What side effects are associated with this type of intervention?

The most common treatments for Hemophilia A include factor VIII replacement therapy and gene therapy. For gene therapy, such as the BMN 270 trial, side effects can include immune responses to the viral vector used for gene delivery, which may lead to inflammation or other immune-mediated reactions. Other potential side effects include liver enzyme elevations, which require monitoring. For traditional factor VIII replacement therapies, side effects can include the development of inhibitors (antibodies) against factor VIII, allergic reactions, and infusion-related reactions such as headaches, fever, and chills.

What prior FDA approvals exist?

The FDA has approved several treatments for Hemophilia A, primarily focusing on recombinant factor VIII products. Notable approvals include rFVIII-Fc (Eloctate), which extends the half-life of factor VIII by fusing it with the Fc domain of immunoglobulin, and B-domain deleted recombinant factor VIII (e.g., Advate), which offers improved safety and efficacy. Additionally, gene therapy approaches like BMN 270 (valoctocogene roxaparvovec) are being studied to provide long-term solutions by introducing functional copies of the factor VIII gene, potentially reducing or eliminating the need for regular factor replacement therapy.

What other types of research exist?

Promising alternatives to BMN 270 for Hemophilia A patients include: 1) Adeno-associated viral (AAV) vectors for gene therapy, which have shown clinical efficacy in trials. 2) Recombinant factor VIII therapies, such as those involving fusion proteins or extended half-life products. 3) Exon skipping therapies, which aim to restore dystrophin expression and have shown promise in clinical studies. These alternatives offer potential advancements in treatment efficacy and patient outcomes.

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Gene Therapy

Gene Therapy for Hemophilia A (BMN 270-301 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

No previous documented history of a detectable FVIII inhibitor, and results from a Bethesda assay or Bethesda assay with Nijmegen modification of less than 0.6 Bethesda Units (BU) on 2 consecutive occasions at least one week apart within the past 12 months

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 not have

Liver cirrhosis of any etiology as assessed by liver ultrasound

Chronic or active hepatitis B

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 5 years

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing BMN 270, a new treatment for hemophilia A, to see if it can reduce bleeding episodes better than current treatments. It works by helping the body make more of a protein needed for blood clotting. BMN 270 has shown therapeutic levels of FVIII in mice and primates and normalization of bleeding in hemophilic mice.

Who is the study for?

This trial is for adult males with Hemophilia A who have very low levels of Factor VIII and have been on standard treatment for at least a year. They must not have had inhibitors to Factor VIII, significant liver issues, other bleeding disorders, or certain infections like HIV or hepatitis.

What is being tested?

The study tests Valoctocogene Roxaparvovec (BMN 270), a gene therapy compared to standard Factor VIII prophylaxis. It measures the number of bleeds without FVIII treatment over two years and checks how much external FVIII is used after receiving BMN 270.

What are the potential side effects?

Potential side effects are not detailed here but typically include immune reactions to the therapy, increased risk of blood clots due to changes in clotting factors, and possible liver-related issues.

Eligibility Criteria

Inclusion Criteria

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

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I have never had a detectable FVIII inhibitor and recent tests confirm this.

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I am a male over 18 with severe hemophilia A.

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

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I have been on preventive FVIII therapy for over a year.

Exclusion Criteria

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

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My liver has been diagnosed with cirrhosis through an ultrasound.

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I have chronic or active hepatitis B.

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I have active Hepatitis C.

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I have a bleeding disorder that is not hemophilia A.

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I have antibodies against AAV5.

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I do not have any active infections or conditions that weaken my immune system, including HIV.

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I have an active cancer other than non-melanoma skin cancer.

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I have had liver cancer in the past.

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I do not have any active infections or immune disorders, except HIV.

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I have severe liver problems.

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I have a condition that increases my risk of blood clots.

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I have had blood clots in my arteries or veins.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 5 years 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 Annualized Number of Bleeding Episodes Irrespective of Exogenous FVIII Replacement Treatment [Annualized Bleeding Rate (ABR) for All Bleeds] in EEP.

Secondary study objectives

Change From Baseline in Annualized FVIII Utilization in EEP.

Change From Baseline in FVIII Activity at Week 104

Change From Baseline in Haemo-QoL-A Quality of Life: Consequences of Bleeding Domain Score, at Week 104

+4 more

Other study objectives

Percentage of participants with treatment-related adverse events, as assessed by CTCAE v4.03 during years 2-5 following valoctocogene roxaparvovec infusion

Percentage of participants with treatment-related adverse events, as assessed by CTCAE v4.03 in the first 52 weeks following valoctocogene roxaparvovec infusion

Percentage of participants with treatment-related adverse events, as assessed by de novo development of FVIII inhibitors during years 2-5 following valoctocogene roxaparvovec infusion

+1 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 roxaparvovec Open LabelExperimental Treatment1 Intervention

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

valoctocogene roxaparvovec

2015

Completed Phase 2

~20

0 / 16Eligibility 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

The most common treatments for Hemophilia A include recombinant factor VIII (rFVIII) products, gene therapy, and investigational approaches like bispecific antibodies and anti-TFPI antibodies. rFVIII products work by replacing the deficient factor VIII, essential for blood clotting, thereby reducing bleeding episodes. Gene therapy, such as BMN 270, aims to introduce a functional copy of the factor VIII gene into the patient's cells, potentially providing a long-term solution by enabling the body to produce its own factor VIII. Bispecific antibodies, like Mim8, and anti-TFPI antibodies, like concizumab, work by mimicking or enhancing the function of factor VIII, promoting clot formation. These treatments are crucial for Hemophilia A patients as they help manage bleeding risks, improve quality of life, and reduce the need for frequent infusions.