Casimersen + Golodirsen for Duchenne Muscular Dystrophy

(ESSENCE Trial)

No longer recruiting at 87 trial locations

Overseen By Sarepta Therapeutics Inc., For Clinical Trial Information, Select Option 4

Age: < 18

Sex: Male

Trial Phase: Phase 3

Sponsor: Sarepta Therapeutics, Inc.

Must be taking: Corticosteroids

Must not be taking: Gene therapy

Disqualifiers: Major surgery, Significant illness, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 96 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments, SRP-4045 and SRP-4053, for Duchenne Muscular Dystrophy (DMD), a genetic disorder that causes muscle weakness. The goal is to determine if these treatments are more effective than a placebo for individuals with specific genetic deletions that can be targeted by skipping exon 45 or 53. Participants will receive weekly infusions for up to 96 weeks, followed by an open-label treatment phase. Individuals with DMD who have these specific genetic deletions and stable muscle function might be suitable candidates for this study. As a Phase 3 trial, this represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires that participants stay on a stable dose of oral corticosteroids for at least 24 weeks before starting and throughout the study. The protocol does not specify about other medications, so it's best to discuss with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Earlier studies have shown that casimersen (SRP-4045) was generally well tolerated by people with Duchenne muscular dystrophy (DMD). Most side effects were mild, not serious, and not directly linked to the treatment. The FDA's review of an application for casimersen indicates confidence in its safety.

Long-term safety information is available for golodirsen (SRP-4053). This research shows that golodirsen is generally safe for people with DMD. The FDA has approved golodirsen for patients with certain genetic mutations, further supporting its safety.

Overall, both treatments have demonstrated good safety records in earlier research. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about SRP-4045 and SRP-4053 for Duchenne Muscular Dystrophy because these treatments are designed to specifically target and skip certain exons in the dystrophin gene, potentially restoring a more functional version of the dystrophin protein. Unlike traditional corticosteroid treatments that manage symptoms, these drugs aim to address the genetic root of the disease. This exon-skipping approach is a novel mechanism that could offer a more effective treatment by slowing the progression of muscle degeneration. Additionally, both treatments are administered through weekly intravenous infusions, which may provide a consistent therapeutic effect.

What evidence suggests that this trial's treatments could be effective for Duchenne Muscular Dystrophy?

Research has shown that both SRP-4045 (casimersen) and SRP-4053 (golodirsen) may help treat Duchenne muscular dystrophy (DMD). In this trial, participants will be assigned to different treatment arms to receive either SRP-4045 or SRP-4053. Studies have found that SRP-4045 significantly boosts the process that skips certain parts of a gene, leading to increased production of dystrophin. Dystrophin is a protein that strengthens muscle fibers, and increasing it can improve muscle function in people with DMD. SRP-4053 has been shown to help correct the DMD gene, also resulting in more dystrophin. Both treatments are considered safe and have shown positive results in clinical trials, suggesting they could benefit those with specific gene needs. ^{1 6 7 8 9}

Who Is on the Research Team?

Medical Director

Principal Investigator

Sarepta Therapeutics, Inc.

Are You a Good Fit for This Trial?

This trial is for individuals with Duchenne Muscular Dystrophy (DMD) who have specific genetic deletions treatable by skipping exon 45 or exon 53. Participants must be on a stable dose of corticosteroids, have certain muscle function, and maintain a specific range in the 6-minute walk test. They should not have had gene therapy or other recent experimental treatments.

Inclusion Criteria

I have been on a stable dose of oral corticosteroids for at least 24 weeks.

My lung function is at least half of what is expected for someone my age and size.

I can walk between 300 to 450 meters in 6 minutes.

Exclusion Criteria

Current or previous treatment with any other experimental treatment within 12 weeks prior to Week 1

Presence of other clinically significant illness

I have been treated with SMT C1100 recently and PRO045, PRO053, or PRO051 in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive weekly IV infusions of SRP-4045 or SRP-4053 or placebo for up to 96 weeks

96 weeks

Weekly visits (in-person)

Open-label extension

All participants receive open-label active treatment of SRP-4045 or SRP-4053 for 48 weeks

48 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• SRP-4045
• SRP-4053

Trial Overview The study tests the effectiveness of two drugs, SRP-4045 (casimersen) and SRP-4053 (golodirsen), against a placebo in improving DMD symptoms related to specific genetic mutations. The goal is to see if these drugs can help skip over faulty parts of the gene.

How Is the Trial Designed?

Group I: SRP-4053 Experimental Treatment 1 Intervention

Participants amenable to exon 53 skipping will receive SRP-4053 IV infusions, weekly, at 30 mg/kg for up to 96 weeks in the double-blinded period. This will be followed by an open-label extension period in which all participants will receive open-label active treatment of SRP-4053 at 30 mg/kg/week IV infusions for 48 weeks (up to Week 144 in the study).

Group II: SRP-4045 Experimental Treatment 1 Intervention

Participants amenable to exon 45 skipping will receive SRP-4045 IV infusions, weekly, at 30 mg/kg for up to 96 weeks in the double-blinded period. This will be followed by an open-label extension period in which all participants will receive open-label active treatment of SRP-4045 at 30 mg/kg/week IV infusions for 48 weeks (up to Week 144 in the study).

Group III: Placebo followed by SRP-4045 or SRP-4053 Placebo Group 3 Interventions

Participants amenable to exon 45 or 53 skipping will receive SRP-4045 or SRP-4053 placebo-matching IV infusions, weekly, at 30 mg/kg for up to 96 weeks in the double-blinded period. This will be followed by an open-label extension period in which all participants will receive open-label active treatment of SRP-4045 or SRP-4053 at 30 mg/kg/week IV infusions for 48 weeks (up to Week 144 in the study).

Who Is Running the Clinical Trial?

Sarepta Therapeutics, Inc.

Lead Sponsor

Trials

54

Recruited

34,000+

Published Research Related to This Trial

Golodirsen was found to be well-tolerated in patients with Duchenne muscular dystrophy (DMD), with safety results consistent with previous studies in pediatric patients.

Treatment with golodirsen led to a significant increase in exon 53 skipping and a 16-fold increase in dystrophin protein expression at week 48, indicating its potential efficacy in restoring dystrophin production in muscle tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased dystrophin production with golodirsen in patients with Duchenne muscular dystrophy. Frank, DE., Schnell, FJ., Akana, C., et al.[2023]

Antisense-mediated exon skipping therapy, like the newly approved casimersen (Amondys 45), offers a promising treatment for Duchenne muscular dystrophy (DMD) by restoring the reading frame of dystrophin transcripts, potentially benefiting about 8% of DMD patients.

Casimersen received accelerated FDA approval in February 2021, but its continued use will depend on positive outcomes from an ongoing phase III clinical trial, highlighting the importance of ongoing research for safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Casimersen for Duchenne muscular dystrophy. Wilton-Clark, H., Yokota, T.[2021]

Citations

1. investorrelations.sarepta.com investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-present-new-data-its-neuromuscular-0

Press Release - Investor Relations - Sarepta Therapeutics “As leaders in genetic medicine for neuromuscular conditions, these data expand our understanding of the safety, efficacy and transformative ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02500381

NCT02500381 | Study of SRP-4045 (Casimersen) and ... This is a double-blind, placebo-controlled, multi-center study to evaluate the efficacy and safety of SRP-4045 and SRP-4053.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11048227/

Casimersen (AMONDYS 45™): An Antisense Oligonucleotide ... This article discusses the pathophysiology of DMD, summarizes available treatments thus far, and provides a full drug review of casimersen ( ...

4. mdaconference.org mdaconference.org/abstract-library/casimersen-in-patients-with-duchenne-muscular-dystrophy-amenable-to-exon-45-skipping-interim-results-from-the-phase-3-essence-trial/

Interim Results From the Phase 3 ESSENCE Trial Interim analysis shows casimersen significantly increased exon skipping and dystrophin expression in exon 45 skip-amenable patients at 48 weeks and was well ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34105177/

Safety, tolerability, and pharmacokinetics of casimersen in ... Casimersen was well tolerated in participants with DMD amenable to exon 45 skipping. Most TEAEs were mild, nonserious, and unrelated to casimersen.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9290993/

Safety, tolerability, and pharmacokinetics of casimersen in ... Duchenne muscular dystrophy (DMD) is a rare, fatal, X‐linked neuromuscular disease that is typically caused by mutations in the DMD gene, disrupting translation ...

7. investorrelations.sarepta.com investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-announces-fda-acceptance-casimersen-srp

Press Release - Investor Relations - Sarepta Therapeutics Sarepta Therapeutics Announces FDA Acceptance of Casimersen (SRP-4045) New Drug Application for Patients with Duchenne Muscular Dystrophy ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2021/213026Orig1s000RiskR.pdf

213026Orig1s000 - accessdata.fda.gov This review evaluates whether a risk evaluation and mitigation strategy (REMS) for the new molecular entity, Amondys 45 (casimersen) is ...

9. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/abs/10.1002/mus.27347

Safety, tolerability, and pharmacokinetics of casimersen in ... Casimersen was well tolerated in participants with DMD amenable to exon 45 skipping. Most TEAEs were mild, nonserious, and unrelated to casimersen.