What side effects are associated with this type of intervention?

Gene therapy for Hemophilia A, such as Valoctocogene Roxaparvovec, can lead to side effects including liver enzyme elevations, immune responses against the viral vector, and potential long-term risks that are still being studied. Prophylactic corticosteroids, used to manage immune responses, can cause side effects such as weight gain, hypertension, hyperglycemia, osteoporosis, and increased risk of infections. Combining these treatments aims to balance the benefits of sustained Factor VIII production with the management of immune-related side effects.

What prior FDA approvals exist?

The FDA has approved several treatments for Hemophilia A that focus on factor VIII production. Notably, recombinant factor VIII products like Kogenate and BAY 81-8973 (Kovaltry) have been approved for their efficacy in managing bleeding episodes. Additionally, extended half-life products such as rFVIII-Fc (Eloctate) have been approved, which fuse factor VIII with the Fc domain of immunoglobulin to prolong its activity. While gene therapy approaches like valoctocogene roxaparvovec are still under investigation, these existing treatments provide a foundation for managing Hemophilia A through enhanced factor VIII production and stability.

What other types of research exist?

Promising alternatives to Valoctocogene Roxaparvovec for Hemophilia A treatment in 2024 include: 1) Etranacogene Dezaparvovec, a gene therapy for Hemophilia B that may have implications for Hemophilia A; 2) Emicizumab, a bispecific antibody that mimics the function of Factor VIII; and 3) Fitusiran, an RNA interference therapy that targets antithrombin to enhance thrombin generation. These treatments are in various stages of clinical trials and have shown potential in managing Hemophilia A.

← Back to Search

Gene Therapy

Gene Therapy for Hemophilia A (GENEr8-3 Trial)

Phase 3

Waitlist Available

Research Sponsored by BioMarin Pharmaceutical

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Males ≥ 18 years of age with hemophilia A and residual FVIII levels ≤ 1 IU/dL as evidenced by medical history, at the time of signing the informed consent

Must have been on prophylactic hemophilia therapy for at least 12 months prior to study entry

Must not have

Significant renal dysfunction or liver dysfunction, infection or history of hepatic malignancy

Evidence of any bleeding disorder not related to hemophilia A

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline to week 52

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial tests a new gene therapy combined with anti-inflammatory medication for patients with severe hemophilia A. The treatment aims to help their bodies produce a necessary clotting protein and reduce inflammation.

Who is the study for?

This trial is for adult males with severe hemophilia A, who have been on prophylactic therapy for at least a year and have had significant exposure to FVIII treatments. They must not have any history of inhibitors to FVIII and agree to use contraception post-infusion. Those with antibodies against the treatment vector, active infections, immune disorders, or unrelated bleeding disorders cannot participate.

What is being tested?

The study tests valoctocogene roxaparvovec's effectiveness and safety in treating severe hemophilia A when used alongside preventive steroids. It aims to see if this gene therapy can reduce bleeding episodes by providing a functional copy of the faulty gene causing hemophilia.

What are the potential side effects?

Potential side effects may include reactions related to the body's immune response against the viral vector used in gene therapy or complications from steroid use such as increased infection risk, mood changes, elevated blood sugar levels, and possible organ inflammation.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I am a male over 18 with severe hemophilia A.

Select...

I have been on preventive treatment for hemophilia for at least a year.

Select...

I have been treated with FVIII or cryoprecipitate for at least 150 days.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I do not have severe kidney, liver problems, infections, or a history of liver cancer.

Select...

I have a bleeding disorder that is not hemophilia A.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline to week 52

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline to week 52

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline to week 52 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change From Baseline in FVIII Activity as Measured by Chromogenic Substrate Assay at Week 52.

Secondary study objectives

Change From Baseline in Annualized Utilization of Exogenous FVIII Replacement Therapy in EEP

Change From Baseline in Haemo-QoL-A Quality of Life: Consequences of Bleeding Domain Score, at Week 52

Change From Baseline in Haemo-QoL-A Quality of Life: Physical Functioning Domain Score, at Week 52

+4 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

1Treatment groups

Experimental Treatment

Group I: valoctocogene roxaparvovecExperimental Treatment1 Intervention

Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg with prophylactic corticosteroids

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

valoctocogene roxaparvovec

2015

Completed Phase 2

~20

0 / 5Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Gene therapy for Hemophilia A, such as Valoctocogene Roxaparvovec, introduces a functional Factor VIII gene into the patient's cells, enabling endogenous production of Factor VIII. This addresses the underlying genetic deficiency and offers a long-term treatment solution. Prophylactic corticosteroids are used alongside to manage the immune response, minimizing the risk of gene rejection. This combination is crucial for Hemophilia A patients as it reduces the need for frequent factor replacement therapies, potentially offering a more sustainable and effective treatment, thereby improving their quality of life.

[Therapeutic innovations for hemophilia].Glanzmann's thrombasthenia: pathogenesis, diagnosis, and current and emerging treatment options.