Six biotech companies leading the charge in hemophilia treatment

Hemophilia is a rare, genetic disorder in which the blood does not clot enough to make bleeding slow down or stop. This is because patients with hemophilia do not have the normal amount of clotting factors, which usually work with platelets to form blood clots that control bleeding. The two main types of the disorder are called hemophilia A and hemophilia B; hemophilia A  happens when someone does not have enough clotting factor VIII, and hemophilia B happens when someone does not have enough clotting factor IX. 

Fortunately, there are a number of biotech companies developing treatments – from gene therapies to RNAi therapies – for both types of the disorder. In this article, we take a look at six hemophilia companies leading the way in the field.

Alnylam Pharmaceuticals

• Technology: RNAi therapies 
• Lead hemophilia product: Qfitlia (fitusiran)
• Recent news: Received FDA approval for Qfitlia for the treatment of hemophilia A or B

A pioneer in RNA interference (RNAi) therapies, Alnylam Pharmaceuticals has seen great success when it comes to developing these types of medicines for a range of diseases, including hemophilia. 

The company’s therapies essentially work by using RNAi to “silence” or turn off the production of specific genes that cause or contribute to disease. RNAi is a natural biological process that regulates gene expression by “interfering” with messenger RNA (mRNA), which carries DNA’s instructions for making new proteins. Alnylam’s RNAi therapies mimic this process by delivering specially designed small interfering RNAs (siRNAs) that bind to target disease-causing mRNA and guide their destruction like a pair of molecular scissors.

In March 2025, Alnylam announced that the U.S. Food and Drug Administration (FDA) had approved its drug, Qfitlia (fitusiran), developed under a collaboration with Sanofi, for the treatment of hemophilia A or B. This marked the sixth Alnylam-discovered medicine using its RNAi therapeutic platform to be approved to date. Significantly, the therapy also became the first and only therapeutic to lower antithrombin (AT), a protein that inhibits blood clotting, with the goal of promoting thrombin generation to rebalance hemostasis and prevent bleeds. This enables the drug to treat both types of hemophilia, whereas most other hemophilia treatments on the market can only address one disease subtype because they work by replacing a specific clotting factor. 

Be Biopharma 

• Technology: Engineered B cell medicines
• Lead hemophilia candidate: BE-101
• Recent news: Closed an $82 million financing round 

Be Biopharma is focused on developing engineered B cell medicines to improve the lives of patients who are living with hemophilia B, as well as other genetic diseases, cancer, and other serious conditions. The company says that B cell therapies have the potential to be durable, allogeneic, redosable, and administered without toxic conditioning, making them an extremely promising class of therapeutics. 

The company’s lead program is called BE-101 and is designed to sustain Factor IX levels in adults with hemophilia B. It became the first engineered B cell medicine to enter clinical trials for hemophilia B after the FDA cleared Be Bio’s Investigational New Drug application (IND) in May 2024. Furthermore, the FDA has also granted orphan drug designation for the candidate. It is currently being tested in a phase 1/2 study intended to evaluate the safety and clinical activity of a single IV dose in adults with moderately severe or severe hemophilia B. 

In October 2024, the hemophilia company announced that it had closed an $82 million financing round, which it said will help advance BE-101 to clinical proof of concept, as well as progress its second development candidate, BE-102, for another severe genetic disease called hypophosphatasia.

BioMarin

• Technology: AAV-based gene therapy
• Lead hemophilia product: Roctavian (valoctocogene roxaparvovec-rvox)
• Recent news: Presented positive seven-year follow-up phase 2 data for ROCTAVIAN

Founded in 1997, BioMarin already has eight marketed products, including an adeno-associated virus (AAV) vector-based gene therapy called Roctavian (valoctocogene roxaparvovec-rvox) for the treatment of adults with severe hemophilia A. The one-time infusion works by delivering a functional gene that is designed to enable the body to produce factor VIII on its own, reducing the need for ongoing prophylaxis.

Roctavian was first approved by the European Commission (EC) in August 2022. It then received the green light from the FDA in June 2023 based on positive data from a global phase 3 study, which was the largest phase 3 trial of any gene therapy in hemophilia to report more than three years of data. Of the 134 patients who received the gene therapy in the study, 112 had baseline annualized bleeding rate (ABR) data collected prospectively during a period of at least 6 months on factor VIII prophylaxis. These patients experienced a mean ABR reduction of 52% after receiving Roctavian compared to their baseline ABR while receiving routine prophylaxis (2.6 bleeds per year versus 5.4 bleeds/year, respectively). 

Meanwhile, in February 2024, BioMarin presented new seven-year follow-up phase 2 results for Roctavian at the 2024 European Association for Haemophilia and Allied Disorders, demonstrating that median factor VIII activity at year seven remained in the mild hemophilia range and mean ABR for treated bleeds over the full follow-up period decreased by 96% from baseline for adults with severe hemophilia A. 

Expression Therapeutics 

• Technology: LV-based gene therapy 
• Lead hemophilia candidate: ET3 gene therapy
• Recent news: Announced promising phase 1 results for ET3 gene therapy 

Cell and gene therapy company Expression Therapeutics is focused on advancing curative therapies for hemophilia A, as well as developing innovative oncology solutions targeting neuroendocrine tumors and neuroblastoma. The company’s lead product for hemophilia A – ET3 – is an ex vivo hematopoietic stem cell (HSC) lentiviral vector (LV)-based gene therapy that works with cells derived from the patient (autologous cells). 

For the therapy, white blood cells are harvested from the blood of a patient through a process called apheresis. Then, hematopoietic stem and progenitor cells are enriched in the laboratory through a process called CD34+ selection. Subsequently, the CD34+ cells are genetically modified using the company’s LV-factor VIII vector and then transplanted back into the patient through an infusion. The therapy then engrafts back into the stem cell compartment within the bone marrow and provides a continuous supply of functional FVIII to the bloodstream.

In December 2024, Expression Therapeutics announced promising phase 1 results for its hemophilia gene therapy, demonstrating that no spontaneous bleeding events occurred in any of the five participants in the study. These results were consistent with measured FVIII levels, which increased from undetectable to levels predicted to produce therapeutic efficacy in all five patients. Additionally, except for neutropenia and thrombocytopenia, which were expected, no adverse events greater than grade 2 occurred in any participant. 

Sangamo Therapeutics

• Technology: Gene therapy
• Lead hemophilia candidate: Giroctocogene fitelparvovec
• Recent news: Announced positive topline phase 3 results for giroctocogene fitelparvovec

Genomic medicine company Sangamo Therapeutics developed the hemophilia A candidate giroctocogene fitelparvovec, a gene therapy that contains a bio-engineered AAV6 capsid and a modified B-domain deleted human coagulation factor VIII gene, as part of a collaboration agreement with Pfizer. In late 2019, Sangamo transferred the manufacturing technology and the IND application to Pfizer. Under the agreement, Pfizer assumed responsibility for pivotal studies, any regulatory activities, and potential global commercialization of giroctocogene fitelparvovec.

The goal of the candidate is that a single infusion of giroctocogene fitelparvovec may allow patients to produce factor VIII themselves for an extended period of time, providing bleed protection and reducing the need for routine prophylaxis with intravenous (IV) infusions or injections. In July 2024, Pfizer announced positive topline results for the therapy from a phase 3 study as it hit its primary endpoint by showing a statistically significant mean reduction in ABR. The study also hit its key secondary endpoints, including 84% of participants maintaining factor VIII activity of more than 5% above their pre-dosed level.

However, Pfizer pulled out of the development deal with Sangamo in December 2024, meaning that Sangamo has now regained full rights to its gene therapy program. At the time of this announcement, Sangamo said that it intends to explore all options to continue to advance giroctocogene fitelparvovec, including seeking a potential new collaboration partner. 

uniQure

• Technology: (AAV5)-based gene therapy
• Lead hemophilia product: Hemgenix
• Recent news: Announced FDA approval of Hemgenix 

Developed by uniQure, in partnership with global biopharma CSL Behring, Hemgenix is a one-time adeno-associated virus serotype 5 (AAV5)-based gene therapy for patients with severe and moderately severe hemophilia B. The therapy contains the active ingredient etranacogene dezaparvovec, and is designed to deliver a copy of a gene that encodes the Padua variant of human coagulation factor IX through an intravenous infusion. Its mechanism of action is ultimately to elevate factor IX levels, which facilitates the formation of blood clots to restrict bleeding.

When the therapy was approved by the FDA in 2022, it became the first gene therapy for the treatment of adults with hemophilia B, intended for those who currently use factor IX prophylaxis therapy, have current or historical life-threatening hemorrhage, or have repeated, serious spontaneous bleeding episodes. The approval was based on results from the pivotal HOPE-B trial, which saw a durable improvement in mean factor IX levels, ultimately persuading 96% of the participants to quit routine prophylaxis. 

In May 2021, uniQure and CSL completed a licensing transaction providing CSL Behring with exclusive rights to commercialize and continue clinical development of Hemgenix globally, while uniQure would be responsible for the global manufacturing of the product at its licensed facility. 

Hemophilia: A difficult field for commercial success 

Despite several new breakthrough hemophilia treatments – namely gene therapies – now on the market, the companies that developed them appear to be struggling with uptake from patients and doctors. 

This is likely primarily down to the enormous price tags associated with gene therapies; uniQure’s Hemgenix became the most expensive drug in the world when it received approval, with a list price of $3.5 million. Meanwhile, BioMarin’s Roctavian came with a list price of $2.9 million. Although developers claim these therapies are worth it due to the fact that patients will only receive a one-time shot compared to lifelong treatment, the simple matter is that many patients still cannot afford it. Additionally, as experts stated during the 2023 American Society of Hematology’s (ASH) annual meeting, the logistical issues of manufacturing gene therapies, as well as other potential treatment advances, are also affecting their uptake. 

And because gene therapies have emerged as such an efficient way to treat both types of hemophilia, these issues are currently affecting how many companies are willing to develop hemophilia treatments. A pertinent example of this – as touched upon earlier in the article – is how Pfizer decided to pull out of its deal with Sangamo for its gene therapy candidate for hemophilia A, despite positive topline results. Furthermore, the pharma giant also recently decided to end global development and commercialization of its gene therapy Beqvez, less than a year after its FDA approval to treat hemophilia B.
Still, according to Grand View Research, the global hemophilia market size, which was estimated at $12.6 billion in 2022, is expected to grow at a compound annual growth rate (CAGR) of 6.6% from 2023 to 2030, with the major driving factors being gene therapy approval for hemophilia treatment and the presence of multiple other candidates in various pipeline phases.