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Label indication AMONDYS 45 is indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 45 skipping. This indication is approved under accelerated approval based on an increase in dystrophin production in skeletal muscle observed in patients treated with AMONDYS 45 [see Clinical Studies ( 14 )] . FDA label
Also known as Casimersen, AMONDYS 45
SRP-4045 · 3 trials · 1 indication
This will be assessed by the comparison of quantification of protein in muscle biopsy tissue by western blot from baseline to 1 year post-initiation of treatment.
This will be measured by capturing and reviewing Adverse Events as defined by CTCAE v4.0.
Adverse event (AE) was any untoward medical occurrence in a clinical trial participant, which does not necessarily have a causal relationship with the investigational drug. AEs also included abnormal physical examination findings (Physical examination were conducted per protocol and any clinically significant abnormal findings were recorded in medical history if pre-existing or addressed as an AE if new or worsening). TEAEs was defined as AEs that started, worsened, or became serious on or after the start of first infusion through 148 weeks. Number of participants with TEAEs were reported.
Laboratory parameters included serum chemistry (hepatic chemistry and renal chemistry), hematology, coagulation, and urinalysis. Number of participants with potentially clinically significant abnormal finding were reported as TEAEs. The Investigator determined whether abnormal assessment results were potentially clinically significant or not. Potentially clinical significance was defined as any variation in assessment results that had medical relevance resulting in an alteration in medical care.
Vital sign parameters included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and body temperature. Number of participants with at least one potentially clinically significant abnormal vital signs findings were reported as TEAEs. The Investigator determined whether abnormal assessment results were potentially clinically significant or not. Potential clinical significance was defined as any variation in assessment results that had medical relevance resulting in an alteration in medical care.
Twelve-lead ECGs were performed at a consistent time of day throughout the study. Electrocardiograms were performed only after the participant was in the supine position, resting, and quiet for a minimum of 15 minutes. The ECG was manually reviewed and interpreted by medically qualified personnel. Number of participants with potentially clinically significant abnormalities in ECG reported as TEAEs were presented here. The Investigator determined whether abnormal assessment results were potentially clinically significant or not.
Standard, 2-dimensional ECHOs were performed at a consistent time of day throughout the study.The ECHO was reviewed and interpreted by medically qualified personnel. Number of participants with potentially clinically significant abnormalities in ECHO were reported.
| Arm | Type | Description |
|---|---|---|
| SRP-4045 | EXPERIMENTAL | 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). |
| SRP-4053 | EXPERIMENTAL | 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). |
| Placebo followed by SRP-4045 or SRP-4053 | PLACEBO_COMPARATOR | 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). |
| AMONDYS 45 | EXPERIMENTAL | This arm will involve the treatment of boys with DMD who have a duplication of exon 45, for which AMONDYS 45 will target skipping of this exon. |
| EXONDYS 51 | EXPERIMENTAL | This arm will involve the treatment of boys with DMD who have a duplication of exon 51, for which EXONDYS 51 will target skipping of this exon. |
| VYONDYS 53 | EXPERIMENTAL | This arm will involve the treatment of boys with DMD who have a duplication of exon 53, for which VYONDYS 53 will target skipping of this exon. |
| Placebo (double-blind dose titration) | PLACEBO_COMPARATOR | Participants with genotypically confirmed Duchenne muscular dystrophy (DMD) characterized by deletions amenable to exon 45 skipping will receive placebo-matching to casimersen intravenous (IV) infusions, once weekly over approximately 12 weeks in the double-blind period. |
| SRP-4045 (double-blind dose titration) | EXPERIMENTAL | Participants with genotypically confirmed DMD characterized by deletions amenable to exon 45 skipping will receive weekly IV infusions of casimersen at four escalating dose levels, each for at least 2 weeks: 4 milligrams per kilograms (mg/kg) during Week 1 to Week 2, followed by 10 mg/kg during Week 3 to Week 4, followed by 20 mg/kg during Week 5 to Week 6, followed by 30 mg/kg beginning at Week 7 and continue over approximately Week 12 in the double-blind period. |
| SRP-4045 (open label extension period) | EXPERIMENTAL | All participants who completed double blind period will be enrolled to receive casimersen 30 mg/kg once weekly, for up to Week 144 in the open label extension period. |
| Name | Type | Description |
|---|---|---|
| SRP-4045 | DRUG | SRP-4045 solution for IV infusion |
| SRP-4053 | DRUG | SRP-4053 solution for IV infusion |
| Placebo | DRUG | SRP-4045 or SRP-4053 placebo-matching solution for IV infusion |
| Amondys 45 | DRUG | This drug is used to target skipping of exon 45 of the dystrophin gene. |
| Exondys 51 | DRUG | This drug is used to target skipping of exon 51 of the dystrophin gene. |
| Vyondys 53 | DRUG | This drug is used to target skipping of exon 53 of the dystrophin gene. |
Inclusion Criteria: * Genotypically confirmed DMD, with genetic deletion amenable to exon 45 or exon 53 skipping * Stable dose of oral corticosteroids for at least 24 weeks prior to Week 1, and the dose is expected to remain constant throughout the study (except for modifications to accommodate cha...
SRP-4045 is an investigational small molecule developed by Sarepta Therapeutics for Duchenne Muscular Dystrophy, a genetic muscle-wasting disease. It is also known as casimersen. It was studied in placebo-controlled Phase 3 clinical trials and is designed for patients whose disease is associated with a confirmed genetic mutation amenable to exon skipping.
SRP-4045 is being developed to treat Duchenne Muscular Dystrophy in male patients. DMD is caused by mutations in the dystrophin gene that lead to progressive muscle degeneration. SRP-4045 is intended for patients with a confirmed mutation amenable to exon 45 skipping, a biomarker-selected population. It remains investigational and is not established as an approved therapy.
SRP-4045 targets dystrophin, the protein missing or defective in Duchenne Muscular Dystrophy. Dystrophin is a structural protein that helps protect muscle fibers during contraction. By targeting dystrophin production, SRP-4045 aims to address the underlying cause of DMD in patients with mutations amenable to exon 45 skipping.
SRP-4045 is being developed by Sarepta Therapeutics, Inc., which trades on the Nasdaq under the ticker SRPT. Sarepta is a biopharmaceutical company focused on precision genetic medicines, including treatments for rare neuromuscular diseases such as Duchenne Muscular Dystrophy.
SRP-4045 has completed Phase 3 clinical development. Two trials are listed for the program, both now completed: a Phase 1 dose-titration and open-label extension study and a Phase 3 study. SRP-4045 remains an investigational agent and is not described as FDA approved in the available program information.
SRP-4045 has been studied in two completed trials. NCT02500381 was a Phase 3 study of SRP-4045 (casimersen) and SRP-4053 (golodirsen) in participants with Duchenne Muscular Dystrophy, enrolling 228 patients across many countries. NCT02530905 was a Phase 1 dose-titration and open-label extension study in advanced-stage DMD patients, enrolling 12 participants in the United States.
Yes. SRP-4045 is the investigational code name for casimersen, the same drug candidate developed by Sarepta Therapeutics for Duchenne Muscular Dystrophy. The Phase 3 trial NCT02500381 refers to the agent as SRP-4045 (Casimersen), confirming that the two names identify the same program.