NEW YORK, June 26, 2025 
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• 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
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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
[email protected]. 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.
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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.