Juliana Biondo, MD: Bispecific mAbs and FVIII Gene Therapy for Hemophilia A


Dr. Juliana Biondo discusses the exciting FDA approval of Roctavian and how it compares with other treatment options like Hemlibra.

Juliana Biondo, MD: Bispecific mAbs and FVIII Gene Therapy for Hemophilia A

Juliana Largrasta Biondo, MD

The positive phase 3 data for Roctavian (valoctocogene roxaparvovec-rvox) supported the US Food and Drug Administration (FDA) approval, though they are limited to a specific population of adults with hemophilia A who meet certain criteria.1

The safety, efficacy, predictability, and durability impact of novel gene therapies, such as Roctavian, will be better understood through future research, Juliana Lagrasta Biondo, MD, the executive director of Oncology/Hematology at Genentech, explained in a written interview with HCPLive.

Findings of the factor VIII (FVIII) therapy demonstrated an 80% reduction in annualized bleed rate (ABR) as well as a 98% reduction in clotting factor use, however, the unprecedented bleed control is accompanied by an association of liver abnormalities in approximately 80% of patients.2

Biondo discussed the current treatment options available for hemophilia A, and how effectiveness may vary compared between therapies and patient populations, with a specific focus on Hemlibra (emicizumab-kxwh). The prophylaxis treatment was approved by the FDA 5 years ago for significantly controlling bleeding episodes and has been a primary option for this patient population.

HCPLive: While the FDA approved Roctavian for adults with hemophilia A, the novel gene therapy doesn’t come without concerns regarding the predictability and durability of the treatment over time. Could you elaborate on these concerns and how they may impact its potential adoption as a treatment for hemophilia A?

Biondo: Genentech recognizes the promise of gene therapy and shares in the community’s excitement for this novel therapeutic approach.

The availability of Roctavian represents a step forward in incorporating an adeno-associated virus (AAV)-mediated gene therapy into the clinical care of patients with hemophilia A. However, current data are only available in a select population of adults with hemophilia A - those without a prior history of factor VIII inhibitors, without detectable immunity to AAV5 capsid, and without active liver disease.

Future research efforts will add to the medical community’s understanding of the impact of each gene therapy’s unique characteristics, unique proprietary gene of interest, different capsids, and different trial designs. Therefore, the clinical safety and efficacy of each gene therapy product will need to be studied and evaluated individually and each may demonstrate different safety, efficacy, predictability, and durability profiles.

Can you provide an overview of the current treatment options available for patients with hemophilia A?

For people with hemophilia A that develop factor VIII inhibitors, one option is to infuse with a bypassing agent (BPA), either on-demand (episodic) or as prophylaxis, to control bleeding.  However, this approach may provide variable bleeding control and may be less predictable than factor VIII replacement therapy in people with hemophilia A without inhibitors.

Likewise, BPA must be administered every-other day for routine prophylaxis. After preparing the medicine, these infusions typically take about 45 minutes, which can require frequent vein access and the long-term use of a device surgically implanted into a vein for some patients.

For people without factor VIII inhibitors, factor VIII replacement therapy and Hemlibra have been the standard of care. Therapeutic options requiring intravenous infusions several times a week can create a substantial treatment burden for patients and their families, especially for those with infants and young children, who may require central venous access.

Hemlibra was designed to overcome these challenges. Hemlibra is currently the only approved medicine for people with hemophilia A with or without factor VIII inhibitors that can be self-administered subcutaneously once weekly, every 2 weeks, or every 4 weeks.

It has proven efficacy and safety with long-term data for a broad range of people with hemophilia A, regardless of factor VIII inhibitor status, age, gender, or disease severity.

How does Hemlibra compare with traditional factor VIII replacement therapy in terms of efficacy and safety?

The overall efficacy and safety profile of Hemlibra has been demonstrated in the HAVEN studies, one of the largest pivotal trial programs in hemophilia A.

In the HAVEN 3 study, patients who received Hemlibra prophylaxis experienced significant reductions in treated bleeds when compared with no prophylaxis and also when compared with prior factor VIII prophylaxis treatment in an intra-patient comparison.

In an arm of HAVEN 3, people who had previously received factor VIII prophylaxis switched to once-weekly Hemlibra prophylaxis (n = 48), allowing for an intra-patient comparison of 2 prophylaxis regimens.

This analysis showed Hemlibra is the first medicine to demonstrate a statistically significant reduction of 68% in treated bleeds compared with prior factor VIII prophylaxis treatment.

The most common adverse reactions occurring in 10% or more of those treated with Hemlibra in pooled studies (n = 391) were injection site reactions (n = 85), headache (n = 57), and arthralgia or joint pain (n = 59).


  1. Grossi G. Roctavian Receives Approval by the FDA for Severe Hemophilia A. HCPLive. June 29, 2023. https://www.hcplive.com/view/roctavian-receives-approval-by-the-fda-for-severe-hemophilia-a
  2. Grossi G. Margaret Ragni, MD: Liver Abnormalities in Hemophilia A Gene Therapy Require Close Monitoring. HCPLive. June 30, 2023. https://www.hcplive.com/view/margaret-ragni-liver-abnormalities-hemophilia-a-gene-therapy-require-close-monitoring
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