What is the mechanism of action of this treatment?

The most common treatments for Duchenne Muscular Dystrophy (DMD) focus on genetic therapies that aim to restore the production of dystrophin, a protein crucial for muscle function. Gene therapy approaches, such as exon skipping and the use of viral vectors to deliver microdystrophin or minidystrophin genes, are designed to bypass or correct the genetic mutations causing DMD. Exon skipping drugs like eteplirsen, golodirsen, and casimersen work by allowing cells to skip over faulty exons in the dystrophin gene, enabling the production of a shorter but functional dystrophin protein. These treatments are significant for DMD patients as they target the root cause of the disease, potentially slowing its progression and improving muscle strength and function.

What side effects are associated with this type of intervention?

Gene therapy for Duchenne Muscular Dystrophy, such as the use of recombinant adeno-associated viral (rAAV) vectors carrying microdystrophin or minidystrophin genes, has shown promise but also presents potential side effects. These include immune responses, such as the presence of dystrophin-specific T-cells, which can hinder the effectiveness of the therapy. Other common treatments like eteplirsen, an antisense oligonucleotide, have side effects including balance disorder, vomiting, contact dermatitis, and upper respiratory tract infections. Ataluren, another treatment, can cause vomiting, decreased appetite, weight loss, and gastrointestinal discomfort. Overall, while these treatments offer hope, they also come with a range of possible adverse effects that need to be managed.

What prior FDA approvals exist?

The FDA has approved several genetic therapies for the treatment of Duchenne Muscular Dystrophy (DMD). These include eteplirsen, golodirsen, viltolarsen, and casimersen, which are exon skipping drugs designed to increase dystrophin production in patients with specific deletions in the DMD gene. Eteplirsen skips exon 51, golodirsen and viltolarsen skip exon 53, and casimersen skips exon 45. These treatments aim to produce a shorter but functional dystrophin protein, addressing the underlying genetic defect in DMD.

What other types of research exist?

Promising novel alternatives to gene therapy for Duchenne Muscular Dystrophy (DMD) patients include: 1) Eteplirsen, Golodirsen, and Viltolarsen, which are exon-skipping drugs designed to increase dystrophin production by skipping specific exons in the DMD gene. 2) Ataluren, an orally administered drug that promotes ribosomal read-through of nonsense mutations, allowing the production of functional dystrophin protein. 3) Glucocorticoid treatments, which are standard care for managing symptoms and slowing disease progression, though they come with potential side effects. These alternatives offer different mechanisms of action and can be considered based on individual patient genetic profiles and clinical conditions.

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Gene Therapy

Gene Therapy for Duchenne Muscular Dystrophy

Phase 3

Waitlist Available

Research Sponsored by Pfizer

Eligibility Criteria Checklist

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

Must have

Confirmed diagnosis of Duchenne muscular dystrophy by prior genetic testing

Ambulatory, as assessed by protocol-specified criteria

Must not have

Any prior treatment with gene therapy

Any of the following genetic abnormalities in the dystrophin gene: Any mutation affecting any exon between exon 9 and exon 13, inclusive; A deletion that affects both exon 29 and exon 30; A deletion that affects any exons between 56-71, inclusive.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up week 52

Awards & highlights

Pivotal Trial

Summary

This trial tests a gene therapy treatment for boys aged 4 to 7 with muscle problems. The treatment aims to fix the genetic issues causing their muscle problems. Participants will receive the treatment and be monitored for safety and effectiveness. The treatment involves using a specific gene therapy, which has been researched for its potential to correct muscle issues in children with muscle problems.

Who is the study for?

This trial is for boys with Duchenne muscular dystrophy (DMD) confirmed by genetic testing, who can walk and have been on a stable dose of steroids for at least 3 months. Boys with antibodies to AAV9, recent treatments increasing dystrophin expression, prior gene therapy, non-healed injuries affecting tests or certain genetic abnormalities in the dystrophin gene cannot participate.

What is being tested?

The study tests the safety and effectiveness of PF-06939926, a gene therapy for DMD. Participants are randomly assigned to receive either this gene therapy or a placebo in a blinded manner. Two-thirds will get the actual treatment while one-third receives placebo with an option to switch after one year.

What are the potential side effects?

Potential side effects may include immune reactions due to viral vector used in gene therapy (like fever or chills), liver enzyme elevations indicating stress on the liver, blood count changes suggesting bone marrow impact, and possible allergic responses.

Eligibility Criteria

Inclusion Criteria

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

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I have been genetically tested and confirmed to have Duchenne muscular dystrophy.

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I can walk and move around on my own.

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I have been on a stable dose of steroids for at least 3 months.

Exclusion Criteria

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

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I have never had gene therapy before.

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My genetic test shows a specific mutation in the dystrophin gene.

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I haven't taken any medication to boost dystrophin in the last 6 months.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ week 52

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~week 52

This trial's timeline: 3 weeks for screening, Varies for treatment, and 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 North Star Ambulatory Assessment (NSAA)

Secondary study objectives

Change from Baseline in distribution of mini-dystrophin expression in the muscle

Change from Baseline in mini-dystrophin expression level in muscle

Change from Baseline in serum creatine kinase (CK)

+6 more

Awards & Highlights

Pivotal Trial

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

Trial Design

2Treatment groups

Experimental Treatment

Group I: Cohort 2Experimental Treatment2 Interventions

Approximately one third of participants will be randomized to Cohort 2.

Group II: Cohort 1Experimental Treatment2 Interventions

Approximately two thirds of participants will be randomized to Cohort 1.

0 / 6Eligibility 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 Duchenne Muscular Dystrophy (DMD) focus on genetic therapies that aim to restore the production of dystrophin, a protein crucial for muscle function. Gene therapy approaches, such as exon skipping and the use of viral vectors to deliver microdystrophin or minidystrophin genes, are designed to bypass or correct the genetic mutations causing DMD. Exon skipping drugs like eteplirsen, golodirsen, and casimersen work by allowing cells to skip over faulty exons in the dystrophin gene, enabling the production of a shorter but functional dystrophin protein. These treatments are significant for DMD patients as they target the root cause of the disease, potentially slowing its progression and improving muscle strength and function.

From diagnosis to therapy in Duchenne muscular dystrophy.Mutation-Based Therapeutic Strategies for Duchenne Muscular Dystrophy: From Genetic Diagnosis to Therapy.