Dear Hemophilia B Community,

We are writing to share an important update on the availability of HEMGENIX® (etranacogene dezaparvovec-drlb).

CSL is currently experiencing a temporary global stockout of HEMGENIX® that will result in delays in treatment for some individuals in countries with established commercial access.

We want to be very clear that this situation is not related to the safety or effectiveness of HEMGENIX®. Rather, it reflects the complexity of manufacturing gene therapies, and our commitment to adhering to the highest regulatory and quality standards for the people we serve. We are working with regulatory authorities on strategies to ensure stable ongoing supply for HEMGENIX® while preserving our high-quality standards.

We know that this update may raise questions and that’s completely understandable. What we want you to know is that our highest priority, as always, is ensuring that eligible individuals have the information they need to determine if HEMGENIX® is right for them, and that when they do, HEMGENIX® is available in accordance with the highest standards. We remain fully committed to delivering this innovative, one-time gene therapy to the hemophilia B community and continue to have strong confidence in HEMGENIX®.

​We understand the careful thought and planning that go into every individual decision about gene therapy treatment. We deeply value our long‑standing partnership of trust with the hemophilia B community and will continue to keep you updated to ensure people with hemophilia B and their healthcare providers are informed and supported as they plan their hemophilia care needs.

For further information, please visit our contact page on CSL.com here:
https://www.csl.com/contact.
​
Sincerely,
Dr. Deborah Long,
SVP, Medical Affairs

Microhealth, the leading global app in digital hematology, is launching a new digital health
initiative, the PULSE (Period Understanding and Logging of Symptoms for
Empowerment) Pilot in the United States to address a critical gap in bleeding disorders
care: individuals are undertreated due to the normalization of menstrual bleeding, leading
to gaps in access to appropriate treatment and care.

The goal of the PULSE Pilot is to inform a potential expansion of the existing bleed log
within the Microhealth Bleeding Disorders app, specifically to capture menstrual bleeding
and related symptoms more effectively, as well as patient-reported outcomes.
PULSE Pilot volunteers will securely log menstrual cycles and related symptoms with
active consent. Microhealth will collect data in alignment with company data practices,
de-identify and aggregate it, and use it to inform future app development and quality
improvement. This is not a clinical research study. Enrollment is available for individuals in
the United States who menstruate and have a confirmed bleeding disorder diagnosis or are
suspected of having a bleeding disorder. Volunteers can participate regardless of current
treatment or medication status.

For over 15 years, Microhealth Digital Hematology has been an internationally trusted, free
digital tool for the bleeding disorders community worldwide. It lets individuals track bleeds,
symptoms, treatments, physical activity, and health experiences in one place; empowering
them to own their data, advocate for themselves, and optionally connect with Hemophilia
Treatment Centers. The Microhealth Bleeding Disorders app provides care teams with free,
real-time, patient-reported data that reflects their individual lived experience.

With the launch of the PULSE Pilot, Microhealth Digital Hematology aims to make
individuals' menstrual experiences more recognized and valued.

Interested in volunteering for PULSE? Please scan the QR code or visit
https://forms.gle/p8eu9FRV8XZFkMDP6 to join this critical effort.

For further information, please contact Microhealth Community Digital
Advocates Nandini Pethe at Nandini.Pethe@Microhealth.com or Michelle
Cecil at Michelle.Cecil@Microhealth.com. For more information about
Microhealth, visit Microhealth.com.

​We are pleased to announce an important update to the IDELVION Connect Copay Program.* In recognition of the ongoing needs of the patient community and our commitment to providing meaningful support, we are increasing the maximum eligible out-of-pocket copay assistance from $12,000 to $20,000 per patient. To enroll, patients and Specialty Pharmacies are encouraged to contact IDELVION Connect at 1-800-676-4266.
 
What is Changing

• Effective, January 1, 2026, CSL has increased the out-of-pocket IDELVION copay coverage up to $20,000 per year for each eligible patient. 

 
What is Not Changing

• IDELVION Copay Support Program helps eligible patients with commercial insurance by assisting with out-of-pocket expenses for IDELVION. Most patients with commercial insurance pay $0 out-of-pocket.
• Both patients and Specialty Pharmacies can contact IDELVION Connect at 1-800-676-4266 to inquire and/or process a copay coverage request.
• If a claim is disputed for any reason, the Specialty Pharmacy is responsible for contacting IDELVION Connect at 1-800-676-4266

 
If you have questions, feel free to contact IDELVION Connect at 1-800-676-4266.

Dear Hemophilia Community Partners,

On December 22, 2025, we shared the very sad news of the passing of a hemophilia A
participant with inhibitors in the marstacimab long-term extension trial. We remain
committed to transparency as we continue to assess what occurred.

The circumstances of this case are multi-factorial – including co-existing conditions, the
participant undergoing a urethroscopic surgical procedure, and use of a bypassing agent as
a concomitant therapy – and we are working to understand these elements as fully as
possible in this clinical setting. We plan to present this information as part of a late-breaker
session at the EAHAD congress on February 6.

As we previously shared, an independent external Data Monitoring Committee oversees all
ongoing marstacimab studies. Based on the current information available, the studies are
continuing as planned and the established benefit/risk profile of marstacimab remains
unchanged. We are continuing to review and assess information on this case as we always
do for our medicines, per established processes.

Thank you for your partnership and for your commitment to the hemophilia community.
​
Sincerely,
The Pfizer Hemophilia Team

Dear Hemophilia Community Partners, 

We are deeply saddened to share that a participant in the long-term extension trial  (B7841007) studying marstacimab in people living with hemophilia A or B with or without inhibitors has passed away in December 2025 following serious adverse events of  cerebellar infarction and subsequent cerebral hemorrhage. On behalf of everyone at Pfizer,  we extend our heartfelt sympathies to the participant’s family, friends, and all those  involved in their care. 

Pfizer, together with the trial investigator and the independent external Data Monitoring  Committee, are actively gathering information to better understand the complex, multi factorial circumstances surrounding this occurrence – including co-existing medical  conditions and concomitant medications – and the causality of the event. The individual, a  patient with hemophilia A and inhibitors, participated in the active treatment phase of the  parent study (B7841005) in 2022 prior to entering the long-term extension study in 2023.  Regulatory authorities and investigators have been informed. 

The safety and well-being of participants in our clinical trials remain our highest priority,  and we are committed to transparency and keeping the community informed as we learn  more. 

​Sincerely, 
​The Pfizer Hemophilia Team

NEW YORK, June 26, 2025 
​

• Study demonstrates superiority, showing both statistically significant and clinically meaningful reduction in annualized bleeding rate with a generally well-tolerated safety profile compared to on-demand treatment in patients 12 years and older
• HYMPAVZI was administered with a straightforward, once-weekly subcutaneous injection that required minimal preparation

Pfizer Inc. (NYSE: PFE) today announced positive topline results from the Phase 3 BASIS study (NCT03938792) evaluating HYMPAVZI™ (marstacimab) for adults and adolescents living with hemophilia A or B with inhibitors. The study met the primary endpoint and key secondary bleeding endpoints demonstrating the superiority of once-weekly subcutaneous HYMPAVZI in improving key bleeding outcomes compared to on- demand treatment in a patient population where less burdensome treatment approaches are needed.

Inhibitors, or antibodies, which neutralize factor replacement therapies and render them ineffective, may develop in people living with hemophilia. Inhibitors can be diagnosed with a blood test. Of the more than 800,000 people in the world living with hemophilia A or hemophilia B, approximately 20% of people with hemophilia A and 3% of people with hemophilia B are unable to continue taking factor replacement therapies because they develop inhibitors to FVIII (Factor VIII) and FIX (Factor IX) and these therapies no longer prevent or stop bleeding episodes.

“Patients with inhibitors tend to face frequent complications, and navigating the treatment landscape can introduce complexities and increase disease burden,” said Davide Matino, M.D., M.Sc., BASIS Principal Investigator, Associate Professor of Medicine, McMaster University. “The strong bleed reduction with HYMPAVZI compared to on-demand treatment in the Phase 3 BASIS study, coupled with its weekly administration method, offers exciting potential for these patients who are in critical need of treatment options.”

The BASIS trial demonstrated that prophylactic treatment with HYMPAVZI resulted in a statistically significant and clinically relevant reduction in annualized bleeding rate (ABR) of treated bleeds in people living with severe hemophilia A or hemophilia B with inhibitors. Forty-eight people living with hemophilia were treated with HYMPAVZI during a 12-month period versus an on-demand intravenous regimen with bypassing agents, administered as part of usual care in the six-month lead-in period. HYMPAVZI was superior to on-demand treatment with a 93% reduction in ABR over 12 months (ABR 1.39 vs ABR on-demand 19.78; p < 0.0001).
Superiority of HYMPAVZI was also demonstrated across all bleeding-related secondary endpoints—spontaneous bleeds, joint bleeds, target joint bleeds, and total bleeds.

HYMPAVZI was generally well-tolerated, consistent with the non-inhibitor cohort of the BASIS study and Phase 1/2 results. No deaths or thromboembolic events were reported.

“These encouraging results demonstrate HYMPAVZI’s potential to help people living with hemophilia A or B with inhibitors, meeting an important need for patients with antibodies that neutralize most factor-based prophylactic options used to manage bleeding episodes,” said Michael Vincent, M.D., Ph.D., Chief Inflammation & Immunology Officer, Pfizer. “HYMPAVZI represents Pfizer’s latest contribution in more than 40 years of working to advance hemophilia care, as a generally well-tolerated treatment option that could offer bleed protection with a straightforward, once-weekly subcutaneous administration in a pre-filled pen for patients with inhibitors, if approved in this patient population.”

Analyses of the full Phase 3 dataset from the inhibitor cohort of the BASIS study are ongoing, and additional data will be presented at upcoming medical meetings. Pfizer plans to discuss these data with regulatory authorities, with the goal of initiating regulatory filings for HYMPAVZI for the treatment of patients living with hemophilia with inhibitors.

Discovered by Pfizer scientists, HYMPAVZI has a mechanism of action that is differentiated from FVIII and FIX replacement treatments. Instead of replacing missing or insufficient clotting factors, HYMPAVZI is intentionally designed to target tissue factor pathway inhibitor (TFPI), one of the body’s natural mechanisms that inhibits the initiation of blood clotting. By targeting the Kunitz 2 domain of TFPI, HYMPAVZI may help re-establish balance between bleeding and blood clot formation with the goal of offering a combination of bleed protection, good tolerability, and straightforward administration.

Read more: ​https://www.pfizer.com/news/press-release/press-release-detail/pfizer-announces-positive-topline-phase-3-results

May 27, 2025
​
Dear members of the hemophilia community,

We are reaching out to share an important update about the integration of Spark Therapeutics into the
Roche Group and to reiterate the commitment to develop a gene therapy as well as other therapeutic
advances for people with hemophilia.

In 2019, Spark Therapeutics became a member of the Roche Group. With its extensive resources and
worldwide reach, including Genentech in the United States, this partnership aimed to accelerate the
discovery, development and delivery of potential gene therapies for more patients affected by a wide
range of genetic diseases, including but not limited to hemophilia.

On January 30, 2025, Roche, in support of its commitment to address unmet medical needs through
cutting-edge science, announced that Spark will become fully integrated into the Roche Group. As a
result, in the U.S. Genentech will be the point of contact for the hemophilia A gene therapy program
going forward.

While this means that Spark Therapeutics will no longer operate as an independent company, its
expertise and knowledge as a leader in gene therapy will be folded into Roche and Genentech, and it will
continue in research and manufacturing of medicines. This integration of Spark into the Roche Group
supports the long-standing ambition and commitment to provide multiple transformative and reliable
treatment options that can address the needs of all people with hemophilia A, their families, and
caregivers.

With this change, we want to reinforce that the Roche Group remains committed to discovering,
developing and commercializing innovative treatments for hemophilia.

In December 2024, we announced the decision to introduce an enhanced function factor VIII variant
(SPK-8011QQ) into the hemophilia A gene therapy program. This next-generation gene therapy program
is planned to be studied in a Phase 2b clinical trial sponsored by Roche and Genentech. More detailed
information about the program is available at the end of this letter.

For those who participated in the Phase 1/2 clinical trial of investigational dirloctocogene samoparvovec

(SPK-8011), your participation has been invaluable to advancing hemophilia A gene therapy. The long-
term follow-up study will continue, and you will continue to be followed as a study participant. We

encourage you to reach out to your clinical trial site with any questions you may have.
Our team wants to take a moment to express our deepest gratitude to you–the patients, families,
caregivers, advocacy group leaders, and healthcare providers. Over the years, you have shared your
experiences living with hemophilia, we have heard your hopes, questions and curiosities about gene
therapy, and you have actively engaged in clinical research–all of which has been essential in advancing
gene therapy for hemophilia forward.

Going forward, please direct any questions about the program or Spark integration, to Genentech at
infoadvocacyrelations-d@gene.com. We look forward to continuing this close collaboration through the
Genentech Patient Advocacy Relations team.

Sincerely,
Tessa Field, Spark Therapeutics, Director, Patient Advocacy
Gina Truslow, Genentech, Director, Patient Advocacy Relations


Phase 2b Hemophilia A Gene Therapy Clinical Trial

In line with the commitment to bring transformational therapies to patients, the Roche Group is
introducing an enhanced function factor VIII variant (SPK-8011QQ) into the hemophilia A gene therapy
program.

Current adeno-associated virus (AAV) gene therapies introduce the factor VIII gene to the liver aiming to
improve blood clotting for individuals with hemophilia A. By modifying the gene used in our
investigational gene therapy, we hope to achieve what the hemophilia community and healthcare
providers are looking for in one-time gene therapies, including improved hemostasis and lowered
treatment burden.

This decision builds on the results seen in the phase 1/2 study of investigational gene therapy
dirloctocogene samoparvovec (SPK-8011), which provided early insights to safety, predictability, and
durability using a low-dose approach. This study is investigational and efficacy and safety of
dirloctocogene samoparvovec has not been established. We will be leveraging the capsid (delivery
vehicle) and scientific learnings from the phase 1/2 program and introducing an enhanced function
factor VIII variant with the goal of developing a durable gene therapy that provides effective protection
against bleeds, without the need for factor VIII prophylaxis.

As we transition to the enhanced function FVIII variant, we have chosen to discontinue the phase 3
dirloctocogene samoparvovec gene therapy study. The phase 3 was stopped prior to dosing any
participants. Stopping the study was not related to safety concerns with dirloctocogene samoparvovec.
Participants in the phase 1/2 study of dirloctocogene samoparvovec will continue to receive long-term
follow-up and monitoring.
​
We are excited about the potential to advance hemophilia A gene therapy through a next-generation
program. This next generation gene therapy program is planned to be studied in a
Phase 2b clinical trial sponsored by Roche and Genentech. The phase 2b study will allow us an
opportunity to gather safety data before starting a larger phase 3 study of the enhanced function
variant.

Qfitlia approved as the first therapy in the US to treat hemophilia A or B with or without inhibitors

• Qfitlia (fitusiran), the first antithrombin-lowering therapy in hemophilia, offers consistent protection with as few as six injections a year via a prefilled pen or vial and syringe
• Unique mechanism helps reduce the frequency of bleeding episodes for people with hemophilia   

Paris, March 28, 2025. The US Food and Drug Administration (FDA) has approved Qfitlia (fitusiran), the first antithrombin-lowering (AT) therapy for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients (aged 12 or older) with hemophilia A or B with or without factor VIII or IX inhibitors. The approval is based on data from the ATLAS phase 3 studies that demonstrated clinically meaningful bleed protection as measured by annualized bleeding rates (ABR) across hemophilia patients with or without inhibitors.

Phil Gattone
President and CEO, National Bleeding Disorders Foundation
“Current treatment options can make people with hemophilia feel they need to choose between effective bleed control and convenient dosing schedules, leading to trade-offs when it comes to disease management. Qfitlia takes a novel approach to providing protection for people living with hemophilia while reducing the frequency of dosing for patients and their families.”

By lowering AT, a protein that inhibits blood clotting, Qfitlia helps increase thrombin generation to restore hemostasis in people with hemophilia. Qfitlia uses small-interfering RNA technology, which enables low treatment frequency, subcutaneous dosing, and low volume injections.

Brian Foard
Executive Vice President, Head of Specialty Care, Sanofi
“This approval highlights our commitment to advancing innovation and improving care for the rare blood disorders community. Qfitlia has the potential to meaningfully change the hemophilia landscape through effective bleed protection, infrequent dosing, and simplified administration. Our robust portfolio of hemophilia treatment options continues to grow as we focus on offering protection with reduced treatment burden that best fits an individual’s needs.”

Guy Young, MD
Director, Hemostasis and Thrombosis Center at Children's Hospital, Los Angeles
“Qfitlia delivers the fewest doses of any prophylactic therapy in hemophilia, and its unique mechanism allows it to be used to treat all types of hemophilia, including with inhibitors and hemophilia B, where unmet medical needs remain. By targeting antithrombin, which can be reliably measured with an FDA-cleared blood assay, Qfitlia is proven to help rebalance hemostasis and improve bleed rates and protection.”
In the ATLAS clinical development program, Qfitlia demonstrated low bleed rates across subgroups with as few as six injections a year. Key results include:

• Significant bleed reduction by 71% in ABR for patients without inhibitors treated with Qfitlia prophylaxis compared to clotting factor concentrate on-demand (estimated mean: ABR 9.0 vs. 31.4, respectively; p<0.0001) and by 73% in ABR compared to bypassing agent on-demand for patients with inhibitors (estimated mean: ABR 5.1 vs. 19.1, respectively; p=0.0006)
• Median observed ABR during the open-label extension study was 3.8 (IQR: 0.0–11.2) in patients without inhibitors and 1.9 (IQR: 0.0–5.6) in patients with inhibitors
• Median observed annualized spontaneous bleeding rate during the open-label extension study was 1.9 (interquartile range (IQR): 0.0-7.5) in patients without inhibitors and 1.9 (IQR: 0.0-3.7) in patients with inhibitors
• Nearly half of patients in the open-label extension study experienced one or fewer bleeds (31% 0 bleeds and 47% 0-1 bleeds)

There is also the potential for significant adverse reactions, including thrombotic events, acute and recurrent gallbladder disease, and hepatotoxicity. The most common adverse reactions (incidence >10%) are viral infection, nasopharyngitis, and bacterial infection.
In conjunction with the Qfitlia approval, the FDA also cleared the Siemens Healthineers’ INNOVANCE® Antithrombin assay as a companion diagnostic for Qfitlia to measure AT levels. Through the Qfitlia Testing Program with Labcorp, the FDA-cleared companion diagnostic will be available to patients prescribed Qfitlia to measure AT levels at no cost.

Qfitlia can offer the fewest doses of all prophylactic therapies, and it will have a comparable price to other prophylactic hemophilia treatments. HemAssist is launching alongside Qfitlia to provide comprehensive patient support services, including insurance and financial assistance as well as educational resources. This program is for patients prescribed Qfitlia or other hemophilia treatments from Sanofi’s portfolio.
The FDA granted Qfitlia Orphan Drug Designation for hemophilia A and B, Fast Track Designation for hemophilia A and B with and without factor VIII or IX inhibitors, and Breakthrough Therapy Designation for hemophilia B with factor IX inhibitors. A regulatory submission for Qfitlia for the treatment of hemophilia A or B in adults and adolescents with or without inhibitors is under review in Brazil. A regulatory decision is expected in China in the second half of 2025.

Read the full press release: https://www.news.sanofi.us/2025-03-28-Qfitlia-approved-as-the-first-therapy-in-the-US-to-treat-hemophilia-A-or-B-with-or-without-inhibitors

Kedrion Expands Ryplazim Distribution Network for PLGD-1 Patients 

FORT LEE, NJ., Mar. 20, 2025 /PRNewswire/ -- Kedrion Biopharma Inc. expands the distribution network for Ryplazim, a plasma-derived human plasminogen indicated for treating patients with plasminogen deficiency type 1 (PLGD-1). This expansion ensures timely access to this vital medication for patients across the US. PLGD-1 is a serious condition causing abnormal fibrin-rich lesions on mucosal surfaces, potentially leading to severe consequences like vision and hearing loss, airway obstruction, and infertility. Ryplazim, the only FDA approved therapy for PLGD-1 patients, offers an important treatment option. 

The recent FDA approval of the technology transfer and manufacturing capacity expansion of Ryplazim has enabled Kedrion to broaden its limited distribution network due to the increase of supply. This crucial step means more patients can have access to this treatment. The expanded network now includes a new distribution partner and two new specialty pharmacies.

CuraScript SD a provider of comprehensive distribution solutions, joins existing partners FFF Enterprises and The Alliance Pharmacy in distributing Ryplazim to patients with PLGD-1.

CVS Health and Soleo Health have been added to the list of specialty pharmacies carrying Ryplazim, increasing access points for patients. These pharmacies join Nufactor, enhancing the network to ensure wider availability.

This collaborative effort underscores Kedrion's commitment to improving patient care and broadening access to essential therapies. 

To learn more about accessing Ryplazim and its potential benefits, please visit www.Ryplazim.com.

Read the full press release: https://lnkd.in/ez242whw

This is a letter from Takeda Pharmaceuticals U.S.A., Inc on March 18 for the bleeding disorders community.

Global Discontinuation of HEMOFIL® M [Antihemophilic Factor (Human), Method M, Monoclonal Purified] and RECOMBINATE® [Antihemophilic Factor (Recombinant)]

Dear Valued Patient,
The purpose of this letter is to inform you that Takeda has decided to globally discontinue HEMOFIL® M
[Antihemophilic Factor (Human), Method M, Monoclonal Purified] and RECOMBINATE® [Antihemophilic Factor (Recombinant)].

This was not a decision we made lightly. As the treatment landscape evolves, we decided to discontinue these medicines as hemophilia patients continue to transition to alternate treatment options in the space, including those within our own hematology portfolio. It is important to note there is no quality issue with either HEMOFIL M or RECOMBINATE and that their safety and efficacy remains consistent with the product Prescribing Information.

We understand that this directly impacts you and are here to support the hemophilia community during this transition. We intend to supply HEMOFIL M and RECOMBINATE to patients already receiving these medicines until inventory is depleted or expired in mid-2026. Exact timing will vary based on potency and demand.

​Transitioning to Alternative Treatment
We recommend beginning to have discussions with your healthcare team to ensure ample time for creating a longer-term, alternative treatment plan.
​
For more than 70 years, we’ve pioneered innovations and worked tirelessly to improve the standard of care for hemophilia patients. We are proud to offer alternative treatment options within the Takeda factor VIII portfolio, namely ADVATE® [Antihemophilic Factor (Recombinant)] and ADYNOVATE® [Antihemophilic Factor (Recombinant), PEGylated], that may meet your individual needs and are similar to HEMOFIL M and RECOMBINATE. Please visit ADVATE.com and ADYNOVATE.com for more information.