserved communities. Watch her story and see how health literacy can break barriers and transform lives. Click here to watch her story: Sanofi – See Hemophilia Through My Eyes: Women & Girls   Sanofi's Global Hemophilia Survey uncovers significant care gaps and emotional challenges faced by patients and caregivers. Learn how improving health literacy and fostering better patient-provider communication are essential to addressing these inequities. Explore the findings and see how Sanofi is driving health equity for the hemophilia community. Explore the survey findings here: Global Hemophilia Survey Page.   Connect with the Global Hemophilia Report Global Hemophilia Report on LinkedIn Global Hemophilia Report on Twitter Global Hemophilia Report on Facebook   Connect with BloodStream Media: BloodStreamMedia.com BloodStream on Facebook  BloodStream on Twitter   

On this episode of the Global Hemophilia Report, we speak with guests who are each pioneering hemophilia advocacy in their respective regions. The discussion highlights the pivotal role of data and patient storytelling in driving systemic change and policy advancements. The episode emphasizes how global collaboration and technological innovations are paving the way for more equitable hemophilia care worldwide.    Guests: Harshal Kale, World Federation of Hemophilia Matthew Delaney, National Bleeding Disorders Foundation Megan Adediran, Hemophilia of Nigeria   Senior Advisor: Donna DiMichele, MD   Hosted & Written by: Patrick James Lynch   Featured Advertiser: Sanofi   Subscribe to the Global Hemophilia Report   Show Notes: Connect with the Global Hemophilia Report Global Hemophilia Report on LinkedIn Global Hemophilia Report on Twitter Global Hemophilia Report on Facebook   Connect with BloodStream Media: BloodStreamMedia.com BloodStream on Facebook  BloodStream on Twitter   

On this episode of the Global Hemophilia Report, host Patrick James Lynch and Senior Advisor Dr. Donna DiMichele review significant discussions from the season on therapeutic advancements, patient advocacy, and critical hematological research. They highlight key topics explored, such as the evolving therapeutic landscape, the role of data and patient involvement in advancing hemophilia care, and the persisting challenges in treatment, particularly for hemophilia B patients. The episode also addresses the impact of artificial intelligence in research and the importance of securing funding for post-licensure studies.   Senior Advisor: Donna DiMichele, MD   Hosted & Written by: Patrick James Lynch   Featured Advertiser: Sanofi   Subscribe to the Global Hemophilia Report   Show Notes: Connect with the Global Hemophilia Report Global Hemophilia Report on LinkedIn Global Hemophilia Report on Twitter Global Hemophilia Report on Facebook   Connect with BloodStream Media: BloodStreamMedia.com BloodStream on Facebook  BloodStream on Twitter   

The comprehensive care model for hemophiliathe is experiencing transformative evolution. Our panel of esteemed experts highlight how data and innovation are driving change across the globe, and share their insights on the challenges and advancements in advancing specialized care for individuals with hemophilia.   Contributors: Amy Dunn, M.D. Sanjay Ahuja, M.D.  Cedric Hermans, M.D.,  Ph.D., FRCP Jan Blatný, M.D., Ph.D Suely Rezende, M.D., Ph.D   Senior Advisor: Donna DiMichele, MD   Hosted & Written by: Patrick James Lynch   Featured Advertiser: Sanofi   Subscribe to the Global Hemophilia Report   Show Notes: Connect with the Global Hemophilia Report Global Hemophilia Report on LinkedIn Global Hemophilia Report on Twitter Global Hemophilia Report on Facebook   Connect with BloodStream Media: BloodStreamMedia.com BloodStream on Facebook  BloodStream on Twitter

This episode of the Global Hemophilia Report podcast explores the significance of grassroots advocacy within hemophilia associations and chapters, emphasizing the critical role of data in advancing advocacy efforts. Experts from various U.S. organizations discuss the historical impact of the 1980s blood contamination crisis and the evolution of advocacy through its challenges and triumphs. The conversation highlights the importance of data collection, transparency, and community engagement in sustaining and enhancing treatment and support for those affected by hemophilia. The episode also addresses future advocacy strategies and the importance of continuous collaboration at the national and local levels. Contributors: Rigo Garcia, Hemophilia Federation of Southern California Sue Lerch, Great Lakes VE HTC Sue Martin, Bleeding Disorders Association of South Carolina Linda Mugford, Hemophilia Association of New York, Inc. Ray Stanhope, Lone Star Bleeding Disorders Foundation Senior Advisor: Donna DiMichele, MD   Hosted & Written by: Patrick James Lynch   Featured Advertiser: Sanofi   Subscribe to the Global Hemophilia Report   Show Notes: Connect with the Global Hemophilia Report Global Hemophilia Report on LinkedIn Global Hemophilia Report on Twitter Global Hemophilia Report on Facebook   Connect with BloodStream Media: BloodStreamMedia.com BloodStream on Facebook  BloodStream on Twitter   

On this episode we talk with experts Dr. Amy Shapiro, Dr. Maria Elisa Mancuso, Dr. Steve Pipe, Dr. Johnny Mahlangu, and Dr. Lynn Malec to delve into the ongoing evolution of hemophilia therapies. The discussion highlights recent advancements in treatments such as emicizumab, extended half-life factor VIII therapies, and investigates medications in clinical trials like Concizumab, Marstacimab, and Fitusiran. The episode also reflects on the role of treatment individualization and the need for more inclusive research data.   Contributors: Johnny Mahlangu, MBBCh, MMed, FCPath Lynn Malec, MD, MSc Elisa Mancuso, MD Steven Pipe, MD Amy Shapiro, MD   Senior Advisor: Donna DiMichele, MD   Hosted & Written by: Patrick James Lynch   Featured Advertiser: Sanofi   Subscribe to the Global Hemophilia Report   Show Notes: Connect with the Global Hemophilia Report Global Hemophilia Report on LinkedIn Global Hemophilia Report on Twitter Global Hemophilia Report on Facebook   Connect with BloodStream Media: BloodStreamMedia.com BloodStream on Facebook  BloodStream on Twitter   

On this episode of the Global Hemophilia Report, Senior Advisor Dr. Donna DiMichele leads a comprehensive discussion on FVIII inhibitors—a critical complication in Hemophilia A. The episode features experts such as Dr. Kathleen Pratt, Dr. David Lillicrap, Dr. Bhavya Doshi, Dr. Carol Miao, and Dr. Radek Kazmarek who explore the intricacies of immune responses, gene therapy, and novel therapies like emicizumab. They delve into factors like antigen-presenting cells, B cells, T cells, microbiome effects, and glycans that influence inhibitor development and tolerance. Despite advancements in treatment, the experts underscore the enduring importance of ongoing research in understanding and preventing FVIII inhibitors.   Contributors: Glaivy Batsuli, MD Bhavya Doshi, MD David Lillicrap, MD Carol Miao, PhD Kathleen Pratt, PhD Radek Kaczmarek, PhD   Senior Advisor: Donna DiMichele, MD   Hosted & Written by: Patrick James Lynch   Featured Advertiser: Sanofi   Subscribe to the Global Hemophilia Report   Show Notes: Listen to the Global Hemophilia Report Episode 1: Inhibitors: Prevention, Eradication, and Lived Experiences   Conflicts of Interest: Dr. Kathleen Pratt is an inventor on patents related to factor VIII immunogenicity, and she has received research funding in the past from pharmaceutical companies that manufacture human FVIII. She has no other relevant conflicts to report.   Disclaimer: The contents of Dr. Pratt's presentation are the sole responsibility of the speaker and do not necessarily reflect the views, opinions or policies of Uniformed Services University of the Health Sciences (USUHS), The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., the Department of Defense (DoD) or the Departments of the Army, Navy, or Air Force. Mention of trade names, commercial products, or organizations does not imply endorsement by the U.S. Government.    Connect with the Global Hemophilia Report Global Hemophilia Report on LinkedIn Global Hemophilia Report on Twitter Global Hemophilia Report on Facebook   Connect with BloodStream Media: BloodStreamMedia.com BloodStream on Facebook  BloodStream on Twitter  

In this episode of the Global Hemophilia Report, we delve into the crucial role of Lived Experience Experts (LEEs) in hemophilia research. Featuring a distinguished panel, the discussion covers the evolution, importance, and future of LEE involvement in research. The episode emphasizes the pivotal contributions of LEEs in making research more relevant and impactful, driven by personal and community experiences.   Contributors: Len Valentino MD Samantha Carlson MSW, LMSW Randy Curtis Ray Stanhope Kyle Davis MD   Senior Advisor: Donna DiMichele, MD   Special Episode Advisor: Maria Santaella PhD(c), MSN, RN-BC, CPHON   Hosted & Written by: Patrick James Lynch   Featured Advertiser: Sanofi   Subscribe to the Global Hemophilia Report   Show Notes: Presenting Sponsor: Sanofi   Subscribe to the Global Hemophilia Report   Connect with the Global Hemophilia Report Global Hemophilia Report on LinkedIn Global Hemophilia Report on Twitter Global Hemophilia Report on Facebook   Connect with BloodStream Media: BloodStreamMedia.com BloodStream on Facebook  BloodStream on Twitter   

Our panel of subject matter and lived experience experts engage in a data-driven discussion about caregiver burden in hemophilia, historically, and how the rapidly evolving treatment landscapes impacts that burden. Contributors: Michelle Witkop, DNP, FNP-BC Kate Khair, PhD Beatriz Caceres, MD Kasha Lumsden, BSN, RN, RAC-CT Yasmin Pavri    Senior Advisor: Donna DiMichele, MD   Special Episode Advisor: Michelle Witkop, DNP, FNP-BC   Hosted & Written by: Patrick James Lynch   Featured Advertiser: Sanofi   Subscribe to the Global Hemophilia Report   Show Notes: Presenting Sponsor: Sanofi   Subscribe to the Global Hemophilia Report   Connect with the Global Hemophilia Report Global Hemophilia Report on LinkedIn Global Hemophilia Report on Twitter Global Hemophilia Report on Facebook   Connect with BloodStream Media: BloodStreamMedia.com BloodStream on Facebook  BloodStream on Twitter   

On this episode of the Global Hemophilia Report, host Patrick James Lynch is on location in Madrid, Spain for the WFH 2024 World Congress. Patrick talks about the history of World Hemophilia Day and talks with some of the attendees at the congress. Contributors: Hazri Aris Johnny Mahlangu Rebecca, Hematology Resident   Senior Advisor: Donna DiMichele, MD   Hosted & Written by: Patrick James Lynch Featured Advertiser: Sanofi   Subscribe to the Global Hemophilia Report Show Notes: Presenting Sponsor: Sanofi   Subscribe to the Global Hemophilia Report   Connect with the Global Hemophilia Report Global Hemophilia Report on LinkedIn Global Hemophilia Report on Twitter Global Hemophilia Report on Facebook   Connect with BloodStream Media: BloodStreamMedia.com BloodStream on Facebook  BloodStream on Twitter

The topic of discussion for this episode leans more toward the scientific side but has huge clinical relevance. For today, we will be asking our expert panel to lend their experience and expertise to the topic of FVIII and FIX, which we will be discussing from several related perspectives.    Contributors: Radek Kaczmarek, PhD, MSc; University of Indiana, USA Peter Lenting, PhD; INSERM, Paris, France Ben Samuelson -Jones, M.D., PhD; CHOP Research Institute, USA Courtney Thornburg, M.D., MS; Rady Children's Hospital, UCSD, USA   Senior Advisor: Donna DiMichele, MD   Hosted & Written by: Patrick James Lynch   Featured Advertiser: Sanofi   Subscribe to the Global Hemophilia Report   Show Notes: Presenting Sponsor: Sanofi   Subscribe to the Global Hemophilia Report   Connect with the Global Hemophilia Report Global Hemophilia Report on LinkedIn Global Hemophilia Report on Twitter Global Hemophilia Report on Facebook   Connect with BloodStream Media: BloodStreamMedia.com BloodStream on Facebook  BloodStream on Twitter

Gene therapy for hemophilia A and B now exists as a licensed, prescribable treatment option for patients in certain countries; however, many questions and challenges remain. Senior advisor Dr. Donna DiMichele and patient-host Patrick James Lynch speak to global KOLs about the current state of hemophilia A and B gene therapies, both commercially and investigationally.   Contributors: Lindsey A. George, MD Margareth Ozelo, MD Steven Pipe, MD   Senior Advisor: Donna DiMichele, MD   Hosted & Written by: Patrick James Lynch   Featured Advertiser: Sanofi   Subscribe to the Global Hemophilia Report   Notes and References:   Nathwani: Hematology Am Soc Hematol Educ Program . 2022 Dec 9;2022(1):569-578.   The current state of this exciting and rapidly evolving field, as well as the challenges that need to be overcome for the widespread adaptation of this new treatment paradigm, is the subject of this review.   Pipe: N Engl J Med. 2023 Feb 23;388(8):706-718   The annualized bleeding rate decreased from 4.19 (95% confidence interval [CI], 3.22 to 5.45) during the lead-in period to 1.51 (95% CI, 0.81 to 2.82) during months 7 through 18 after treatment, for a rate ratio of 0.36 (95% Wald CI, 0.20 to 0.64; P<0.001), demonstrating noninferiority and superiority of etranacogene dezaparvovec as compared with factor IX prophylaxis. Factor IX activity had increased from baseline by a least-squares mean of 36.2 percentage points (95% CI, 31.4 to 41.0) at 6 months and 34.3 percentage points (95% CI, 29.5 to 39.1) at 18 months after treatment, and usage of factor IX concentrate decreased by a mean of 248,825 IU per year per participant in the post-treatment period (P<0.001 for all three comparisons). Benefits and safety were observed in participants with predose AAV5 neutralizing antibody titers of less than 700. No treatment-related serious adverse events occurred.   Long-Term Effects of Hemophilia B Gene Therapy. Makris M.N Engl J Med. 2023 May 18;388(20):1918.    Long-Term Effects of Hemophilia B Gene Therapy. Reply. Pipe SW, Monahan PE.N Engl J Med. 2023 May 18;388(20):1918-1919   Mahlangu: N Engl J Med. 2023 Feb 23;388(8):694-705   Results: At week 104, a total of 132 participants, including 112 with data that were prospectively collected at baseline, remained in the study. The mean annualized treated bleeding rate decreased by 84.5% from baseline (P<0.001) among the participants. From week 76 onward, the trajectory of the transgene-derived factor VIII activity showed first-order elimination kinetics; the model-estimated typical half-life of the transgene-derived factor VIII production system was 123 weeks (95% confidence interval, 84 to 232). The risk of joint bleeding was estimated among the trial participants; at a transgene-derived factor VIII level of 5 IU per deciliter measured with chromogenic assay, we expected that participants would have 1.0 episode of joint bleeding per year. At 2 years post infusion, no new safety signals had emerged and no new serious adverse events related to treatment had occurred   Miesbach : Dtsch Arztebl Int. 2022 Dec 27;119(51-52):887-894.   Data from non-randomized phase 1 to phase 3 trials reveal an adequate expression of factors VIII and IX in patients with mostly severe hemophilia A or B. Even though they were no longer receiving prophylactic treatment, most patients experienced a considerable reduction, by 53% to 96%, in the number of bleedings compared to previous therapy. Persistently elevated factor levels have been described for up to six years in hemophilia A and up to eight years in hemophilia B. The most common side effect of gene therapy is an inflammatory response with elevated alanine aminotransferase levels (17% to 89%, depending on the study), which may be associated with a reduced clotting factor level and requires treatment with transient immunosuppression. Gene therapy for hemophilia holds out the prospect of freedom from hemorrhage without the need for regular treatment with drugs. The various steps that need to be carried out in gene therapy should be coordinated in a graded and partly overlapping integrated care model (a so-called hub-and-spoke model). Electronic platforms should be used for data acquisition and transmission.   Samuelson Jones & George: Annu Rev Med. 2023 Jan 27:74:231-247.   Importantly, despite repeated proof-of-concept success in current hemophilia gene therapy, stable, durable FVIII or FIX expression able to ameliorate bleeding in all patients is an unrealized hope. This defines the development goals of the next generation of gene-based therapies for hemophilia.   *Valentino et al: J Thromb Haemost. 2023 Sep;21(9):2354-2361   In 2022, the National Hemophilia Foundation submitted a citizen petition (docket number FDA-2022-P-1444-0001) to the FDA requesting that a risk evaluation and mitigation strategy (REMS) be required as a condition of approval for both valoctocogene roxaparvovec and etranacogene dezaparvovec. Other organizations including the World Federation of Hemophilia, Hemophilia Federation of America, and the European Haemophilia Consortium joined this effort submitting separate but supportive statements to the FDA. However, the FDA reasoned that the requirements for the REMS for etranacogene dezaparvovec were not met, and it has received marketing authorization from the FDA without the requirement for the REMS. While this may be the case for people living with hemophilia B, for whom the benefit to risk equation for gene therapy is generally favorable [[58]], it may not be the same for people with hemophilia A when considering gene therapy. Standard and extended half-life products for the prevention of bleeding for people living with either hemophilia A and B may provide very good outcomes but at a substantial burden of treatment and also fail to prevent all bleeding.   Another approach is a restrictive introduction, such as a conditional marketing authorization in which a medicine fulfills an unmet medical need but there is still a need for comprehensive safety, efficacy, and quality data generation after approval [[62]]. Such approvals are granted for 1 year but can be renewed annually. Compliance with specific obligations with defined timelines is a necessary prerequisite for continued authorization [   [63]]. This mechanism was utilized in the case of onasemnogene abeparvovec, an AAV9 gene therapy for spinal muscular atrophy [[64]].   Here, we recommend that the following steps be taken by the hemophilia community to ensure the safety and optimal outcomes for PwH who choose to receive a gene therapy product:   1.Training and education must be provided for physicians and HCPs on gene therapy and the management of PwH who receive a gene therapy product 2.Training and education on shared decision making must be provided for physicians and HCPs who will evaluate, administer, and follow PwH who are candidates to receive a gene therapy product [ 3.Facilities administering valoctocogene roxaparvovec and etranacogene dezaparvovec must receive adequate training and instruction on all aspects of gene therapy [ 4.Valoctocogene roxaparvovec and etranacogene dezaparvovec must only be administered at or in conjunction with a hemophilia treatment center with knowledge and expertise in evaluating, administering, and managing PwH who have received investigational gene therapy products [ 5.Individuals receiving valoctocogene roxaparvovec and etranacogene dezaparvovec must be enrolled in the global gene therapy registry initiated by the World Federation of Hemophilia in order to collect robust data, including adverse events of special interest [ 6.Educational support should be developed in a transparent and unbiased way to facilitate learning by PwH so that they may participate in shared decision making  7.Formal collaboration between the relevant national hemophilia patient organizations and the centers administering gene therapy on the provision of education and information should be ensured so that the PwH is ready to fully participate in a shared and informed decision-making process. 8.Work to ensure that postmarket studies, registries, and future registrational studies take into consideration principles of health equity in their design.   *Baas: J Thromb Haemost. 2023 Mar;21(3):413-420. (Ethics)   Based on our analysis of the literature, we identified 3 ethical themes. The theme Living up to expectations describes the existing hopes for gene therapy and the unlikelihood of the currently approved product becoming a permanent cure. In the theme Psychosocial impacts, we discuss the fear that gene therapy will impact the identity of people with hemophilia and their need for psychosocial support. The theme Costs and access discusses the expected cost-effectiveness of gene therapy and its implications on accessibility worldwide. We conclude that it may be necessary to change the narratives surrounding gene therapy, from describing it as a cure to describing it as one of the many treatments that temporarily relieve symptoms and that there is a need to reevaluate the desirability of gene therapy for hemophilia, given the availability of other treatments. *Kumar: J Thromb Haemost. 2024 Jan;22(1):23-34    Of note, multiple preclinical studies using platelet-specific lentiviral gene delivery to hematopoietic stem cells in hemophilia have demonstrated promising results with therapeutic levels of neo-protein that rescue the hemorrhagic bleeding phenotype and induce antigen-specific immune tolerance. Further studies using ovalbumin as a surrogate protein for platelet gene therapy have shown robust antigen-specific immune tolerance induced via peripheral clonal deletions of antigen-specific CD4- and CD8-T effector cells and induction of antigen-specific regulatory T (Treg) cells. This review discusses platelet-targeted gene therapy, focusing on immune tolerance induction.   Shah: Curr Med Res Opin. 2023 Feb;39(2):227-237   Bayesian and Frequentist linear mixed