What is the mechanism of action of this treatment?

The most common treatments for Duchenne Muscular Dystrophy (DMD) include exon-skipping drugs like eteplirsen, golodirsen, and viltolarsen. These drugs work by skipping specific exons in the DMD gene, allowing the production of a shorter but functional dystrophin protein. This is crucial for DMD patients because the absence of dystrophin leads to muscle degeneration and weakness. By partially restoring dystrophin production, these treatments aim to stabilize muscle function and slow disease progression, offering a significant improvement in quality of life for patients.

What side effects are associated with this type of intervention?

Exon-skipping therapies like Eteplirsen, Viltolarsen, and Casimersen are designed to increase dystrophin production in patients with DMD. Common side effects of these treatments include upper respiratory tract infections, injection site reactions, cough, fever, headache, and gastrointestinal issues such as nausea and abdominal pain. Renal toxicity is a significant concern, necessitating regular monitoring of kidney function through urine dipstick tests, serum cystatin C, and urine protein-to-creatinine ratio. Hypersensitivity reactions, including rash, itching, and hives, have also been reported.

What prior FDA approvals exist?

The FDA has approved several exon skipping therapies for the treatment of Duchenne Muscular Dystrophy (DMD). Eteplirsen, which targets exon 51, was one of the first to receive accelerated approval based on its ability to increase dystrophin production. Following eteplirsen, the FDA approved golodirsen and viltolarsen, which target exon 53, and casimersen, which targets exon 45. These therapies work by binding to specific exons of the dystrophin pre-messenger RNA, promoting exon skipping during RNA processing, and thereby allowing the production of a functional, albeit truncated, dystrophin protein. These approvals are based on surrogate endpoints like increased dystrophin levels, with ongoing trials required to confirm clinical benefits.

What other types of research exist?

Promising alternatives to Eteplirsen for DMD patients include: 1) Viltolarsen, another exon-skipping therapy targeting exon 53, which has shown increased dystrophin production and functional improvements. 2) Casimersen, targeting exon 45, which has received FDA approval based on increased dystrophin levels. 3) Ataluren, a small molecule promoting read-through of nonsense mutations, available in the EU for DMD caused by nonsense mutations. 4) Gene therapy approaches using microdystrophin or minidystrophin genes delivered via adeno-associated viral vectors, which are in advanced stages of clinical trials.

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Exon Skipping Agent

High-Dose Eteplirsen for DMD

Phase 3

Waitlist Available

Research Sponsored by Sarepta Therapeutics, Inc.

Eligibility Criteria Checklist

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

Must have

Be a male with an established clinical diagnosis of DMD and an out-of-frame deletion mutation of the DMD gene amenable to exon 51 skipping.

Ambulatory participant, able to perform TTRISE in 10 seconds or less at the time of screening visit.

Must not have

Major surgery within 3 months prior to randomization

Presence of any other significant neuromuscular or genetic disease other than DMD

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

Pivotal Trial

No Placebo-Only Group

Summary

This trial is testing eteplirsen, a medication for Duchenne Muscular Dystrophy (DMD). It targets patients with specific genetic mutations that can be treated by skipping exon 51. Eteplirsen helps the body make a protein needed for muscle function by bypassing a faulty part of the gene. Eteplirsen has been approved for treating DMD by skipping exon 51, allowing for the production of a functional dystrophin protein.

Who is the study for?

This trial is for boys with Duchenne Muscular Dystrophy who can walk independently and perform a timed test quickly. They must have specific genetic mutations treatable by skipping exon 51, stable breathing function, and be on steady corticosteroid doses. Boys using other DMD treatments or with kidney issues, recent major surgery, heart problems, or other serious diseases cannot join.

What is being tested?

The study tests two high doses of Eteplirsen (100 mg/kg and 200 mg/kg) against a standard dose (30 mg/kg) in boys with Duchenne Muscular Dystrophy. It's divided into two parts: first to see if the high doses are safe and then to find out which one works best compared to the standard dose.

What are the potential side effects?

Eteplirsen may cause side effects like injection site reactions, balance problems, nausea or vomiting. Since it's being tested at higher than usual doses, there might be new side effects that doctors will watch for carefully.

Eligibility Criteria

Inclusion Criteria

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

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I am a male diagnosed with DMD and have a specific genetic mutation treatable by exon 51 skipping.

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I can walk and complete a specific task in 10 seconds or less.

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I can walk on my own without help from devices.

Select...

Both of my biceps muscles are healthy and intact.

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I am 7 or older with stable lung function, or I am 4-6 years old and don't need a ventilator.

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I am a male with DMD due to a specific genetic mutation treatable by exon 51 skipping.

Select...

I can walk and complete a specific physical task in 10 seconds or less.

Select...

I can walk on my own without needing help or devices.

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My upper arm muscles are healthy and intact.

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I am 7 or older with stable lung function and don't need help breathing at night.

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I am between 4 to 6 years old and do not need a ventilator.

Exclusion Criteria

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

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I have not had major surgery in the last 3 months.

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I do not have any significant neuromuscular or genetic diseases other than DMD.

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My heart's pumping ability is reduced, or my heart rhythm test shows a delay.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Side effects data

From 2021 Phase 2 trial • 15 Patients • NCT03218995

100%

Pyrexia

83%

Nasopharyngitis

83%

Cough

67%

Rhinitis

67%

Vomiting

50%

Rash maculo-papular

50%

Ear infection

50%

Gastroenteritis

50%

Rhinorrhoea

50%

Diarrhoea

33%

Head injury

33%

Bronchitis

33%

Teething

33%

Influenza

33%

Lethargy

33%

Upper respiratory tract infection

33%

Fall

33%

Ear pain

33%

Iron deficiency

17%

Chalazion

17%

Rash

17%

Rash generalised

17%

Dermatitis diaper

17%

Dermatitis contact

17%

Faeces discoloured

17%

Laceration

17%

Constipation

17%

Abdominal pain

17%

Bronchiolitis

17%

Otitis media acute

17%

Procedural pain

17%

Vaccination complication

17%

Eczema

17%

Iron deficiency anaemia

17%

Allergy to chemicals

17%

Dysuria

17%

Conjunctivitis

17%

Autoimmune neutropenia

17%

Hypochromic anaemia

17%

Genital cyst

17%

Body temperature

17%

Body temperature increased

17%

Post-traumatic pain

17%

Tracheal obstruction

17%

Pharyngitis

17%

Eye infection

17%

Gastrointestinal viral infection

17%

Hand-foot-and-mouth disease

17%

Hordeolum

17%

Lower respiratory tract infection

17%

Varicella

17%

Catheter site swelling

17%

Infusion site extravasation

17%

Localised oedema

17%

Cerumen impaction

17%

External ear inflammation

17%

Inner ear inflammation

17%

Tympanic membrane hyperaemia

17%

Hyposideraemia

17%

Initial insomnia

100%

80%

60%

40%

20%

Study treatment Arm

Cohort 2: Age 6 to <24 Months

Cohort 1: Age 24 to 48 Months

Awards & Highlights

Pivotal Trial

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

No Placebo-Only Group

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

Trial Design

4Treatment groups

Experimental Treatment

Active Control

Group I: Part 2: Eteplirsen 200 mg/kgExperimental Treatment1 Intervention

Randomized participants will receive eteplirsen 200 mg/kg once weekly before the selection of the high dose occurs and then will receive the selected high dose once weekly for up to 144 weeks.

Group II: Part 2: Eteplirsen 100 mg/kgExperimental Treatment1 Intervention

Randomized participants will receive eteplirsen 100 mg/kg once weekly before the selection of the high dose occurs and then will receive the selected high dose once weekly for up to 144 weeks.

Group III: Part 1: EteplirsenExperimental Treatment1 Intervention

Participants will receive eteplirsen 100 mg/kg once weekly for at least 4 weeks, followed by eteplirsen 200 mg/kg once weekly for at least 4 weeks.

Group IV: Part 2: Eteplirsen 30 mg/kgActive Control1 Intervention

Randomized participants will receive eteplirsen 30 mg/kg once weekly for up to 144 weeks.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Eteplirsen

2014

Completed Phase 2

~40

0 / 14Eligibility 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) include exon-skipping drugs like eteplirsen, golodirsen, and viltolarsen. These drugs work by skipping specific exons in the DMD gene, allowing the production of a shorter but functional dystrophin protein. This is crucial for DMD patients because the absence of dystrophin leads to muscle degeneration and weakness. By partially restoring dystrophin production, these treatments aim to stabilize muscle function and slow disease progression, offering a significant improvement in quality of life for patients.