Tomoyuki Igawa, PhD, is executive officer and head of the research division at Chugai Pharmaceutical. He joined Chugai in 2001 and has led its Biologics Research Department and Translational Research Division. He also served as CEO and research head of Chugai Pharmabody Research in Singapore. Igawa led the molecular design of emicizumab and the technologies for manufacturing bispecific antibodies efficiently. He invented several of Chugai’s antibody engineering technologies, which are used in satralizumab, crovalimab, and nemolizumab. He earned his PhD in chemical system engineering from the University of Tokyo.

Tomoyuki Igawa, PhD

Kunihiro Hattori, Takehisa Kitazawa, and Tomoyuki Igawa

The Albert and Mary Lasker Foundation presents the Lasker Awards to recognize research excellence, with a mission of improving health by accelerating support for medical research.¹ Takehisa Kitazawa, DVM, PhD, and Tomoyuki Igawa, PhD, shared the 2026 Lasker-DeBakey Clinical Medical Research Award with Kunihiro Hattori, PhD, for the discovery of emicizumab, which the 3 scientists developed at Chugai Pharmaceutical.² 

, the subcutaneous factor VIII (FVIII) mimetic has extended continuous prophylaxis to more patients with moderate and mild hemophilia A, according to a 

In the phase 3 HAVEN 1 trial, among patients aged 12 years or older with FVIII inhibitors previously receiving episodic bypassing agents, emicizumab prophylaxis reduced the rate of treated bleeds by 87% compared with no prophylaxis (95% CI, 72.3-94.3; P < .0001).² In 

, which enrolled 152 patients without inhibitors, treated-bleed rates were 96% and 97% lower with weekly and every-2-week dosing, respectively, compared with no prophylaxis, and no new FVIII inhibitors were reported.² Later trials extended evaluation to every-4-week dosing, nonsevere disease, and infants with severe hemophilia A.²

thrombotic microangiopathy and thromboembolism

, reported when a cumulative average of >100 U/kg/24 hours of activated prothrombin complex concentrate (aPCC) was given for 24 hours or more during emicizumab prophylaxis.³ The label advises monitoring for these events if aPCC is administered.³

In the following written interview, Kitazawa discusses how emicizumab changed care for patients with and without inhibitors and the unmet needs still facing the field, and Kitazawa and Igawa reflect on what its development offers researchers pursuing new therapeutic classes.

Q&A: Emicizumab, Inhibitors, and Unmet Needs in Hemophilia A

HCPLive: How has emicizumab changed prophylaxis in hemophilia A, particularly for patients with factor VIII inhibitors, and what unmet needs remain?

 At the time emicizumab drug discovery was initiated, factor VIII (FVIII) agents were the most effective treatment option for hemophilia A. However, because FVIII is recognized as non-self in people with hemophilia A, approximately one-third of patients develop an immune response to infused FVIII products, resulting in the development of FVIII-inhibitory alloantibodies, known as FVIII inhibitors. This represented one of the most critical issues in the treatment of hemophilia A.

FVIII inhibitors preclude the use of FVIII products and make bleeding difficult to control, because alternative treatments, known as bypassing agents, have shorter half-lives, are more costly than FVIII products, and are not always effective. Consequently, the development of FVIII inhibitors deprived people with hemophilia A and their families of a reliable therapeutic option and significantly impaired their QOL.

Emicizumab exerts its pharmacological activity regardless of FVIII inhibitors and does not induce FVIII inhibitors, because its amino acid sequence and molecular structure are totally different from those of the FVIII molecule. Consequently, emicizumab can not only substantially improve the QOL of people with FVIII inhibitors and their families, but also greatly reduce the fear of developing FVIII inhibitors among those without them.

For people without FVIII inhibitors, around the time emicizumab drug discovery was initiated, prophylactic treatment with regular administration of an FVIII product was beginning to be widely adopted in developed countries. Before then, treatment had consisted solely of on-demand therapy, in which an FVIII product was administered to achieve hemostasis after a bleed had occurred. Prophylactic treatment aimed to convert “severe disease” (defined as <1% FVIII activity relative to the normal standard) into “moderate disease” (defined as 1%–5% FVIII activity), and it typically reduced bleeding episodes from dozens per year in people with severe hemophilia A to only a few per year. However, this treatment required intravenous administration of an FVIII product 3 times per week. Although home treatment was available, intravenous injection was technically challenging. This was particularly burdensome not only for young boys with hemophilia A, who often feared needles, but also for their parents, who frequently had to administer injections despite the difficulty of accessing their children’s tiny veins.

Emicizumab is a subcutaneous formulation that does not require venous access. It therefore substantially reduces the technical burden of administration while also markedly reducing dosing frequency compared with FVIII products. Dosing can be selected from once weekly, once every 2 weeks, or once every 4 weeks instead of 3 times a week. As a result, the burden of home treatment has been greatly reduced. Extended half-life FVIII products are now available, and 1 of these can be administered as infrequently as once weekly; however, intravenous administration and venous access are still required.

Furthermore, a phase 3 clinical study demonstrated that emicizumab prophylaxis provides greater bleeding-prevention efficacy than prophylactic treatment with FVIII products. Importantly, as noted above, emicizumab can be effective not only in people without FVIII inhibitors but also in those with FVIII inhibitors.

Nevertheless, we recognize several remaining unmet medical needs:

Some people still experience bleeds requiring treatment with coagulation factor agents, either FVIII products or bypassing agents, even while receiving emicizumab.

Although the treatment burden has been reduced, a certain level of administration burden remains.

A genetic cure for hemophilia A has not yet been achieved.

We remain committed to the research and development of new therapies to further improve the lives of people with hemophilia and their families.

HCPLive: What lessons from emicizumab’s development could help researchers translate other biological insights into new therapeutic approaches?

Takehisa Kitazawa, DVM, PhD, and Tomoyuki Igawa, PhD:

 First, emicizumab was the first full-length recombinant therapeutic bispecific antibody, and it paved the way for the practical therapeutic application of bispecific antibodies. Although the concept of bispecific antibodies had long existed, their complex structures made recombinant commercial production extremely difficult. The first recombinant bispecific antibody therapeutic to reach the market was blinatumomab (Micromet and Amgen) in 2014, just 12 years ago. Blinatumomab consists of linked antibody fragments, whereas emicizumab, launched in 2017, was the first full-length therapeutic bispecific antibody to be marketed. Since 2020, full-length therapeutic bispecific antibodies have been introduced to the market one after another, meaning emicizumab led the way.

Second, emicizumab broke with the conventional paradigm regarding the mechanisms of action of therapeutic antibodies, thereby expanding their therapeutic potential and effectiveness. More than 100 therapeutic antibodies have been marketed to date and have contributed to the treatment of many diseases. With the exception of emicizumab, these therapeutic antibodies act either by neutralizing their target antigens or by depleting cells expressing those antigens. In other words, like the natural function of antibodies as part of the immune system, they act through “subtraction.”

Emicizumab is the first therapeutic antibody to act through “addition.” Rather than inhibiting or eliminating something, it adds a specific physiological function to the human body. Moreover, it has opened an unexplored path in the field of therapeutic antibodies by using an antibody molecule as an artificial substitute for a functional protein with a complex function.

Third, and above all, it is highly significant that an original idea, one many people might have considered far-fetched, was developed into an outstanding medicine that has transformed the lives of people with hemophilia A. Emicizumab will serve as a valuable precedent and encourage further efforts to create biologics that go beyond conventional boundaries in drug discovery.

Editor’s Note: This transcript has been edited for grammar and clarity using artificial intelligence tools. Disclosures for Takehisa Kitazawa, DVM, PhD, and Tomoyuki Igawa, PhD, include Chugai Pharmaceutical.

Albert and Mary Lasker Foundation. Mission. Accessed October 9, 2026. 

Flaumenhaft R. Kunihiro Hattori, Tomoyuki Igawa, and Takehisa Kitazawa share Lasker Award honors for revolutionary hemophilia A therapy. 

. 2026;136(18):e212215. doi:10.1172/JCI212215

Hemlibra. Prescribing information. Genentech Inc. Accessed October 9, 2026. 

https://www.gene.com/download/pdf/hemlibra_prescribing.pdf

Articles

Lasker Award winners Takehisa Kitazawa and Tomoyuki Igawa discuss prophylaxis gains, remaining unmet needs, and lessons for drug discovery.


How Emicizumab Changed Hemophilia A Prophylaxis, and What Comes Next

Kunihiro Hattori, Takehisa Kitazawa, DVM, PhD, and Tomoyuki Igawa

The Albert and Mary Lasker Foundation presents the Lasker Awards to recognize research excellence, with a mission of improving health by accelerating support for medical research.¹ The 2026 Lasker-DeBakey Clinical Medical Research Award went to Kunihiro Hattori, Takehisa Kitazawa, DVM, PhD, and Tomoyuki Igawa, PhD, for the discovery of emicizumab, a bispecific antibody which mimics the cofactor function of factor VIII (FVIII) in hemophilia A.² The 3 scientists developed the drug at Chugai Pharmaceutical and described its development in a Perspective published in 

, emicizumab has become a first-line prophylactic option for patients with or without FVIII inhibitors, according to a 

 Viewpoint on the award.² “Emicizumab has been a disruptive force in hemophilia A treatment,” Robert Flaumenhaft, MD, PhD, of Beth Israel Deaconess Medical Center, wrote in the Viewpoint.²

The clinical problem was well defined. Inhibitors develop in approximately 30% of previously untreated patients with severe hemophilia A, and standard half-life FVIII products require frequent intravenous infusions, often through central venous access devices in young children.² Emicizumab remains active in the presence of FVIII inhibitors and can be dosed subcutaneously as infrequently as every 4 weeks.²

Hattori conceived the idea in 2000 of an antibody able to take over the cofactor role of FVIII.² In the following written interview, Hattori explains why the team set out to replace the function of FVIII rather than the factor itself, Kitazawa describes the assay problem behind an early failed candidate, and Igawa discusses the optimization behind more than 2,400 antibody variants.

Q&A: Designing a Factor VIII Mimetic Bispecific Antibody

 What led your team to pursue a bispecific antibody mimicking factor VIII activity rather than replacing the missing factor?

 When considering the limitations of existing therapies for hemophilia A, including the poor quality of life (QOL) that remained in persons with FVIII inhibitors and the challenges in adhering to prophylactic treatment regimens due to the need for venous access, I believed that fundamentally improving treatment by modifying factor VIII itself would be difficult. Instead, I concluded that the optimal solution would be to replace the function of factor VIII with an entirely different molecule. Given my understanding of both blood coagulation mechanisms and antibody biology, I believed antibodies had the potential to achieve this.

 What were the main challenges in designing an antibody to bridge activated factors IX and X while retaining therapeutic properties?

 At the time we started this project, it had not been elucidated precisely how FVIIIa interacts with FIXa and FX, or how it structurally promotes FIXa-catalyzed activation of FX. The precise mechanism remains unresolved even today. Consequently, there was not even a clue as to how to define the molecular properties required for effective treatment. Dr. Hattori’s concept was fairly high-level with regard to very specific antibody profiles.

Under these circumstances, we had to select and develop an in vitro assay capable of “accurately” and “quantitatively” evaluating bispecific antibody activity, to use as a guide for identifying and optimizing the bispecific antibody. In other words, our first key challenge was to determine which type of assay to use in the course of creating a clinical candidate bispecific antibody.

Initially, we applied the standard plasma assay that was widely used to quantitatively predict the hemostatic activity of FVIII agents in persons with hemophilia. Using the plasma assay as a guide, we designed and improved bispecific antibodies and eventually identified a clinical candidate that demonstrated strong activity in the assay in 2005. However, this candidate did not demonstrate a clear hemostatic effect in our non-human primate bleeding model of acquired hemophilia A, indicating that this plasma assay was not useful for designing effective bispecific antibodies. In addition, we observed that this candidate induced bleeding symptoms in non-hemophilic animals. We subsequently found that it competed with FVIII.

We therefore re-explored and developed a series of different assays (reconstituted enzymatic assays) suitable for bispecific antibodies in terms of both efficacy and safety. We validated these assays by assessing the in vivo efficacy of bispecific antibody variants.

In summary, the first challenge in designing the desired bispecific antibody was to select and develop in vitro assays that could accurately evaluate its functional activity. This challenge was ultimately overcome through the process described above.

 article describes approximately 2,400 antibody variants. What mattered most in balancing activity, stability, and suitability for subcutaneous administration?

 After screening about 40,000 bispecific antibodies, we identified a lead bispecific antibody. It exhibited quite weak or insufficient factor VIII–mimetic activity, only comparable to that of the previously failed candidate, although it caused substantially less interference with coagulation.

Therefore, our first and most important priority was to substantially improve its biological activity while maintaining its safety profile.

Once this requirement had been met after examining about 700 variants, however, we found that other properties required for long-term, infrequent subcutaneous therapy had been substantially compromised. These included securing appropriate pharmacokinetics and subcutaneous bioavailability, achieving high solubility with low viscosity, and ensuring high physicochemical stability. The next key challenge was to improve these properties while maintaining the biological activity we had achieved. In addition, we had to address immunogenicity risk and establish technologies that would enable robust manufacturing of bispecific antibodies at an industrial scale. All of these attributes were essential for a viable pharmaceutical product.

The greatest challenge we faced during antibody engineering at this stage was that these properties were interdependent. A variant that enhanced activity often impaired other properties, such as pharmacokinetics, stability or solubility, and immunogenicity.

I believe the most important key to the success of emicizumab was that we tried to improve “all” the properties required to create a transformative medicine. Our persistent efforts conducting rigorous, multidimensional evaluations, carefully analyzing the resulting data from multiple perspectives, and identifying useful mutations and combinations of mutations one by one finally enabled the discovery of emicizumab after evaluating more than 2,400 variants.

Editor’s Note: This transcript has been edited for grammar and clarity using artificial intelligence tools.

Editors’ Note: Disclosures for Kunihiro Hattori, Takehisa Kitazawa, DVM, PhD, and Tomoyuki Igawa, PhD, include Chugai Pharmaceutical.

Hattori K, Kitazawa T, Igawa T. From biological insight to a new class of medicines for hemophilia A: the 2026 Lasker-DeBakey Clinical Medical Research Award. 

. Published online September 9, 2026. doi:10.1001/jama.2026.15612

Lasker Award winners Kunihiro Hattori, Takehisa Kitazawa, and Tomoyuki Igawa recount the 2400 variants behind the drug.