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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 SRP-4045, Casimersen
Amondys 45 · 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...
Amondys 45 is an investigational therapy developed by Sarepta Therapeutics for Duchenne muscular dystrophy, a genetic muscle-wasting disorder. It is being studied in patients with DMD duplications eligible for exon 45 skipping. It is a small molecule and is in Phase 2 clinical development.
Amondys 45 is being evaluated for the treatment of Duchenne muscular dystrophy in patients carrying eligible DMD duplications. The Phase 2 study enrolled male subjects aged 6 months and older in the United States. It is investigational and has not been established as a treatment outside of clinical research.
Amondys 45 is developed by Sarepta Therapeutics, Inc., which trades under the ticker SRPT. Sarepta is the sponsor of the clinical program evaluating the drug in Duchenne muscular dystrophy. The company also develops related exon-skipping therapies, including EXONDYS 51 and VYONDYS 53.
Amondys 45 is in Phase 2 clinical development. Its single registered trial, NCT04179409, is a Phase 2 study that has been completed. The drug is investigational and is not approved for commercial use based on the available development information.
Amondys 45 has been studied in one registered clinical trial, NCT04179409. It was a 48-week, open-label, controlled Phase 2 study evaluating Amondys 45, EXONDYS 51, and VYONDYS 53 in subjects with Duchenne muscular dystrophy carrying eligible DMD duplications. The trial enrolled 3 male participants in the United States and is completed.